Biological psychology (year one) Flashcards

Question

Describe the structure and function of the hippocampus

Answer 1

* 3 major layers * Located at medial edge of cerebral cortex, folds back on itself in the medial temporal lobe * Hippocampus means seahorse * Major role in memory (spatial location memory)

Answer 2

■ Limbic system – circuit of midline structures that circle the thalamus ■ – regulation of motivated behaviors – Consists of mammillary bodies, hippocampus, amygdala, fornix, cingulate, septum

Answer 3

* Motor system. * Consists of amygdala, striatum (caudate nucleus + putamen), globus pallidus * Extrapyramindal motor system (output fibres do not cross pyramidal regions of medulla) * Degeneration of nigral-striatal pathway causes rigidity, tremor and slow movement in Parkinson’s disease * Coordination of automated (without thinking) smooth, fluent movement.

Answer 4

* It is the newest part of the cerebral cortex to evolve * Cerebral cortex = largest part of telencephalon, composed of grey matter. Neocortex = largest part of cerebral cortex (90% of cerebral cortex is neocortex in humans). Other part is allocortex (contains hippocampus) * Main difference is that neocortex has six layers – the most developed in its number of layers and organisation of the cerebral tissues (specific to mammals) * Humans have large neocortex ratio, which correlates with complexity of behaviour. For a large neocortex to evolve brain must evolve in size to support it * Central and lateral fissure divide each hemisphere into 4 lobes (frontal, parietal, temporal and occipital) * lobes are not functional units

Answer 5

- Frontal lobe: motor cortex (precentral gyrus) Complex cognitive functions (frontal cortex) - Temporal lobe: hearing and language Complex visual patterns Memory - Parietal lobe: somatic sensations e.g. touch (post central gyrus) Orientation, location of objects - Occipital lobe: Visual processing

Answer 6

- Underwent bilateral medial temporal lobectomy - EEG suggested seizures arose from foci in both left and right temporal lobes. Removal of one medial temporal lobe had proved effective in patients with unilateral temporal lobe focus – thus a decision was made to remove medial portions of both temporal lobes inc hippocampus, amygdala - His generalised seizures stopped, and partial seizures reduced massively. Left surgery well-adjusted, normal perceptual and motor ability, normal intelligence…Memories for events predating surgery intact (more or less), short term memory pretty good too. - BUT…total inability to form new long-term memories. In effect, H.M became suspended in time that day in 1953

Answer 7

 Entered under his left cheekbone, penetrated base of skull behind left eye socket, emerged at the top of the skull  Despite his horrific injury, within minutes Gage was sitting up in a cart, conscious and recounting what had happened  In 1868 Harlow wrote a report on the ‘mental manifestations’ of Gage’s injuries. He described Gage as “fitful, irreverent, indulging at times in the grossest profanity… capricious and vacillating” and being “radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage’.”  The damage to Gage’s frontal cortex resulted in a loss of social inhibitions. Gage’s injuries provided some of the first evidence that the frontal cortex was involved in personality and behaviour.

Answer 8

- Parts which stick out of the cell (axon or dendrite)

Answer 9

Bipolar: 1 dendrite or axon sending action potentials (APs) into the soma 1 axon sending APs out of the soma to the axon terminals

Answer 10

Unipolar: One axon entering the soma. The axon is branched such that APs can travel along the axon without going through the soma directly.

Answer 11

Multipolar: Multiple dendrites sending APs into the soma A single axon sending AP from the soma to the axon terminals.

Answer 12

- Name Golgi: comes from Italian neuroanatomist. Worked out a way of staining these structures for the first time, so they could be observed under a microscope. Now called Golgi method.

Answer 13

- long axons, e.g. motor neuron

Answer 14

- shorter axons project locally e.g. interneuron

Answer 15

In terms of axon length

Answer 16

sensation, integration and action

Answer 17

- to gather and send information from the senses such as touch, smell, sight etc.

Answer 18

- to process all information gathered, thus allowing us to take action.

Answer 19

- to send appropriate signals to effectors Muscles (cardiac, smooth, and skeletal) Glands (e.g. blushing, sweating, etc.)

Answer 20

- E.g. signalling danger through pain | - Goes to both spine (reflexes) and brain (either fearful withdrawal or more considered action)

Answer 21

- Sensory, emotional and cognitive | - Fear can bypass on the thalamus and cortex to cause a response – speeds up responses to danger

Answer 22

This can be a reflex – doesn’t need cognition or emotion – but still involves integration in the spinal cord. Involves: • Sensory (afferent) neuron, unipolar – green. • Integrative (interneuron), multipolar – red • Motor (efferent) neuron, multipolar – blue.

Answer 23

In terms of function, we are interested in whether they feed information towards the CNS, within the CNS or away from the CNS. • Bipolar: e.g. Vision served by bipolar neurons, carrying information from photoreceptors in the retina to the brain. • Unipolar: e.g. Pain served by unipolar neurons, with information gathered by free nerve endings sent to the spinal cord. • Multipolar neurons could either be interneurons (with short axons) that synapse onto other neurons in the CNS, or motor neurons (with long axons) that send information to muscle tissue. • Sensory : towards • Within : interneurons • Away : motor neurons

Answer 24

Sensory neuron: - Vision receptor: often attached to a receptor. Receptors are needed when information is complicated e.g. light captured in the eyes – light is complex to analyse so a neuron by itself would not be able to do that, it needs special receptors (rods and cones in the retina). The neuron translates this complicated information into a simpler neural code or “language” – yes and no, like binary in computers, but the temporal patterns can be complex bursts and we don’t know exactly how neurons code the information they are carrying. - Pain receptor: May not be attached to a separate receptor when the information is more simple, such as pain. Just needs to know if the tissue is damaged or not and the neuron can do this by itself – this type of neuron for pain is called a nociceptor. - In both cases the information is sent to the brain.

Answer 25

- For motor neurons, the cell body (soma) tends to be in the spinal cord, but sometimes in the brainstem.

Answer 26

- In the brain, regions with cell bodies are called nuclei, in the spinal cord are called horns, but in the PNS they are called ganglia. - In CNS, regions with axons are called tracts, but in the PNS they are called nerves.

Answer 27

When “affected” by something, it is something happening to you. - neurons carry information from the body and the outside world into the central nervous system

Answer 28

neurons carry commands from the central nervous system to muscles and organs - “When you “effect” something you are changing it.

Answer 29

- (relay, projection, local) connect and integrate neurons within the central nervous system - Interneurons: when touch something painful (putting foot over the fire), sensation of pain causes automatic withdrawal reflex – occurs via interneurons (not requiring the brain). Have short axons.

Answer 30

- If micro-electrodes are placed inside cell, charge is roughly -70mV (compared to outside the cell) – neuron is polarised

Answer 31

- Selective permeability is important because it keeps cells functioning properly by letting only wanted molecules in and unwanted ones out. In addition to keeping the "bad stuff" out (e.g. bacteria, viruses), selective permeability is essential to the function of our nervous system. Without it, neurons would not "fire".

Answer 32

“Polarisation” is a term meaning charge difference.

Answer 33

Ion is an electrically charged atom or molecule - The membrane controls the environment within and around the neuron - Selectively permeable membrane allows some substances through and blocks the passage of others - Controls polarisation: the difference in electrical charge between the inside and the outside of the neuron - These negatively charged proteins largely explain the balance of the other ions – as the next few slides will show. Give the intracellular and extracellular ion contents - Negative inside, positive outside - K+, Na+, Cl- and chargerd proteins

Answer 34

The membrane potential is partly a result of a balance between 2 opposing forces - Diffusion = molecules distribute themselves evenly through the medium in which they are dissolved. Follows concentration gradient: high to low - Electrostatic pressure = force exerted by attraction or repulsion between charged molecules Positive ions are attracted by negative charges and vice versa

Answer 35

force exerted by attraction or repulsion between charged molecules

Answer 36

- Membrane is impermeable to it | - ve charge provide electrostatic pressure to the other ions:

Answer 37

- Diffusion forces out of cell - Electrostatic pressure forces inside cell - Ions effectively remain where they are, some leak out

Answer 38

- Diffusion forces inside cell - Electrostatic pressure forces out of cell - Ions effectively remain where they are

Answer 39

- Diffusion forces inside cell - Electrostatic pressure attracts inside the cell - Some ions manage to move into the cell

Answer 40

Membrane is only selectively permeable to Na

Answer 41

- It has the same composition as any other cell membrane: fat. This composition is needed because the rest of the body is watery, and fat repels waters. This allows it to maintain integrity and not just get dissolved. - The fat is made of phospholipids. They have a “head” that likes water (outside of membrane) and a “tail” that doesn’t like water (inside). These tails are attracted to each other (and so huddle together) but repel water that is inside and outside the cell.

Answer 42

- Water – because it is so small as a molecule it squeezes though, and it had no charge. Same with O2 and CO2. Ethanol is lipophilic (can use to clean fats). Blood Brain Barrier does not prevent ethanol, which is why it goes to the brain so easily – it’s soluble in the membrane.

Answer 43

- Ions – small molecules with a charge. + means positive charge. This prevents them getting through the bilayer. - Amino acids and glucose are hydrophilic and don’t get through membrane – also too big.

Answer 44

- Proteins (e.g for transport) | - Cholesterol (e.g for rigidity)

Answer 45

``` Transmembrane: Channels (with pore) Integral: Span the membrane but have no pore. Inner membrane: Internal surface of membrane Surface: External surface of membrane ```

Answer 46

Transmembrane: call channels, with pore in the middle. These are the most important for transport. Can also act as pumps. - Important for transport. - Can be ion pumps, channels and carriers

Answer 47

Integral: spans the membrane but has no hole. Proteins called “receptors” don’t have a hole in. Something binds to them (specific – key and lock) – causes chemical change inside.

Answer 48

Inner membrane: These are anchoring points that attach the membrane to internal cell structures. - Attach the cytoskeleton (internal cell structure) to the membrane

Answer 49

Surface: Same but external: sometimes have bit of sugars. Signalling to other cells (like flags). Some types also attach the cell to extracellular matrix (fibres) so that the cells are not just floating around but the cells have structure.

Answer 50

- Pump ensures the cell stays at -70uV - For every 3 Na pushed out, 2 K are moved in. - When you are resting, like now, most of the energy you are using in your body (i.e. the calories you are burning) is to power these pumps. That is how important they are. Every cell uses these but neurons use them to the advantage of communication. - There are also other “leaky” channels (not pumps) which can let K+ through in theory, but in practice K+ stays inside the cell due to electrostatic pressure (positive ion attracts to negative charge inside the cell).

Answer 51

Pumps use energy: they move ions AGAINST their concentration or electrical gradients - The energy is in the form of ATP - Critical for neuronal communication

Answer 52

- Leak K+ channels just stay open all the time. - Voltage gated is sensitive to the potential of the membrane. - Some are ligand-gated – ligand acts as a key (from inside or outside) - Stress: mechanical pressure can open the channels.

Answer 53

Voltage gated, ligand-gated (extracellular ligand), ligand-gated (intracellular ligand), stress activated

Answer 54

- Glia “talk” not only among themselves, but also to neurons. They have receptors for many of the same chemical messengers used by neurons. These receptors enable them to eavesdrop on the neurons and respond in ways that help strengthen their messages. - Communicate chemically (e.g ca+)

Answer 55

Neurons removed from rodents form very few synapses and produce very little synaptic activity - When surrounded by glial cells (astrocytes) synaptic activity increases ten-fold

Answer 56

Mobility, physical support, cleaning

Answer 57

- Support migration during development by providing scaffolding - Support communication of information between neurons (action potentials)

Answer 58

- Form a cellular matrix to hold neural circuits together. | - Provide them with nutrition (e.g oxygen and glucose)

Answer 59

- Clear waste (dead, damaged for neurons e.g), e.g. glutamate is a neurotransmitter and must be cleared from synapses after use, otherwise can be toxic to neurons – possible cause of parkinsons - Contribute to “pruning” unnecessary synapses (especially during brain development

Answer 60

``` Astrocytes • Oligodendrocytes - CNS • Schwann cells – same function as 2 but in PNS • Microglia – important immune function • NG2 glia ```

Answer 61

NG2 glia, or polydendrocytes: precursor cells found in the mammalian central nervous system

Answer 62

- Most numerous type - Also the most complicated – have the most functions. - 9 different types identified so far - One single mature human astrocyte can contact ~2000 neurons and ~2,000,000 individual synapses

Answer 63

ensure that the environment around the neuron is conducive to electrical signals - Support neurons providing the brain with structure (scaffolding) - Removal of debris after injury or neuronal death (scavengers). Apoptosis means neural death. - Neurotransmitter reuptake: promotes efficient signalling. Neurotransmitters are not meant to stay in the synapse so glia will mop these up. - Guide migrating neurons and direct outgrowth of axons during development - Regulate the properties of the presynaptic terminal - Help form the blood-brain barrier

Answer 64

• Nourishment Produce chemicals (ions) needed by neurons Supply glucose, oxygen from blood vessels • Support and guidance Provide physical support (including guiding migration and growth direction during development) • Cleaning and protection Clean up debris (phagocytosis) Neurotransmitter re-uptake

Answer 65

- Astrocytes are critical regulators of neuronal migration, growth and survival during development — consistent with their well-accepted support role. - A classic example is the role of radial glia in neuronal migration early during development. These specialized glia provide a temporary scaffold for the migration of newborn cortical and cerebellar neurons. - Their long radial fibers extend from the ventricular to the pial surface and serve as permissive ‘guidance cables’ for neurons en route to their final target area in the brain. In addition to serving as a structural framework, radial glia provide important trophic support for migrating neurons.

Answer 66

Phagocytosis clears away damaged neuron causing problems such as disrupting chemical processes taking place

Answer 67

Form part of the Blood-Brain Barrier Semi-permeable barrier that controls what passes from the blood to the brain Protects the brain from potentially harmful substances (pathogens, antibodies)

Answer 68

In CNS - Main function: improve message passing between neurons - Neuron with axons – msg passed down – oligos make sure msg passed efficiently by wrapping axon in myelin sheath. - Myelin: fat that provides electrical insulation – makes conduction more efficient, and the thicker the better. More thick = faster transmission.

Answer 69

- Similar function to oligos but in PNS - The Schwann cell is completely wrapped around the axon in the periphery, with just one cell per section, unlike in CNS where one oligodendrocyte can contribute to many sections. - Speed up the processing of the neuron by covering the axon in myelin - Enable axonal regeneration (can only occur in PNS)

Answer 70

- Smallest hence the name microglia. - Come from blood stem cells, unlike all other glia which originate from neural cell progenitors. - main form of defence in CNS. Special treatment from immune system as CNS is so important - immune privileged - meaning CNS is able to tolerate the introduction of antigens or tissue grafts without eliciting an inflammatory immune response. - Limiting the immune response is important because the CNS has limited capacity for regeneration. However, the CNS does not completely lack immune responses as once thought – rather it uses microglia instead. - involved in pruning synapses if no longer needed, making plasticity more effective. When malfunction, associated with neurodegenerative diseases.

Answer 71

- Microglia are thought to play a role in Alzheimer’s - Changes in morphology of glia - The black spots represent areas where microglia have started to kill off neurons

Answer 72

- Glia can be triggered to support the release toxic compounds - This damages vulnerable neuron types

Answer 73

- caused by the malfunction of glia | - Specifically, failure of remyelination by oligodendrocytes

Answer 74

- can be caused by activation of Schwann cells, microglia and astrocytes - Glia release neuromodulators that induce plasticity and cause chronic pain

Answer 75

- Neuron-glial interactions in the spinal cord for the amplification of chronic pain. - Painful injuries such as nerve injury, arthritis, cancer, and treatment (chemotherapy) cause hyperactivity of nociceptors and secretion of glial modulators from their central terminals, leading to the activation of microglia and astrocytes in the spinal cord dorsal horn. - Upon activation, microglia and astrocytes secrete neuromodulators to drive chronic pain by inducing synaptic and neuronal plasticity. - Pre- and postsynaptic neurons can both “listen” and “talk” to microglia and astrocytes. CASP6, caspase-6.

Answer 76

- Post-mortem findings showed reductions in glial cell numbers in some brain regions in patients with mood disorders. - Specific reductions in oligodendrocytes have been reported for the amygdala in major depressive disorder (MDD) - Related research has found a specific disruption of the paranode section where oligodendrocytes contact the neurons, affecting neuronal transmission and emotional processing

Answer 77

- Oligodendrocytes have a role in regulating the development and periodicity of nodes of Ranvier, spaces of bare axon, which contain ion channels critical for action potential propagation along the axon. - Animal studies have shown that stress induces disruption of paranode (where oligos contacts the axons of the neuron). - It’s thought this could lead to disrupted axonal function, namely suboptimal conduction of action potentials along the axon, it’s harder for information to transfer within or between critical brain regions, such as within the amygdala, or between the PFC and amygdala – important because we know that mood is critically dependent on connections between prefrontal cortex and amygdala. May result in abnormal integration of emotional information.

Answer 78

- Back at the start of the 20th century a German psychiatrist and neuropathologist called Alois Alzheimer was caring for a 51-year old patient, Auguste Deter. Auguste presented with a range of behavioural symptoms which are pretty classic signs of dementia, including a loss of short-term memory, cognitive and language deficits, auditory hallucinations, delusions, paranoia and aggressive behaviour, etcetera - At the time this was believed to just be pre-senile dementia, however when she unfortunately passed 5-years after her diagnosis, an autopsy was conducted. During this, Alois found what we now know to be some of the most well-known microscopic and macroscopic markers of Alzheimer’s disease. - Following this point, for quite a while most cases of pre-senile dementia were then classed as Alzheimer’s (unless there was another notable cause) and anything occurring in people that were slightly older was considered to be ‘senile dementia’. - However, in autopsies conducted on people with senile dementia the same pathological markers were found as appear in Alzheimer’s – which led to Alzheimer’s then being classified into two types, early and late onset.

Answer 79

- Most common form of dementia - Two types : the first is early-onset AD (<65 years) (sometimes called familial) and the second is late-onset AD (>65 years) (or sporadic). - The disease slowly progresses, with the changes in the brain starting to occur way before the onset of symptoms- this is why a lot of research is aiming at discovering early markers so we can prevent the disease before it progresses too far. Cognitive decline as we age is expected, however, AD goes one step beyond this and is very debilitating, resulting in a complete loss of independent function and treatments aiming at halting progression once symptoms show aren’t working, which is why we need to find something to target before the disease has progressed. - Currently the treatments offered aim at improving cognition through increasing the neurotransmitters involved in memory and attention, however these are purely symptomatic treatments and do not halt the progression of the disease. No new drugs have been approved since 2003.

Answer 80

``` Early symptoms  Short-term memory loss Advanced symptoms  Long-term memory loss  Confusion  Language impairment  Personality changes  Delusions  Progressive disorientation and visuo-spatial deficits  Depression and anxiety (commonly occur) ```

Answer 81

On the macroscopic level you can see that as AD progresses, there is an increasing amount of cortical atrophy (shrinkage) that occurs due to the neuronal death which is why the sulci (troughs) in the brain become enlarged.

Answer 82

- On the microscopic level, histological staining techniques reveal the classic pathology seen in AD – the same things Alois Alzheimer found.

Answer 83

- amyloid (senile) plaques, which are made up of peptides called Amyloid- (A). - This comes from the breakdown of a protein (amyloid precursor protein), which should be broken down to make peptides which are neuroprotective, however it can also be broken down through another pathway and form AB. - In AD it’s thought that there is an increase in the second pathway, and we can’t clear all the AB so it will build up and aggregate to form these plaques. It’s thought that AB is toxic because of it binding to neuronal receptors and causing synaptic dysfunction

Answer 84

- which accumulate within the neurons. - These are made up of a protein called Tau, which when healthy helps with transporting things like neurotransmitters down to the synapses, but when it undergoes the change it does in AD, then it causes synaptic dysfunction again.

Answer 85

These act as the immune cells in the brain and will usually destroy any pathogens/problematic build ups of protein- in this picture they are surrounding the amyloid plaques (green).

Answer 86

- inflammation in the brain is bad because our CNS neurons don’t regenerate - There were clear markers of inflammation in AD patients found in both the brain and the CSF and microglia were found to be in what is known as an activated state – all clear signs of inflammation. - Inflammatory factors are shown to increase in both the brain and cerebrospinal fluid (CSF) of AD patients - Increase in activation of microglia – our main form of immune defence in the CNS. Express receptors responsible for detecting foreign pathogens Release inflammatory factors Express receptors to detect inflammatory factors

Answer 87

- normally microglia exist in what was considered to be an inactive state, otherwise known as ramified microglia and are located in the parenchyma of the healthy brain. - Although it was called an inactive state, it has been demonstrated that the processes of ramified microglia constantly survey the environment for chemical signals. - Alterations in this environment lead to rapid morphological changes, as well as upregulation of receptors necessary for the detection of inflammatory factors. These changes lead to the microglia becoming an amoeboid shape instead, which then allows them to go and engulf any harmful proteins/pathogens/dead neurons in a process known as phagocytosis.

Answer 88

When they are in the amoeboid shape, they can be both neuroprotective or neurotoxic.

Answer 89

- Part of the role of neurons is to maintain the ramified microglial state through expression of proteins on their membranes and release of signalling molecules. The activation of microglia is normally restricted to stop too much neuronal damage. - Neurons will express/release chemical ‘OFF’ signals constitutively (at a constant level) to keep the microglia from activating. However, ‘ON’ signals, will be produced on demand to instigate microglial activation – this occurs when neurons are stressed or damaged.

Answer 90

- The reason this occurs is because in AD, amyloid-β (Aβ) which makes up the plaques has been shown to activate a cascade of signals that results in something called opsonization (which means targeting something for destruction by immune cells). - This signal is detected by scavenger receptors microglia processes and results in them becoming activated and migrating towards the plaques, so they surround them and engulf amyloid via phagocytosis. - If you ablate the expression of the scavenger receptors responsible for detecting opsonization, this results in an increase in the deposition of Aβ, and if you up-regulate the expression of the receptors it results in increased clearance of the plaques.

Answer 91

- One of the receptors expressed on microglia, called TREM2, is able to detect the amyloid plaques. - Genetic mutations in this receptor which reduce its activity results in a reduction in the ability of the microglia to engulf amyloid-β and enhances the expression of pro-inflammatory factors. This leads to accelerated accumulation of amyloid and neurotoxicity (due to the inflammation and the increased amyloid). - However, if you increase the amount of TREM2 expressed by microglia, it increases the responsivity of the microglia, so it takes less time for the microglia to be activated and for phagocytosis to occur. - Since the phagocytic activity of the microglia is increased, the amount of amyloid plaque decreases. - Which means that fewer microglia are activated because the other microglia are able to work quicker. This reduces inflammation and the amount of amyloid plaque that can be seen, which was correlated with improvements in the memory deficits seen in the mouse model the team used.

Answer 92

- Paul Edison (2018) detected a significant 20-35% increase in microglial activation in AD patients, as we would expect. A significant 2-fold increase of amyloid was also found in the same cortical areas. - Another study was aiming to see if there is correlation between cognitive impairment and the pathology. So they used a test called the mini-mental state examination (MMSE) which is a diagnostic tool used to measure cognitive impairment. They found that scores on the MMSE in the AD patients were inversely correlated with the cortical microglial activation, but not amyloid load. So this may support the idea that microglia are neurotoxic (i.e. cause neuronal damage) as scores worsen the more activation there is.

Answer 93

- During this the microglia release pro-inflammatory factors which are partly responsible for the neuronal damage/death. - In doing so, the neuron will die causing it releases factors that act as ON signals for the microglia, which further activate the microglia. This results in a loop of continuing neuronal damage which is very detrimental.

Answer 94

- The typical resting membrane potential inside the neuron is -70 mV - However this can influenced by incoming signals from other cells which can either: - Further polarise the cell (more negative) this inhibits the likelihood of an action potential occurring - Else it can depolarise the cell (make it more positive, i.e., towards neutral) which is excitatory and increases the chance of the cell generating an action potential.

Answer 95

- Post synaptic potentials travel across the neuron almost instantaneously (rapid) - But as they travel they decrease in size (decremental).

Answer 96

If the cell receives excitatory input it will depolarise. - If the membrane potential at the Axon Hillock (red square) achieves the threshold of excitation (commonly -50 to -55 mV) the cell will fire. - However, remember that the incoming signals can only travel short distances before they expire (decremental)

Answer 97

- If the cell receives inhibitory input it will hyperpolarise to become even more negative. - If the inside of the cell is more negative you’ll need a bigger stimulus to reach the threshold. - Therefore the cell is inhibited from firing by hyperpolarisation

Answer 98

* The resting potential of post-synaptic cell is polarised (-70 mV). * Cells are usually contacted by many incoming PSPs. * Each PSP could have excitatory or inhibitory influences (usually many of each), by depolarising or hyperpolarising the post-synaptic neurone (respectively). * The effect of these PSP’s transmit across the neuron decrementally. * The balance between excitatory and inhibitory input (the net effect) determines whether an action potential fires * If the net effect transmitted to the axon hillock results in depolarisation to the threshold of excitation then an action potential will fire.

Answer 99

When the integration of inputs achieves the threshold of excitation at the axon hillock, it initiates the generation of an action potential (AP). The AP itself is described according to various components or phases: • Depolarisation: Na+ channels open, influx of Na+ into cell. • K+ channels open, K+ begins to leave cell. • Peak : Na+ channels begin to close, K+ channels still open. • Repolarization: Na+ stops entering cell, K+ ions move out. • Hyperpolarization: K+ channels start to close but some K+ ions continue to move out of cell.

Answer 100

This means that you need a non-decremental way to send information long distances. - AP are large swings to opposite polarity - Non-decremental so able to carry the original signal for long distances

Answer 101

* Action potentials are able to transvers large distances without losing the integrity of the signal (the original large swing in polarity is maintained). * This is due to a cascading effect whereby the rapid depolarisation at the axon hillock leads to achievement of the threshold of excitation in the next section of the axon and this continues down the length of the axon.

Answer 102

- Myelinated axons (up to 150 m/s) | - Non-myelinated axons (0.5-10 m/s)

Answer 103

- Pre-synaptic terminal buttons to post-synaptic soma, axon or dendrites - Axon to dendrites : axo-dendritic - Axon to soma : axo-somatic - Axon to axon : axo-axonic

Answer 104

* Electrical synapses are the result of a narrow gap between the pre- and postsynaptic neurons known as a gap junction. * The close proximity (e.g., 4 nm) means the cytoplasm of the two cells are interconnected * This permits electrical signals (and even small molecules) to pass directly from one cell to the next. * This system is FAST (faster than chemical synapses) and BIDIRECTIONAL.

Answer 105

- Electrical synapses in the cerebral cortex allow each network of inhibitory neurons to fire in a highly coordinated way - They may relate to rhythmic activity in the cortex. - The high speed of electrical synapses transmission means they are important for reflexive processes. - A downside of electrical transmission is that there is no opportunity for ‘gain’ i.e., a small signal cannot bring about a large response.

Answer 106

- This method of transmission depends on the release of chemicals from presynaptic cell, which are received and have an effect on post synaptic cell. • In chemical synapses the pre- and post-synaptic membranes are divided by the synaptic cleft (20 nm wide). • The post-synaptic membrane contains receptors that can receive the chemical transmitters that will be used to communicate from the pre-synaptic cell.

Answer 107

Neurones contain bubble like structures that are filled with chemicals called vesicles. - The AP stimulates the influx of Ca2+, which causes synaptic vesicles to: • Attach to the release sites • Fuse with the plasma membrane • Expel their contents into the synaptic cleft. These chemicals can act as a form of transmission or communication by affecting the post-synaptic neurone.

Answer 108

• NT receptors are membrane spanning proteins. • The part exposed to the extracellular space recognises and binds the transmitter to bring about a function that has an effect on the target cell. • There are different types of receptor. 2 of the most common: 1. Ligand-gated ion channels - direct 2. G-protein-coupled receptors - indirect

Answer 109

According to the effect on postsynaptic cell, synapses can be: - Excitatory (+ e.g., Na+, Depolarising) - Inhibitory (e.g.c Cl-, hyperpolarising) - Depending on the type of ion channel which opens, the postsynaptic cell membrane becomes either depolarised or hyperpolarized. • This decreases or increases the likelihood of the receptor neurone firing with an AP. • You recognise this because, once again, we are talking about Post synaptic potentials.

Answer 110

A neurotransmitter (NT) is a chemical released by the presynaptic neuron to bring about an effect in the post-synaptic neurone. A NT: - Must be produced within a neuron - Must be released when the neurone is stimulated - When released, it must act on a post-synaptic receptor and cause a biological effect. - Once released it must be inactivated. - If the chemical is artificially applied on the post-synaptic membrane, it should have the same effect as when it is released by a neuron.

Answer 111

* Amino acids e.g glutamate, GABA, aspartate * Monoamines e.g dopamine, epinephrine, norepinephrine * Acetylcholine * Unconventional neurotransmitters e.g soluble gasses (nitric ocide), endocannabinoids (anadamide)

Answer 112

- Obtained from proteins we eat or synthesized (GABA from glutamate) - Found at fast-acting direct synapses - Glutamate : most prevalent excitatory neurotransmitter (AMPA and NMDA) - GABA : most prevalent inhibitory NT - Balance of arousal and quiesence

Answer 113

- Large molecules (3 to 40 amino acids) - Over 100 identified, loosely grouped - E.g pituitary peptides, brain-gut peptides

Answer 114

- Receptors cannot withstand exposure to neurotransmitters constantly - If they are overexposed to NT all the time their ability to respond is impaired (desensitise) - Therefore, a mechanism is required to clear unused NT from the cleft to prevent residual activation - Enzymatic degradation - Reuptake - Diffusion - glia

Answer 115

- Breakdown of NT into parts which do not cause activation in post synaptic membrane - E.g acetylecholine broken down into acetate and choline by acetylecholinesterase

Answer 116

- NT molecule is reabsorbed by presynaptic neuron and repackages into vesicles for reuse

Answer 117

- It was once believed that each neurone synthesises and releases only ONE neurotransmitter - Now it is known that many neurones contain more than one neurotransmitter - Usually one small NT and a neuropeptide

Answer 118

- Agonists increase or promote activity | - Antagonists decrease or inhibit the activity

Answer 119

Zygote (at fertilisation) – 2 blastomeres – 4 blastomeres – morula (72 hours later)

Answer 120

Morula – blastula – trophoblast (embeds in endometrium)

Answer 121

Layers in the embryonic disk contain nervous system cells (ectoderm, mesoderm, endoderm) : collectively neural plate

Answer 122

First observable development of the nervous system is the induction of the neural plate. - 3 weeks after conception, patch of the ectoderm becomes distinguishable as neural plate. - The neural plate develops to form: - neural groove - neural tube

Answer 123

- The anterior end of the neural tube develops 3 swellings that become the forebrain, midbrain and hindbrain (7 weeks - Day 40) - Neural proliferation: At this stage rapid cell division occurs in the ventricular zone of the neural tube (nearest the ventricle).

Answer 124

- Forebrain : ventricle = lateral, subdivision = telencephalon, principle structure = cerebral cortex/ basal ganglia/ limbic system - Midbrain : cerebral aqueduct, subdivision = mesencephalon, principle structure = tectum, tegmentum - Hindbrain : ventricle = fourth, subdivision = metencephalon, myencephalon, principle structure = medulla oblongata

Answer 125

- Once the cells have been created in the ventricular zone they migrate to appropriate location - During this process they are still immature neurones (no dendrites or axons). - Glia make scaffolding for migration - After migration, cells aggregate to form various neural structures.

Answer 126

- Once neurones aggregate in desired location differentiation occurs. - Axons and dendrites may begin to grow as cells differentiate depending on purpose and location

Answer 127

- During gestation, more neurones are produced than required (50%) - ‘Superfluous’ cells die - This can be • Pre-programmed (apopstosis) • Synaptic rearrangement: unnecessary connections die (necrosis)

Answer 128

-By 20 weeks the brain is about 5 cm long and it has the basic shape of a mature brain

Answer 129

- At birth: 350-400 g -Adult: 1300-1400 g - Much of the growth happens in the first 2 years - This increase in size is NOT due to increase in number of neurones - Three other kinds of growth • Synaptogenesis • Myelination • Increasing branching of dendrites

Answer 130

- Synaptogenesis is important because the number of connections between neurones is assumed to be an indicator of the brain function or capability. - There is a rapid increase in synaptogenesis in the cortex after birth. - But there are differences between regions (i.e., in visual and auditory cortices proliferate at 4 months whereas frontal cortex develops more at 2 years) - Many synapses that form early in development are eventually lost; overproduction of synapses in the young brain may contribute to greater plasticity with relevance for learning

Answer 131

* Myelination increases the speed of axonal conduction and parallels functional development * Myelination of sensory areas occurs in first few months * Then myelination of motor areas * Myelination of prefrontal cortex continues into adulthood

Answer 132

* Rapid process | * Changes can be observed in seconds

Answer 133

* Pruning: The selection of the pruned terminal arbours follow the "use it or lose it" principle seen in synaptic plasticity. * This means synapses that are frequently used have strong connections while the rarely used synapses are eliminated * Pruning is carried out by microglia

Answer 134

- Most experiences are time dependent: the effect of a given experience on development depends on when it occurs during development - Leads to the concept of early development as a ‘window of opportunity’ - Sensory deprivation: animals reared in the dark have fewer synapses in visual areas and as adults have problems perceiving depth. - Enrichment: thicker cortices with more dendrites and more synapses per neurone

Answer 135

1- Autistic individuals spend less time looking at faces and remember faces less well Research has shown that brain areas that respond to faces (fusiform gyrus) are less active 2- Mirror neurones: these neurones fire when you see somebody performing an action They help one understanding the intentions of others. Children with autism have deficient mirror neurone function

Answer 136

- Intellectual disability and heterogeneous pattern of abilities and disabilities (similar to autism) - In many aspect opposite to autism: Sociable, empathetic and talkative - Very good linguistic and musical abilities - Serious cognitive deficits: attention, spatial abilities. Terrified of apparently mundane - Impaired spatial abilities and underdeveloped parietal and occipital cortices; this appears to be due to a major mutation in chromosome 7

Answer 137

``` Contrast X-rays • cerebral angiography • Computer Tomography (CT) • Magnetic Resonance Imaging (MRI) • (Functional) MRI • Positron Emission Tomography (PET) • Electroencephalography (EEG) • Magnetoencephalography (MEG) • Transcranial Magnetic Stimulation (TMS) ```

Answer 138

- Electroencephalography, (EEG) is the measurement of electrical activity from the brain using electrodes located on the scalp. - Electrodes measure voltage fluctuations which directly result from the flow of ions across cell membranes of neurons and explain EEG

Answer 139

- Electrodes: metal contact disc of 0.7-1.0 cm diameter (Ag/AgCl, Au, Sn) - Electrodes connect to a powerful amplifier, which also digitizes signals and conveys them to a processing computer.

Answer 140

Action Potentials: - Rapid, transient, all-or-none swing in polarity of ~100mV and a duration of 1ms that propagate from the body to the axon terminal of a neuron. - Not sufficient to be recorded by EEG electrode Post Synaptic Potential: • Action Potential reaches the axon terminal and releases neurotransmitter. • Neurotransmitter binds to the receptor on the postsynaptic neuron which becomes (de)polarised. • This causes a voltage change (PSP) which can last tens or even hundreds of milliseconds and may summate with other PSP’s nearby at similar time. The source of EEG recorded activity

Answer 141

* Pyramidal neurons are spatially aligned and perpendicular to the cortical surface. * EEG signals stems from synchronous activity of large (~1000s) groups of neurons close to each other and exhibiting similar patterns of activity * Thus, EEG mainly represents postsynaptic potentials of pyramidal neurons close to the recording electrode. * Termed: Local field potential

Answer 142

* Ongoing brain activity is characterised by fluctuating of local field potentials (measured as changes in voltage) which rises and fall in a rhythmic fashion over time * This is what we measure and observe when using EEG * Each line on an EEG recording represents the oscillating voltage occurring underneath the electrode. * By using many electrodes across the head we can pick up an idea of the different electrophysiological activity occurring across the brain.

Answer 143

* Brain-computer interfaces are direct pathways of communication between the brain and some external device. * They can take many forms depending on hardware and software. * External/or internal brain sensor or stimulator. * Connected to hardware (e.g., machinery, neuro-prosthetics), or computer software. * Limitless clinical and commercial applications

Answer 144

- Whenever we think, move, feel or remember something, specific groups of neurons, often grouped together in particular regions of the brain, are activated. - This activation forms a pattern, and the dynamics of the pattern can be studied using signal processing methods. - Brain communication via action potentials relies on post-synaptic potentials which cause a local field potential. - This LFP activity can be detected, and even interpreted in virtually real-time, in order to command output -or receive input - from an external device of some kind.

Answer 145

- BCI bypasses the brain’s normal pathways, e.g., via peripheral nerves, muscles or sensory organs, to bring about an application.

Answer 146

- OUTPUT BCIs = devices that convert human intentions in the form of electrophysiological signals to overt device control. E.g., neuroprosthetic. • Electrodes capture electrophysiological activity of motor cortices and transmit to a computer in real-time (or close to). • This signal is decoded according to a complex machine learning algorithm which is tailored to the patients brain patterns. 3.The software estimates the most appropriate action and send the command to the neuroprosthetic to perform the action (e.g., grasp fist with X degree of force).

Answer 147

Explain input BCIs and give an example - INPUT BCIs = devices that translate external stimuli such as light or sound into internally perceived visual or auditory perceptions Most common example of sensory prosthetic is the cochlear implant. Patients lack cochlear hair cells that transduce sound into neural activity. - Example : cochlear implant • Sound processor behind the ear captures sound and turns it into digital code. * This is transmitted to the internal implant. * The implant converts the digitally-coded sound into electrical impulses and sends them along an electrode array in the cochlea (the inner ear). * The implant's electrodes stimulate the auditory nerve, which then sends the impulses to the brain where they are interpreted as sound.

Answer 148

``` • Non-Invasive BCIs typically include equipment that can sense changes in brain activity in (or close to) real time. • Essentially this means EEG. • Comfortable • Wireless systems available. • Lo-cost (relatively speaking ) • produce poor signal resolution o (skull interferes with signals) ```

Answer 149

ECoG (Electrocorticography) is a electrode array that can be implanted on top of relevant cortex (e.g., motor regions) to record activity from specific parts of the brain. The advantage is that the signal is recorded before it is diffused by the skull (subdural) Not signal taken from within the brain parenchyma itself. - Micro electrodes involve a tiny array of needle electrodes actually inserted into brain tissue (e.g., motor cortex) to record field potential directly as they occur. Most accurate – but more risky

Answer 150

● Decoding the brain activity that underpins intention of movement is a huge research target. This has clinical implications (paralysis, locked-in syndrome) and also leisure and commercial applications (e.g., gaming etc.) * μ–rhythm (mu) is a distinctive rhythmic electrophysiological activity that we observe over the motor cortices. * Research shows that movements or imagination of movements suppress the μ–rhythm of the contralateral motor cortex. * This activity and supression phenomenon occurs even in people who have a compromised peripheral motor system (e.g., spinal-cord injury etc. ) * This makes μ–rhythm activity a research target for BCI‘s, aiming to control a prosthetic which is designed to imitate or replace motor capability.

Answer 151

* A brain disorder characterised by cell death. * Mechanisms likely include dysfunctional neurotransmission of dopamine in specific brain regions. * When a significant proportion of dopaminergic motor neurons die we see a huge drop in dopamine levels. This inhibits the ability for remaining neurons to generate and transmit a signal which causes characteristic Parkinsonian gait and symptoms such as tremors.

Answer 152

* Again, AD represents a neurodegenerative brain disorder characterised by cell death. * Causes are not fully known, but likely include genetic and environmental factors. * Like with PD, cell death may be due to complex changes neurotransmission systems. * Cognitive decline appears in patients before extensive neuronal loss. Therefore, synapse dysfunction is likely to be an early cause.

Answer 153

* ASD is a diverse neurodevelopmental condition, arguably defined by two core symptoms: social deficits and stereotypical behaviour. * An imbalance between excitation and inhibition in neocortical areas has been proposed as a key process in ASD pathogenesis (Baudouin et al. 2012). * Synaptic dysfunction in ASD could be caused by alterations of glutamate receptors. Potentially due to underlying genetic cause

Answer 154

* Chronic stress leads to dysregulation of the HPA and (usually) elevated levels of basal cortisol * Cortisol increases glycemia (blood glucose level) and amino-acids in the blood * Glucose and amino-acids stimulate secretion of insulin from b-cells of Langerhans islets to transport the glucose into cells (therefore, high insulin levels in the blood) * Due to too much of glucose in the cells, the inner part of insulin receptors undergoes molecular changes making them less effective, and glucose cannot enter cells in spite of high insulin

Answer 155

• Lipid insoluble: • proteins and peptides (e.g., insulin) • derivates of amino acid tyrosine (e.g. thyroid hormones) • lipid insoluble hormones are chains of amino acids (valine, o leucine, proline…) • proteins (>100 amino acids) or peptides (<100 amino acids) * Lipid soluble: have a common precursor cholesterol * (steroid hormones, e.g., aldosterone, cortisol, testosterone…) * Cholesterol is a fat-like molecule, abundant in cell membranes.

Answer 156

- A chemical agent secreted by a group of cells and acting at a distance from the site of origin (a gland, tissue). • Endocrine hormones: secreted by specialised cells or gland into the circulating blood (e.g., insulin, corpus luteum) • Neuroendocrine hormones: secreted by neurons into circulating blood (e.g., hypothalamic releasing hormones) • Cytokine hormones: peptides secreted by tissues (e.g., leptin)

Answer 157

• A key and the lock: hormones can affect a cell only if cell has a receptor that fits. • Hormone receptors are large proteins, and a cell usually needs to have 2000 or more receptors to be engaged by a hormone • Down-regulation and up-regulation of receptors is a tool to regulate bodily response to hormones

Answer 158

• Via ion channels (rare) and G protein-linked receptors (peptides, proteins) • Via binding to intracellular receptors and acting on DNA (steroids) • Via direct actions on the cell nucleus (thyroid hormones)

Answer 159

A receptor on outer side of membrane is activated by a hormone. It causes activation of alpha unit of G protein (GDP). Alpha unit detaches from beta and gamma units and activates various intracellular enzymes (adenylyl cyclase, phospholipase C and several other).

Answer 160

A steroid freely passes the cell membrane and binds to receptors in the plasma. The hormone-receptor complex binds to hormone-response element strand of DNA (promoter).

Answer 161

- Thyroid and adrenal medullary hormones are derived from amino acid tyrosine. The hormones pass the cell membrane via carrier channels and enter the nucleus. There is a thyroid receptor on hormone sensitive element of some genes causing transcription of DNA into mRNA. - Tyrosine-based hormones can activate or deactivate genes and lead to synthesis of new proteins

Answer 162

* Hypothalamic releasing hormones: top level of regulation, growth * Anterior pituitary hormones: second level of regulation * Posterior pituitary hormones (vasopressin, oxytocin) – smooth muscle contractions * Thyroid hormones (thyroxin T4, triiodothyronin) - metabolism * Adrenal cortex hormones (aldosterone, cortisol, androgens) – metabolism, stress * Adrenal medulla hormones (adrenaline, noradrenaline) – stress, emotions * Pancreas (insulin, glucagon) – maintaining glucose level * Sex hormones (estrogens, progesterone, testosterone) - reproduction * Gastro-intestinal peptides (CCK, leptin, ghrelin, NYP): eating behaviour

Answer 163

``` • With the brain stem and reticular formation > autonomic system • Anterior thalamus and limbic system • Hypothalamic infundibulum area (Endocrine control) ```

Answer 164

• Thyrotropin-releasing hormone = TRH stimulates secretion of thyroid-stimulating hormone in anterior pituitary • Gonadotropin-releasing hormone = GnRH stimulates secretion of LH and FSH in anterior pituitary • Corticotropin-releasing hormone = CRH stimulates secretion of adrenocorticotropic hormone in anterior pituitary • Growth hormone-releasing hormone = GHRH stimulates secretion of growth hormone in anterior pituitary • Growth hormone-inhibitory hormone = somatostatin Inhibits secretion of growth hormone in anterior pituitary • Prolactin-inhibitory hormone – PIH (dopamine) inhibits secretion of prolactin in anterior pituitary

Answer 165

• Thyrotropin-releasing hormone = TRH stimulates secretion of thyroid-stimulating hormone in anterior pituitary • Gonadotropin-releasing hormone = GnRH stimulates secretion of LH and FSH in anterior pituitary • Corticotropin-releasing hormone = CRH stimulates secretion of adrenocorticotropic hormone in anterior pituitary • Growth hormone-releasing hormone = GHRH stimulates secretion of growth hormone in anterior pituitary • Growth hormone-inhibitory hormone = somatostatin Inhibits secretion of growth hormone in anterior pituitary • Prolactin-inhibitory hormone – PIH (dopamine) inhibits secretion of prolactin in anterior pituitary

Answer 166

stimulates body growth, cell multiplication and differentiation 2. Adrenocorticotropic hormone – ACTH stimulates secretion of glucocorticoids and androgens in adrenal cortex 3. Thyroid stimulating hormone – TSH stimulates secretion of thyroid hormones Follicle-stimulating hormone – FSH stimulates development of ovarian follicles and spermatogenesis in testis 4. Luteinizing hormone – LH causes ovulation and stimulates the corpus luteum; stimulates secretion of estrogens and progesterone in ovaries; stimulates testosterone in testis 5. Prolactin – PRL stimulates milk secretion and development of mammary glands

Answer 167

``` • Vasopressin (arginin-vasopressin, antidiuretic hormone) primarily in the supraoptic nucleus • Oxytocin primarily in paraventricular nucleus ```

Answer 168

- Prolactin is a hormone secreted in anterior pituitary. It is a hormone promoting secretion of milk in lactating mothers. - Prolactin in non-lactating female is maintained at a low level, about the same level as in males. The inhibition of secretion of this hormone is mediated by the hypothalamic prolactin inhibitory hormone. However, after giving birth to a baby the level of estrogens and progesterone falls sharply since these two hormones were secreted in the placenta. - A decreased level of estrogens and progesterone postpartum unblocks the secretion of PRL, and PRL suppresses the secretion of the gonadotropic releasing hormone in hypothalamus. - Therefore, a lactating female will have very low levels of estrogen and progesterone. Bursts of prolactin secretion are triggered by nursing, by mechanical stimulation of nipples during feeding the baby. • PRL facilitates parenting behaviour and monogamy

Answer 169

- PRL can cross blood-brain barrier and brain has PRL receptors in hypothalamus and other regions. - PRL has anxiolytic effects. - PRL counteracts effects of stress hormones – glucocorticoids - PRL improves mood after parturition and opposes detrimental effects of stress during pregnancy on depressive-like behaviour of offspring (Smith et al., 2004)

Answer 170

- Formula-feeding mothers had greater scores of depression and anxiety compared to breastfeeding mothers. The plasma level of PRL negatively correlated with perceived stress in breastfeeding group. Studies like these point to the importance to PRL as a hormone protecting mothers from depression in weeks after giving birth and it is a good example of anxiolytic effects of PRL.

Answer 171

- Released from posterior pituitary • A peptide (9 amino acids) causing decreased secretion of water (antidiuresis) via producing water channels (aquaporins) in collective ducts of kidneys • The latency of antidiuretic effect is 5-10 min. • The signals for secretion of vasopressin: increased concentration of solutes (ions) due to low water intake or due to loss of fluids (detected in the atria of the heart). • The osmolality of fluids is detected in hypothalamus and in the third ventricle (stria terminalis of organum vasculorum). • Vasopressin is a powerful vasoconstrictor agent: increases blood pressure

Answer 172

• Osmoreceptor cells in supraoptic nc. And stria terminalis of organum vasculorum shrink in response to increase of plasma osmolarity (plasma sodium concentration) • Shrinking causes action potentials in supraoptic nucleus which stimulate release of vasopressin from secretory granules in posterior pituitary • Dryness in the mouth, dehydration, and loss of fluids stimulate sensation of thirst

Answer 173

* Prairie voles form monogamous bonds, in contrast to Montana voles which are polygynic/polyandric * Prairie voles will create monogamous bonds with one partner if they can spend time together, groom and touch each other. * Mono- and polygamous voles differ in their ability to increase production of oxytocin and vasopressin during the familiarisation period. Further, monogamous volves activate the dopaminergic reward system (first D2 receptors, later D1 receptors) along with the two hormones. * Monogamous prairie voles showed stronger expression of vasopressin and OT receptors in nucleus accumbens than polygamous volves.

Answer 174

- Released from posterior pituitary  Also a small peptide (9 amino acids) causing contractions of smooth muscles in the breast during milk ejection and in uterus during parturition  The amount of oxytocin increases during parturition. The signal for release of oxytocin comes from the increased pressure on uterine cervix during later stages of parturition.  Milk ejection: suckling stimulates the nipple of the breast and the somatosensory signals are being transmitted to hypothalamic supraoptic and paraventricular nuclei. Oxytocin stimulates the myoepithelial cells around the alveoli of milk glands.  Oxytocin is a hormone of social affiliation: OT increases both in men and women after the birth of a baby – promotes parenting

Answer 175

* T3 (triioidothyronine) and T4 (thyroxine) * cleaved from a colloid (thyroglobulin) making up the bulk of thyroid gland. * Widespread effects throughout the body: * increased metabolism * increased heart rate and strength * increased respiration * growth, CNS development * Regulation: TRH and TSH in a form of a double negative -feedback loop

Answer 176

• Hypersecretion of thyroid hormones: • Excitation of CNS, increased speed of cognitive at the cost of being disorganised • Nervousness, anxiety, restlessness, impaired concentration, worries, o paranoia, depression, manic episodes in severe thyrotoxicosis • Hyposecretion of thyroid hormones: • Cognitive - cognitive impairment, lack of concentration, memory deficits, psychomotor slowing • Psychiatric - delusions, hallucinations, depression, impaired sleep, apathy

Answer 177

* Animal experiments showed presence of thyroid receptors in many brain areas, especially in phylogenetically younger regions. * Both T3 and T4 hormones are found in the cerebral cortex. * Thyroid hormones increase the turnover of serotonin (5-hydroxitryptamin, 5-HT) in brain stem nuclei, and hypothyroid states show a decrease in 5-HT production. * 5-HT and noradrenaline are the main mood regulatory systems, with depression showing a decreased serotoninergic activity

Answer 178

- impaired verbal and non-verbal development in children if mothers showed severe hypothyroidism in gestation week 13.

Answer 179

* Secreted from beta-cells of Langerhans islets in pancreas * Hormone of energy abundance: allows transport of glucose into cells in the presence of high blood glucose level, formation of glucose stores (glycogen) and fat stores (adipose tissue), and supports proteosynthesis * Secretion initiated in the presence of * high blood glucose, amino acids, * parasympathetic stimulation, and * gastrointestinal hormones * gastrin, CCK and other factors * CCK = cholecystokinin

Answer 180

* Type 1 diabetes: lack of insulin secretion * Type 2 diabetes: decreased sensitivity of insulin receptors, known as insulin resistance * Psychological stress can potentiate insulin resistance via cortisol (stress hormone) * insulin resistance often manifests in weight gain, obesity, fasting hyperglycemia and hypertension, poor sleep, reduced memory * Exercise, caloric restriction, weight reduction can often help in Type 2 diabetes with no medication required

Answer 181

• Insulin penetrates the blood-brain barrier and brain has insulin receptors • in a number of regions (hypothalamus, hippocampus, cortex, basal ganglia) • In humans, intranasal spraying of insulin allows insulin to enter the brain without affecting plasma glucose levels – used in behavioural experiments • In hypothalamus, arcuate nucleus, paraventricular nucleus and both lateral and ventromedial hypothalamus have insulin receptors in abundance: • Insulin inhibits orexigenic neurotransmitters such as Agouti-related Protein and Neuropeptide Y • Insulin promotes cleavage of alpha-melanocyte-stimulating hormone  a-MSH which inhibits eating and stimulates energy expenditure

Answer 182

- 8-week treatment using intranasal insulin (4 sprays/day) compared to placebo resulted improvement of delayed memory in a word recall task (1 week after presenting words) (Benedict et al., 2004) - Intranasal insulin improved memory in elderly with Alzheimer’s dementia but not in healthy controls or people with mild cognitive impairment.

Answer 183

- Insulin resistance correlates with thinning of cortex, hippocampus and other brain regions. - A study involving 2,310,000 people and >100,000 with dementia revealed that Type II diabetes was associated with a 60% increase of risk of dementia of any origin.

Answer 184

``` Cortex: (all steroids) Glucocorticoids (cortisol, corticosterone) Aldosterone Androgens (dehydroepiandrosterone) Medulla: adrenalin, noradrenalin ```

Answer 185

``` Hormones that help to cope with stress (trauma, cold, infection, surgery, psychological stress) • increase glucose level (for muscles) • supports genesis of new glucose • mobilises free fatty acids (energy) • mobilises amino acids (new proteins?) • decreases immune responses • increases proteins in liver and plasma • (healing of injured tissues?) • decreases inflammation ```

Answer 186

Hypothalmic-pituitary-adrenal axis

Answer 187

Cortisol increased during TSST (trier social stress test) and peaked 30-45 min after onset of the stressor with no significant differences between males and females.

Answer 188

* Brain regions having receptors for cortisol are: hypothalamus, hippocampus, amygdala and prefrontal cortex * Slow, genomic effects of cortisol in the brain include synthesis of important neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, acetylcholine) * Fast, non-genomic effects refer to modulation of membrane-associated proteins and rapid changes in monoamine levels – not known too well. * Effects of cortisol on brain and behaviour are usually in form of an inverted

Answer 189

- Hypothalamic paraventricular nucleus secretes CRH which stimulates the release of ACTH in anterior pituitary, and ACTH stimulates secretion of cortisol in adrenal cortex. CRH also stimulates monoaminergic structures, locus ceruleus (noradrenaline) and nucleus accumbens (dopamine). - Cortisol exerts a negative feedback onto hypothalamus and pituitary. - Prefrontal cortex and hippocampus have inhibitory effect on the hypothalamic paraventricular nucleus. - Amygdala has a facilitatory (and possibly also inhibitory) effect on paraventricular nucleus (HPA).

Answer 190

* Increased subjective arousal, activity and mood (euphoria) * Self-reported level of attention is related to increases in cortisol concentration, * possibly via stimulating secretion of noradrenaline. * Cortisol improves encoding of threat-relevant memories. * Cortisol enhances responses to negative stimuli, e.g. acoustic startle reaction * Cortisol increases sensitivity to rewards and decreases sensitivity to losses * Decreased sensitivity to pain = stress-induced analgesia

Answer 191

- Plihal et al. (1996) administered cortisol, dexamethasone (a synthetic corticoid) or placebo to 10 participants over a 7 day period. - Plihal et al. (1996) administered cortisol, dexamethasone (a synthetic corticoid) or placebo to 10 participants over a 7 day period.

Answer 192

- administration of corticosterone into basolateral nucleus of amygdala in rats improves fear avoidance learning - Rats were trained to associate a tone with painful shocks. After 24 hours, a 10-s sound was presented (no shock) and reduction of motor activity (conditioned fear) was evaluated • Rats which received corticoterone injections into BLA facilitated the conditioned fear; this effect was abolished if rats were pre-treated with a beta-adrenergic blockade (atenolol).

Answer 193

Chronically elevated cortisol is associated with fatigue, anxiety, depression, apathy and impaired concentration • Prolonged periods of increased cortisol alters the structure of neurons in prefrontal cortex, amygdala and hippocampus. • Atrophic changes in hippocampus manifest in impaired verbal and declarative memory. • Note: amygdala, prefrontal cortex and hippocampus are three brain regions that modulate the activity of the hypothalamic paraventricular nucleus. • Chronically elevated cortisol initiates a cycle of imbalances within the HPA.

Answer 194

- Administration of corticosterone extends the size of dendrites in amygdala after 10 days.

Answer 195

* As shown in the left-hand panel, Knoops et al. (2010) took salivary cortisol samples six times during a day and analysed the volumes of hippocampus in hundreds of healthy males. Subjects were divided into thirds based on cortisol. Males with the largest evening values of cortisol levels had the smallest volumes of hippocampus after controlling for age, sex and physical proportions. * In the she study by Lupien et al. (1998), the volume of hippocampus was evaluated from MR images of brains of 51 older people. Plasma cortisol levels were evaluated once a year (24-hour data) for 5 consecutive years. Individual trajectories of cortisol levels were calculated: participants with a progressively increasing levels of cortisol were compared with participants showing a decrease or no change in their cortisol levels. High basal cortisol or a trend toward a long-term increase in cortisol levels correlated with decreased volume of hippocampus but also with decreases in a memory task.

Answer 196

``` • Stimulated by the sympathetic nerve system • AD and NAD survive in blood for only 2 min • Effects: • Increased heart rate and strength of o cardiac contractions • vasoconstriction in abdominal region • vasodilation in skeletal muscles • increased metabolism • glycogenolysis • increased CNS arousal ```

Answer 197

- The sympathetic-adrenal system receives nerve impulses from hypothalamus and therefore, adrenaline and noradrenaline play a major role in immediate emotional responses. - adrenaline will cause dilation of our pupils which changes our vision. For instance, drivers in whom pupillary dilation has been introduced by a sympathomimetic drug showed impaired contrast thresholds and a diminished visual acuity, basically a deterioration of vision. - Another interesting change is dilation of lung airways called bronchi. This effect serves in supporting a better exchange of gases in lungs and a better delivery of oxygen into the blood. - Muscles : blood flow increases to allow for contraction

Answer 198

- the systemic adrenaline binds to beta-adrenergic receptors on afferent terminals of the vagus nerve. Vagus nerve is the 10th head nerve and it is the main parasympathetic nerve innervating internal organs. - The vagus nerve projects onto the nucleus of solitary tract (NTS), a very large sensory nucleus on the ventral side of medulla. From NTS, there are direct projections to amygdala and indirect projections to amygdala via locus ceruleus (LC). - LC is the main source of noradrenaline in the brain. LC projects to the basolateral nucleus of amygdala and amygdala projects back to LC. - LC, along with other brain stem regions and hypothalamus, project to the spinal cord, to the mediodorsal part of the spinal cord from which sympathetic efferent nerves emanate.

Answer 199

- The brain regions will send excitatory impulses to the spinal cord either directly or indirectly via brainstem. Within the upper and middle part of the spinal cord, there is a large nucleus in which presynaptic sympathetic neurons originate. - The sympathetic fibres travel to the adrenal gland in the thoracic nerve and stimulate the release from its medulla of granules containing adrenaline and noradrenaline. The brain regions which send descending fibres to the spinal cord are hypothalamus and a number of brainstem nuclei, such as locus ceruleus, periaqueductal grey matter, raphe nuclei, and nuclei of the reticular formation.

Answer 200

- The left hand panel shows how systemic adrenaline stimulates the brain. We see molecules of adrenaline in the blood stream and in the tissues. Adrenaline binds to beta-adrenergic receptors on terminals of the vagus nerve. - Vagus nerve is a long nerve innervating many visceral organs. The nerve conveys the afferent impulses to a large sensitive nucleus in the brain stem called nucleus of solitary tract. - The solitary nucleus sends impulses to amygdala either directly, or indirectly via locus ceruleus. To recall, locus ceruleus is the main source of noradrenaline in the brain. Locus ceruleus sends noradrenergic fibres to the basolateral nucleus of amygdala, and amygdala in turn sends impulses to locus ceruleus. - The subregion in amygdala which sends to locus ceruleus is the central nucleus of amygdala. This arrangement explains how adrenaline and noradrenaline can cause or contribute to emotions because amygdala both contributes to sympathetic outflow and is modulated by adrenaline and noradrenaline.

Answer 201

- The firing of amygdala and locus ceruleus neurons is further modulated by cortisol. Cortisol changes the resting, phasic pattern of firing in locus ceruleus to a tonic pattern, and cortisol also strengthens the activity of amygdala. - Thus, now you can understand how both types of stress hormones, catecholamines and glucocorticoids cooperate to generate an adequate response to stress.

Answer 202

- A short stress or administration of cortisol will change brain activity and behaviour along two different networks. Brain’s salience network is a set of regions that sub-serve reorienting attention to novel or salient stimuli, detection of threats and triggering automatic actions that do not require elaborate thinking. - The brain regions which form the salience network are shown in the top right panel. The salience network encompasses anterior insula, anterior cingulate cortex, amygdala, thalamus, temporoparietal junction and inferior temporal cortex. - A large number of studies were compiled in the review paper by Hermans et al., to show that the salience network is strengthened during the first minutes following administration of exogenous cortisol or just after onset of a stressor, however, the strength of salience network decrease over time, and after about 60 minutes, the salience network drops off.

Answer 203

- In contrast, the executive network is suppressed initially and it takes over after about 90 minutes when the genomic effects of cortisol start to show off. The executive network comprises the dorsolateral and dorsomedial prefrontal cortex, frontal eye fields and dorsal posterior parietal cortex. - Executive network supports cognitive operations such as working memory, attentional span, reading span or cognitive flexibility. The scatter plot shows standardised performance in such tasks when performance was taken shortly after administration of cortisol or tens of minutes or hours later. - The take home message is, that non-genomic effects of cortisol and effects of adrenal hormones combine to increase sensitivity toward rapid and potentially threatening stimuli in the environment, however, these fast changes are later replaced by the genomic effects of cortisol which boost the more elaborate cognitive operations supported by the executive network.

Answer 204

- To illustrate how cortisol and noradrenaline interact in shaping emotional responses to distressing stimuli, the study by van Stegeren et al., took fMRI images during passive viewing of distressing pictures. The pictures ranged from neutral (labelled here as category 1) to the most distressing ones, category 4. Every participant was scanned twice, once after receiving a drug that blocked noradrenergic system and again after receiving placebo - . Participants were also divided into two groups, those showing a high cortisol increases during viewing emotional pictures and those showing low cortisol response. - Amygdala was much more active during viewing the most distressing category 4 and 3 pictures compared to neutral pictures if adrenergic system was operational, this would be the placebo condition. - The orange bars show that the group having high cortisol showed a much stronger amygdala activation than the group of participants with low cortisol response. However, these contrasts between high- and low cortisol responders were smeared if the noradrenergic system was shut down with propranolol. - Thus, amygdala will respond to distressing stimuli vigorously only if both cortisol level is high and noradrenergic transmission is operational. This study resembles the results of the study by Roozendaal et al., in rats shown in Part 4 in which the fear responses were strengthened in the presence of noradrenergic transmission and after cortisol was injected into basolateral nucleus of amygdala.

Answer 205

Endogenous fluctuations in hormone levels and looking at DM at periods of spontaneously low or high levels a hormone. • variation: correlating hormone level with DM after the task Administration of exogenous hormone vs. placebo and analysing DM behaviour before and after. • variation: precursor manipulation • variation: inhibiting a hormone Combined endo- and exogenous method: apply a hormone but measure also the baseline level of a hormone

Answer 206

Orbitofrontal, cingulate, ventromedial prefrontal, posterior parietal cortex, and ventral striatum (dopaminergic)

Answer 207

Ultimatum game : DM1 shares endowment with DM2 Dictator game : DM1 splits the endowment with no decision made by DM2 Trust game : DM1 sends, Experimenter trebles, DM2 splits

Answer 208

* Does OT penetrate the blood-brain barrier? It does, at high doses. * Intranasal spraying of OT does increase OT in cerebrospinal fluid * There are OT receptors in limbic system, basal ganglia and cortex * Hypothalamic neurons (SON, PVN) project to various DM regions

Answer 209

* hippocampus (CA1) * auditory cortex * piriform (olfactory cortex) * nucleus accumbens * cingulate cortex * ventral orbital cortex

Answer 210

- The neuronal and behavioural responses depend on the expression of OT receptors. - The expression depends on how strong the effect of OT will be. - The study shows the distribution of OT receptors in a mother mice, in virgins and in males. While all 3 mice have OT receptors in regions such as OFT or pyriform, the mothers mice have much stronger representation of OT receptors than virgins or males

Answer 211

- An isolated pup issues ultrasonic distress signals. A dam, a female parent, but not a virgin mouse will retrieve the pup. - After injecting OT or applying it to PVN (Opto), virgin mice also begin to retrieve the pups.

Answer 212

- Oxytocin concentration in DM2 greater after receiving a signal of trust compared to random assignments - Trustworthiness: What DM2 returns correlates with DM1’s offer (not in random condition): social reciprocity - Oxytocin level in DM2 correlated with the amount of money sent to DM1 in intentional condition but not in random condition

Answer 213

- Oxytocin or placebo sprayed into the nose of DM1 and DM tested 50 min later in a true trust game and in a risk condition (computer generates the amount of DM2’s returns). - The investor sends one of four levels of money and this is multiplied 3x. Then the trustee has his endowment of 12 plus the multiplied amount of transferred funds and decide how much he/she returns. The amount of transferred money is the trust signal. Trust (money transferred to trustee) was higher in OT group of investors compared to Placebo group.

Answer 214

OT increased the amount of funds sent in UG.

Answer 215

Number of donations did not increase with OT, only the amount of donations in those who decided to donate.

Answer 216

- Oxytocin level 1 month after the birth correlated with maternal behaviour manifested in the duration of gaze, affective attitude and touching the child.

Answer 217

- OT enhances stimulating parental behaviour in fathers

Answer 218

* No differences in OT levels in week 1 and month 6 between fathers and mothers * Increase in OT levels from week 1 to month 6 in both * Strong correlations between father’s and mother’s OT levels * OT is associated with affectionate parenting in mothers and with stimulating parental behaviour in fathers

Answer 219

- Viewing infant faces activates hypothalamic OT region and the reward system - OT increases during playing with own baby in secure mothers - Secure mothers (A) but not insecure mothers (B) continue activating their reward system if infant’s face is sad.

Answer 220

- This study documents effects of OT in increasing saliency of others. Cues showing first names of either self or -somebody else were shown, followed by a picture depicting a potentially painful scenario or a graphically matching non-pain scenario. - Thus, pictures were presented in self-perspective or other-person perspective. Oxytocin or placebo were sprayed into nostrils before the experiment. - Results show that only in OT condition but not in placebo condition, pain ratings were larger if pain pictures were preceded by someone else’s name, not own name. This data is consistent

Answer 221

- the cellular layers are backwards. Light has to travel through multiple layers in order to get to the rods and cones that act as the photo-receptors. There is no functional reason for this arrangement – it is purely quirky and contingent. - Even in a healthy and normally functioning eye this arrangement causes problems. Because the nerve fibers coming from the rods and cones need to come together as the optic nerve, which then has to travel back to the brain, there needs to be a hole in the retina through which the optic nerve can travel. This hole creates a blind spot in each eye. Our brains compensate for this blind spot so that we normally don’t perceive it – but it’s there.

Answer 222

Went to South America at the age of 22. Made some observations such as: • Marine iguanas are different from land iguanas • Mockingbirds looked a little bit different in different islands • Tortoises that ate plants near the ground had rounded shells and shorter necks. Tortoises on islands with tall shrubs had longer necks and shells that bent upward, allowing them to stretch their necks • He gave his collection of finches to British Museum and they noticed that they varied.

Answer 223

- The environment cannot support an unlimited population growth. - Organisms are in constant competition not just for food but other resources too. - Organisms vary in traits..

Answer 224

Environmental factors that increase or decrease the likelihood that a particular combination of genes makes it to the next generation. Advantageous traits are selected disadvantageous traits are not.

Answer 225

Fast evolution: resistance to antibiotics: 6 months. It happens when populations are large and selection pressure is strong Big populations have lots of genetic variation Selective breeding: every time you try to change one trait you have a byproduct, you have an implicit selection going on, on other traits. So although you may be realising a benefit in one, or a place, you are paying a cost in the others.

Answer 226

* Principle of natural design for gene replication * Superabundance * Natural variance * Selection pressures

Answer 227

we are a constellation of genes that drive physiological processes and behaviours. Evolution does not operate in individuals, rather evolution operates in genes. Genes need to make it to the next generation

Answer 228

animals and plants produce more offspring than necessary.

Answer 229

In evolution, organisms cannot invest in everything, so they either invest in one trait or another This is called an evolutionary trade off. A trade-off is a situation where to gain some advantage, you have to pay a price. For instance big brains are certainly nice to have but they are costly in terms of the energy they use up, make childbirth difficult, and are easily damaged.

Answer 230

- Intersexual competition: attributes that females and males use to select mates. - Men look for indicators of fertility - Females look for good genes and resources.

Answer 231

Social or group selection pressure: organism who are better able to get along with the group have greater chances to reproduce. Cooperative wolves morel likely to reproduce.

Answer 232

- Ability to infer others' emotions - Discern kin from non-kin - Identify and prefer healthier mates - Cooperate with others

Answer 233

- This hypothesis argues that the evolution of the scrotum was driven by increases in physiological body temperature (endothermic pulses) that occurred in Boreoeutheria (a clade of mammals, supported by genomic data, that comprises the rodents, primates, lagomorphs such as hares and rabbits, carnivores, bats, and ungulates) during the Cenozoic - . These pulses occurred as an adaptation to climate changes, and as an adaptation to cursoriality (the ability to run, which increases body temperature). The model proposes that selection maintained an optimum temperature for spermatogenesis and sperm storage throughout the Cenozoic, at the lower levels of body temperature that prevailed in ancestral mammals for at least 163 million years. - The lower temperatures also favor a reduced rate of mutation during spermatogenesis, and evolutionary processes ended up stabilizing these lower temperatures for sperm production and storage. Evolutionary stasis may have been driven by reduced rates of germ-cell mutations at lower body temperatures. - The fitness advantages of an optimum temperature of spermatogenesis ultimately outweighed the costs of testes externalization and resulted in the evolution of the scrotum. This hypothesis would explain why elephants do not have external testes (they are not Boreoeutheria, but belong to another clade, Afrotheria, comprising tenrecs, hyraxes, and elephants.

Answer 234

- There can be non-adaptive evolutionary by products: spandrels - A belly button is not good for catching food, detecting predators, avoiding snakes, locating good habitats, or choosing mates. It does not seem to be involved directly or indirectly in the solution to an adaptive problem. - By-products (spandrels) of large brains could be: religion, reading, writing, fine arts, the norms of commerce, and the practices of war.

Answer 235

- Some vestigial features are structures: They are often homologous to structures that are functioning normally in other species. - Other vestigial features can be behaviours or reflexes - Vestigial features can be considered evidence for evolution - There are more that 100 vestigial features in humans:

Answer 236

- NOT all existing behaviours or structures evolved to perform its current function - These are called EXAPTATIONS: evolved to serve one function and were later used for another - Dinosaurs evolved feathers for keeping warm. They later evolved to do more than their original purpose.

Answer 237

- Similarities among species do not necessarily mean that the species have common evolutionary origins - Structures that are similar because they have a common origin are termed homologous Structures that are similar but DO NOT they have a common origin are termed analogous - The similarities between analogous structures result form convergent evolution: Evolution in unrelated species of similar solutions to the same environmental demands

Answer 238

``` Agile hands: tools Colour vision: opportunities and dangers Mastery of fire Bipedalism: Walk long distances Carry tools and food Linguistic abilities: pass information make plans form complex civilisations - All products of a large brain ```

Answer 239

* Elephant brains can be bigger, but ours is better. * It has a much larger cerebral cortex than we should have for the size of our bodies. * So that would give us extra cortex to do more interesting things than just operating the body. * The main reason for saying that our brain is larger than it should be actually comes from comparing ourselves to great apes. * Gorillas can be two to three times larger than we are, so their brains should also be larger than ours, but instead it is the other way around. * Our brain is three times larger than a gorilla brain. * The human brain also seems special in the amount of energy that it uses. Although it weighs only two percent of the body, it alone uses 25 percent of all the energy that your body requires to run per day. That's 500 calories out of a total of 2,000 calories, just to keep your brain working

Answer 240

* In larger rodent brains, the average size of the neuron increases, so the brain inflates very rapidly and gains size much faster than it gains neurons. * Primate brains gain neurons without the average neuron becoming any larger, which is a very economical way to add neurons to your brain. * The result is that a primate brain will always have more neurons than a rodent brain of the same size, and the larger the brain, the larger this difference will be. * Humans have, on average, 86 billion neurons, 16 billion of which are in the cerebral cortex, * If a human brain was made like a rodent brain. It would weigh 36 kilos. * That's not possible. A brain that huge would be crushed by its own weight, and this impossible brain would go in a body of 1.8 tons

Answer 241

- A generic primate with 86 billion neurons would have a brain of about 1.2 kilos, in a body of some 66 kilos. So the human is not special in its number of neurons. It is just a large primate brain - All brains use the same energy: an average of six kcal per billion neurons per day (6 x 86=516kcal) - The reason why the human brain costs so much energy is because it has a huge number of neurons. - We are primates with many more neurons for a given body size than any other animal, the relative cost of our brain is large, but just because we're primates, not because we're special.

Answer 242

a trade-off between body size and number of neurons. - A primate that eats eight hours (900 kcal) per day can afford at most 53 billion neurons, but then its body cannot be any bigger than 25 kilos. - To weigh any more than that, it has to give up neurons. So it's either a large body or a large number of neurones. - If you eat like a primate, you cannot afford both, orangutans, for instance, afford about 30 billion neurons by spending eight and a half hours per day eating. What about us? With our 86 billion neurons and 60 to 70 kilos of body mass, we should have to spend over nine hours per day every single day feeding, which is just not feasible. If we ate like a primate, we could not be here

Answer 243

* Genes that slow down the process of brain development allowing more time for growth * At birth brain weights 350 g and contains 100 billion neurones * After birth it continues to grow HOWEVER.. Production of the majority of neurones stops * Neurones grow and establish connections with each other * Glia proliferate * Genes that control the size and complexity of the brain have undergone much more rapid evolution in humans than in non-human primates or other mammals

Answer 244

* Mammals, and especially humans are born with a larger brain which has an abundance of neural circuits that can be modified by experience. * Adults provide their young with skills they will need as adults. * Some specialised circuits are necessary (such as analysing the complex sounds that we use for speech) but overall the brain is a general purpose programmable computer

Answer 245

is the most prevalent in mammals One male forms mating bonds with more than one female. It evolved because males investment in offspring compared to females is minimal. Father can sire many many offspring

Answer 246

one female forms mating bonds with more than one male. It does not tend to happen in mammals. It happens in species where the male investment is bigger than the female’s.

Answer 247

* Monogamy is thought to have evolved in mammalian species in which each female could raise more young if she had undivided help. * In such species, any change in the behaviour of a female that would encourage a male to bond exclusively with her would increase the likelihood that her genes would be passed to future generations. * One behavioural change is to drive other females of reproductive age away from her mate.

Answer 248

stress will be defined as the cognitive perception of uncontrollability and/or unpredictability that is expressed in a physiological and/or behavioural response (Koolhaas et al., 2011). A stressor is an unpredictable and/or uncontrollable stimulus.

Answer 249

Epidemiological transition - theory which describes changing population patterns in terms of fertility, life expectancy, mortality, and leading causes of death. Worldwide shift from infectious to non-infectious disease.

Answer 250

Social gradient: people who are less advantaged in terms of socioeconomic position have worse health (and shorter lives) than those who are more advantaged.

Answer 251

 A > B > C etc (constant threat to subordinates).  Stressful dominance behaviour - physical & psychosocial: (C) Male savanna baboons may fight over a kill (D) Dominant male baboon intimidates a subordinate

Answer 252

``` According to Sapolsky - socioeconomic status is the nearest human approximation to social rank. A classic example of research on this subject is the Whitehall study of British civil servants. Data revealed a steep inverse association [social gradient] between social class and health and mortality from a wide range of diseases. ```

Answer 253

• Worse health outcomes for those at the bottom – more social issues (e.g., crime). • Less social mobility [social reproduction] • Less social cohesion • More conspicuous consumption • More status anxiety [social evaluative threat] ■ Bigger the income divide – greater the differences in lifestyle [way of life] and health. Lack of control/predictability and participation.

Answer 254

Disproportionate share of physical and psychosocial stressors. - Whitehall studies. Michael Marmot. - The Black report concluded that smoking, diet, and other behavioural factors with biological effects contribute to, but do not fully explain, health inequalities.

Answer 255

Control : Worry about not being able to get by. Home [warm shelter], food, safety, work [true necessities – survival; absolute need]. Participation – “capabilities : Absolute poverty vs relative poverty. Relative poverty is a social construct. Living in poverty UK – different from Africa Social comparisons and evaluative threat : Relative needs and going without. Social inclusion. Linen shirt [customary] – Adam Smith 1776. Stealing to maintain dignity. 21st century – car ownership, holiday etc. What it feels like to be poor and unable to engage in all that society has to offer. • Judgement, shame, stigma, dignity. These factors are society specific.

Answer 256

* Negative social effects of wide inequality. * More physical and mental illness among those at the lower ranks [& social gradient]. * Heightened levels of social distrust, social evaluation. * Consequences of rank dependent on society. Small differences in material resources – hunter gatherer. * 1950/60s - CEO 25/30 X the wages of worker. * 2005 - WalMart CEO – 900 X the wages of worker. * Worries about self worth and presentation - self doubt, social/status anxiety, stress.

Answer 257

The Hassles and Uplifts Scales (HSUP) measures respondents attitudes about daily situations defined as "hassles" and "uplifts." Instead of focusing on highly charged life events, the HSUP provides a comfortable way to evaluate positive and negative events that occur in each person's daily life. The HSUP has three forms: • Daily Hassles Scale (DHS) • Daily Uplifts Scale (DUS) • Combined Scale (HSUP): Includes items selected from DHS and DUS. "HSUP" refers to this form and the instrument as a whole.

Answer 258

Activate a physiological system [for months] that has evolved for responding to acute physical emergencies

Answer 259

■ Staying in balance. ■ Maintaining optimum conditions for function [enzyme and cell], in response to internal and external changes. ■ Body temperature, blood glucose concentration, water levels. ■ Stress-response – body’s response to re-establish homeostasis ■ Humans to expand the concept - Stressor can be the anticipation of event happening.

Answer 260

- Hans Selye extended the work of Cannon. - Selye was a medical researcher who studied hormonal changes in rats. In his experiments, rats that received hormone injections and those that received placebos, developed ulcers. - Selye discovered that rats were undergoing "stress”. It was the stressful environment [lack of control, lack of predictability] that caused the rats to become ill and die. - Selye theorized that overexposing the body to stress would cause what he called “general adaptation syndrome”.

Answer 261

Often considered the first theory of stress, the GAS states that there are three stages to the stress response: 1. Alarm where the individual mobilises resources to cope with exposure to a stressor. 2. Resistance where the individual copes with the impact of the stressor. 3. Exhaustion where the individual has depleted their resources coping with the impact of the stressor (this does not imply that the impact of the stress has actually been successfully dealt with).

Answer 262

- hypothalamus, pituitary gland, adrenal gland

Answer 263

- Produce many components of stress

Answer 264

sympathetic-adrenal-medullary (SAM) system | Release of Epinephrine and norepinephrine

Answer 265

• Distress signal to the hypothalamus (command centre). • Sympathetic nervous system - triggers the fight-or-flight response. • Adrenal glands pump epinephrine & norepinephrine into bloodstream. • Heart beats faster, pushing blood to the muscles, heart, other vital organs. • Epinephrine - release of blood sugar (glucose) and fats – these supply working muscle • Phase 2 starts - HPA axis [hypothalamus, pituitary gland, adrenal glands. 7. Parasympathetic nervous system — the "brake

Answer 266

``` Adrenal medulla (Adrenaline and noradrenaline) Adrenaline (The “fight-or-flight hormone”) Acute stress response Short-term capacity Affects cardiovascular system Mobilises the body for action ```

Answer 267

``` Adrenal cortex (Cortisol) Cortisol (The “stress hormone”) Chronic stress response Long-term capacity Affects immune system Keeps the body in state of alert ```

Answer 268

Cannot fully understand stress by examining environmental events (stimuli) and people’s behaviour (responses) as separate entities. They are a transaction – in which people adjust to daily stressors. Coping strategies. • People appraise situations differently • Cognitive appraisals are susceptible to mood, motivation and motivational state – traffic light example; more an issue when in a rush. • Body’s stress response similar when experienced and/or merely imaged.

Answer 269

• Potential stressor - Sound of a car horn 2. Primary appraisal – Am I in danger? Why are they honking at me? Irrelevant – They’re honking at someone else/ Benign-positive – It’s me mate, saying hiya. Challenging – They’re warning me my car is drifting. • Secondary appraisal – What can I do? Am I going to be able to avoid accident? • Behavioural and cognitive coping responses – (Adjust steering to re-centre car). 5. Reappraisal – How am I doing? Is it under control?

Answer 270

- Locus of control is an individual’s belief system regarding the causes of his or her experiences and the factors to which that person attributes success or failure. - People with an external locus of control are more likely to experience anxiety since they believe that they are not in control of their lives.

Answer 271

- Attribution theory argues that individuals are motivated to understand the causation of events as if the world were predictable and controllable. - The locus of control is a binary condition, it is either internal (e.g. it is all my fault) or external (e.g. it is someone else’s fault).

Answer 272

The type A personality generally lives at a higher stress level. This is driven by: * They enjoy the achievement of goals, with greater enjoyment in achieving of more difficult goals. * They are thus constantly working hard to achieve these. * They find it difficult to stop, even when they have achieved goals. * They are highly competitive. They hate failure and work hard to avoid it. * They are often pretty fit and well educated (result of anxiety). Describe the type B personality The type B personality generally lives at a lower stress level. This is driven by: • They work steadily, enjoying achievements but not becoming stressed when unachieved. • When faced with competition, don’t mind defeat, enjoy the game or back down. • They may be creative and enjoy exploring ideas. • They are often reflective.

Answer 273

``` ■ Control ■ Predictability ■ Outlets for frustration ■ Social support ■ A perception of things worsening ```

Answer 274

Dr. Jay Weiss of Rockefeller University. Two rats are connected to a stressor — an electric shock to the tail. One rat is able to turn off the stimulus by turning a wheel, while the other receives the stress stimulus regardless of what it does. The rat with more control is shown to suffer fewer deleterious health consequences.

Answer 275

 London bombed each night  Suburban areas more sporadic bombing [less predictability]  More ulcers

Answer 276

- Rats given a wooden block will gnaw on it as an outlet | - Rats without took aggression out on a fellow rat

Answer 277

Family research: Higher glucocorticoid levels among stepchildren vs biological children

Answer 278

External Sex In humans sex is usually defined both medical and in lay terms by the outward appearance of the individual from birth (external genitalia). Internal Sex The internal reproductive organs. Chromosomal Sex Genetic male (XY) or genetic female (XX).

Answer 279

Other behaviours that are regarded as ‘female-typical’ and ‘male-typical’ (e.g. parental behaviour, aggressiveness, emotional intelligence, visuospatial skills and so on…).

Answer 280

Genetic females possess two X chromosomes (XX) | Genetic males possess an X and a Y chromosome (XY)

Answer 281

Humans have 23 pairs of chromosomes (46 total) in almost all cells 22 pairs of autosomes and 1 pair of sex chromosomes

Answer 282

These cells only have half the chromosomal complement: 22 autosomes and 1 sex chromosome

Answer 283

Sex is decided by the sperm Females are homogametic Males are heterogametic

Answer 284

The system is reversed in butterflies and moths - the female is heterogametic

Answer 285

At six weeks after conception, all embryos (whether XX or XY) are still physically identical. They ALL possess: Internal embryonic glands termed primordial gonads. Cortex could become ovary, medulla could become testes. Müllerian ducts which have the potential to develop into female internal organs. Wolffian ducts which have the potential to develop into male sexual organs No external primary sexual characteristics.

Answer 286

``` Wolffian ducts (have the potential to develop into male sexual organs) Müllerian ducts (have the potential to develop into female internal organs) ```

Answer 287

- In the 7th week in males (XY) embryos, the Sry gene on the Y chromosome triggers the synthesis of Sry protein Sry protein stimulates the medulla of the primordial gonad to develop into a testis. In 3rd month of development, the embryonic testes produce two hormones: The androgen testosterone AMH (anti Mullerian hormone/Mullerian inhibiting substance)

Answer 288

causes the male embryo to develop male internal and external genitalia (seminal vesicles, scrotum, penis etc.) from Wolffian system, other internal tissue, and germinal ridge. Masculinising Effect

Answer 289

prevents the development of female internal genitalia from Müllerian system (these wither) & causes testes to descend into scrotum. Defeminising Effect

Answer 290

Females are XX and without the Y chromosome they have no SRY gene and therefore no Sry protein is produced. - Differentiation of internal ducts of female reproductive system is not under hormonal control. Just ABSENCE of testosterone. - The normal development of internal female genitalia from the Müllerian ducts and other tissue (uterus, fallopian tubes, etc.)

Answer 291

``` End of 2nd month of pregnancy, external differences start to appear as 4 structures of bipotential precursor begin to develop. Glans: Head of penis Clitoris Urethral fold Fuse Become labia minora Lateral body Shaft of penis Hood of clitoris Labioscrotal swelling Scrotum Labia majora ```

Answer 292

The transitional period between childhood (low levels of circulating gonadal hormones, immature reproductive organs, males and females physically similar) and adulthood. Key components: Growth spurt. Development of secondary sexual characteristics. Fertility is achieved.

Answer 293

Stage 1 is prepubescent and stage 5 is adult Girls defined by breast and nipple area (areola and papilla) development In girls breast development usually starts in stage 2 (8-14 yr) In girls first menstruation occurs around stage 3 (9-15 yr). Ovulation generally occurs in stage 4 (10-16 yr).

Answer 294

Boys defined by development penis and testes. Stage 2 - Scrotum and testes enlarge (9-15 yr). Stage 3 – growth of penis in length (11-16 yr). Stage 4 - penis is further enlarged in length and breadth, development of glans, testes and the scrotum are further enlarged (11-17 yr).

Answer 295

Poorly understood but likely to be numerous internal and external cues “biological clock” Explanation supported by rising age of onset in developed nations in line with improved diets, medical care, socioeconomic conditions (Eckert-Lind et al., 2020)

Answer 296

GnRH = gonadotropin-releasing hormone LH = luteinising hormone FSH = follicle stimulating hormone LH and FSH are known as “gonadotropic hormones” or “gonadotropins” This controls development of primary sexual characteristics (external) and internal systems

Answer 297

``` Gonadotropic hormones (FSH & LH) Testes: start to produce sperm (spermatogenesis) and rapid increase in testosterone release Some testosterone converted into dihydrotestosterone, which triggers growth and development of penis ```

Answer 298

Gonadotropic hormones (FSH & LH) Ovaries: Stimulated to release the hormone estradiol (an estrogen) Maturation of female genitalia and Release of first ova and first menstrual cycle begins Estrogen and progesterone (controlled by FSH & LH) co-ordinate the menstrual cycle

Answer 299

In pubertal males: androgen levels > estrogen levels

Answer 300

In pubertal females: estrogen levels > androgen levels

Answer 301

FEMALES These include the development of breasts, change in figure due to adipose tissue increasing around the bottom and thighs. The development of underarm and pubic hair in females (controlled by androstenedione, an androgen). MALES These include the broadening out of figure, the deepening of the voice, and the development of facial, underarm and pubic hair.

Answer 302

Rising levels of androgens change fatty acid composition of perspiration, resulting in a more "adult" body odour. Another androgen effect is increased secretion of oil (sebum) from the skin increasing susceptibility to acne vulgaris.

Answer 303

Hormonal peaks mark obvious changes in the behaviour of both males and females. Most adolescents develop an interest in sex. In males in particular, peaks in testosterone levels appear to correlate with a marked surge in sex drive. Testosterone peaks may also be responsible for a variety of other behavioural changes and experiences such as: rapid mood swings, reduced attention span, aggression

Answer 304

Requires remodelling and activation of neural circuits involved in salience of sexual stimuli and sensory associations, sexual motivation and sexual performance.

Answer 305

Physical differences Size Typical number of nuclei and fibre tracts Numbers and types of neural and glial cells Numbers and types of synapses

Answer 306

Gonadal and adrenal sex hormones are steroids (derived from cholesterol). They have similar structures and so can be readily converted from one to the other.

Answer 307

It is thought that the brain (specifically the hypothalamus) is masculinized by perinatal (around the time of birth) estradiol that has been aromatized from testosterone, rather than testosterone itself. Evidence (animal studies): Early injections of estradiol masculinizes rodent brains. If testosterone is administered along with agents to block aromatization, masculinization of the rodent brain does not occur. If androgens that cannot be aromatized are administered (e.g. dihydrotestosterone), masculinization of the rodent brain does not occur.

Answer 308

Alpha fetoprotein binds to and deactivates circulating estradiol

Answer 309

Testosterone is immune to it! Testosterone travels to the brain and is converted to estradiol. Alpha fetoprotein can’t get past the blood brain barrier.

Answer 310

Experiments of neural control of sexual behaviour not ethical in humans Information obtained from: Laboratory animals. Humans with developmental disorders. Sex hormones are critical Again, default program is to develop a female

Answer 311

Prenatal Development of nervous system Specific areas of brain driving male and female specific sexual behaviours

Answer 312

Puberty/adulthood Activation of nervous system Hormones interact with specific areas to drive sexual behaviours

Answer 313

Behavioural masculinisation Androgen-stimulated development of the brain areas that will respond to testosterone in adulthood and produce male sexual behaviour Behavioural defeminisation The inhibitory effects of androgens on the development female brain areas that would respond to estradiol and progesterone in adulthood to stop the production of female sexual behaviour

Answer 314

An attractive 26 year old female Married and trying to have a baby with partner for 4 years Believed that lack of a menstrual cycle might be the problem Symptoms No external abnormalities But uterus underdeveloped Internal exam revealed testes Hormone levels those of a male Chromosomally a male (XY) Believed cause: Androgenic insensitivity syndrome Normal male androgen levels, but no response to them She does respond to estrogens, so she effectively has more estrogens than androgens – leading to the development of female secondary sex characteristics Suggests that androgens responsible for male sexual development

Answer 315

Genetic female Born with somewhat ambiguous genitals so parents raised her as a girl Developed male secondary sex characteristics in puberty Extremely distressing Diagnosed with Adrenogenital syndrome Congenital defect in the release of cortisol Leads to excessive release of adrenal androgens This results in secondary masculine features (e.g. deep voice, facial hair) Given physical and hormonal surgery to make her more feminine 15 years later was married and had a normal sex life

Answer 316

Surgeon's error led one of a pair of male twins having penis destroyed Leading developmental Psychologist (Prof John Money) suggested should be raised female Seen as a direct test of nature v nurture (genetically identical twin as the control) Artificial vagina created Estrogen administered at puberty At age 12, Money (1975) reported that Joan had developed into a female Seen as evidence for the role of culture over the masculinising effects of male genes and androgens But….a long-term follow-up study (Diamond & Sigmundson, 1997) tells different story John/Joan never felt or acted like a girl Preferred male toys Tried to urinate standing up Masculine mannerisms led to bullying and expulsion from school for aggressive retaliation John/Joan chose to become John later in life, but never recovered from the ordeal David Reimer ‘Joan/John’ remained bitter about his treatment and helped write his biography: David (“John”) took his life in May, 2004

Answer 317

Break down food to amino acids and simple sugars, which then pass into the bloodstream → liver.

Answer 318

Glycogen is stored in the liver and muscles and is readily converted to glucose – the body’s main usable source of energy.

Answer 319

Preparation to eat

Answer 320

Energy from the meal is absorbed into bloodstream to meet body’s immediate energy needs (excess energy is stored).

Answer 321

Unstored energy from the meal has been used. Energy is withdrawn from stores to meet body’s immediate needs.

Answer 322

Insulin - released by the pancreas during cephalic and absorptive phases. Three main functions: Promotes glucose use as the body’s primary energy source. Promotes conversion of bloodborne energy to glycogen, fat and proteins. Promotes energy storage in liver, adipose (fat) tissue, and muscles.

Answer 323

- released by the pancreas during the fasting phase. Main function is to trigger conversion of stored energy to usable fuel by: Promoting release of free fatty acids from adipose tissue and their use as body’s primary fuel. Stimulating conversion of free fatty acids to ketones (used as energy source by muscles). Explain what happens to insulin levels during the fasting phase Insulin levels are low during the fasting phase → Glucose stops being the body’s primary fuel and is saved for the brain. Low levels of insulin promote conversion of glycogen and protein to glucose.

Answer 324

``` Energy balance (EB) Homeostasis = a stable environment. Energy intake (EI) minus energy expenditure (EE). In an ideal homeostatic energy system an organisms energy intake should equal energy expenditure. Homeostatic eating = eating behaviour that functions to produce an equilibrium (energy balance - EB). (EB = EI - EE) ```

Answer 325

Feedback from changes in one direction elicit compensatory changes in the opposite direction. Negative feedback system act to maintain homeostasis.

Answer 326

Set point = the body’s energy resources are maintained at optimal level. After eating, energy resources are close to the set point. Energy resources decline as the body uses energy to fuel physiological processes. Energy resources fall far enough below the set point → hunger and eating. Eating continues until energy level returns to set point → satiety.

Answer 327

Mayer (1955)Glucostatic theory: Eating is regulated by a system designed to maintain a blood glucose “set-point”. ↓ in blood glucose significantly below set-point – HUNGER ↑ in blood glucose as a result of eating and return to set-point – SATIETY Lipostatic theory: There is a set-point for body fat. Deviations from this set-point produce compensatory adjustments in eating that return levels of body fat to set-point. Glucostatic theory - short-term regulation (i.e. meal initiation and termination) Lipostatic theory - long-term regulation. Dominant perspective in the 1950s, but now known to be overly simplistic

Answer 328

Humans and animals are not normally driven to eat by internal energy deficits. Instead, the anticipated pleasure or incentive (reward) value of eating is critical. Environmental cues associated with food reward can trigger the desire to eat. Food’s incentive value is shaped by emotional, cognitive and environmental factors.

Answer 329

The decline in the pleasantness of a food as it is eaten relative to an uneaten food. An adaptive mechanism. Makes it easy for us to over-eat when there is a lot of variety.

Answer 330

Consumption of a palatable food produces a small increase in hunger early in the meal, relative to a bland food and a food with overly strong flavour.

Answer 331

Human food consumption which is driven by pleasure, not by the need for calories. People experience thoughts, feelings and urges to consume food in the absence of energy deficit (homeostatic hunger) Exacerbated in modern food environments. Areas of the brain which mediate hedonic eating are distinct from areas which mediate homeostatic eating. Restrained eating/dieting involves eating less than wanted.

Answer 332

Systematic review of evidence on the influence of the food environment on child obesity. Strongest impact was found for (1) availability of sugar-sweetened beverages, (2) large portion sizes, and (3) food promotion and advertising. Reduction to these three elements likely to hold promise in obesity prevention among children.

Answer 333

Mice who were homozygous for the ob gene (ob/ob) were dramatically obese. Ob/ob mice ate more than control mice. Also converted calories to fat more efficiently. Blood from thin mice reduced body weight of obese mice. Ob/ob mice did not have a key blood factor called leptin because they were born without required gene code.

Answer 334

Leptin is a negative feedback signal that controls levels of body fat (adipose tissue). Leptin is released from the adipose tissue when they are plentiful Stimulates leptin receptors in the arcuate nucleus (ARC) of the hypothalamus Satiety signals are released (e.g. α-MSH) → Decreased food intake Increased metabolism of fat stores also occurs 4. Levels of adipose tissue are reduced.

Answer 335

Rare condition in humans where, due to a single gene defect, leptin cannot be produced. Children demonstrate excessive weight gain and appetite. Administration of recombinant leptin completely reverses this condition BUT, most obese people do not possess a leptin deficiency. In fact, they produce excess leptin. It has been suggested that they display leptin insensitivity or leptin resistance.

Answer 336

Body weight is highly heritable. Twin and family studies indicate 47–90% heritability. Many common genetic variants [single nucleotide polymorphisms (SNPs)] have been identified, which collectively explain ∼3% of the variation in BMI. Genetic risk of obesity is thought to operates via the neurobiology controlling appetite regulation: Manifests as the tendency to overeat when prompted by environmental food cues and the opportunity to eat.

Answer 337

Adults who were homozygous for the risk allele (AA) weighed about 3 kg more and had increased odds of obesity compared to those not inheriting a risk allele (TT). Compared to participants without high-risk allele (i.e. TT), participants with FTO high-risk allele (i.e. AA): Had higher levels of ghrelin, the “hunger hormone”. Felt more hungry after eating. Had differential brain responses to pictures of food (in hypothalamus and reward-related regions). Consumed more fat and total energy (even when controlling for higher BMI). → FTO exerts effects on weight via directly influencing neurobiology of appetite control.

Answer 338

During most of human evolution, food was often scarce and came at a high cost of physical activity. The capacity to consume large meals and easily store energy as fat would have ensured survival. “Thrifty gene” hypothesis (Neel, 1962): Genes that promote storage of energy as fat during periods when food was abundant. During famines, individuals with the ‘‘thrifty’’ genotype would have a survival advantage. But these same genes are counter-productive in modern “feast” environments.

Answer 339

A learned response. Exposure to food cues elicits conditioned responses such craving, attentional bias, physiological changes, and brain activation. People who are addicted to drugs (nicotine, heroin, cocaine) also show these responses to drug-relevant cues.

Answer 340

Both food cues and smoking cues activated (i) the left amydala, and (ii) the striatum – specifically the nucleus accumbens (part of the ventral striatum). These brain areas are important for learning, memory and motivation.

Answer 341

Dopamine is released in response to drug and food cues. People who abuse drugs and people with severe obesity have very similar abnormalities in dopamine D2 receptors in the striatum Lower availability of these receptors in the striatum (key brain reward region).

Answer 342

DSM-5 criteria for Substance Use Disorder: Hazardous use Social or interpersonal problems related to use Neglected major roles to use Withdrawal Tolerance Used larger amounts and/or for longer amounts of time Repeated attempts to control use or quit Much time spent using Physical or psychological problems related to use Activities given up to use Craving Yale Food Addiction Scale (YFAS) Enables a diagnosis of food addiction based on the DSM-5 criteria for substance dependence:

Answer 343

Schulte et al. (2015) PLoS One. 2015; 10(2): e0117959. Pizza, chips, cheeseburgers, chocolate, cake, cookies, bacon and ice cream are the foods most often associated with addiction. Foods least associated with addiction were brown rice, apple, beans, carrots and cucumber. → Highly processed foods (high in fat and/or refined carbohydrate) are particularly associated with food addiction.

Answer 344

(eg. Goldstein & Volkow 2002; Jentsch & Taylor 1999; Wiers et al., 2007; Deutsch & Strack 2006) Impairments in inhibitory control are associated with: Alcohol abuse (e.g. Christiansen et al., 2012) Cocaine use (e.g. Colzato et al., 2007) Amphetamine use (e.g. Hammerslag 2014) Opiate dependence (e.g. Liao et al., 2014) We should not focus on cue reactivity to the detriment of other processes that we know are implicated in addiction.

Answer 345

If sugar was addictive, we would be eating bags of the stuff! Markus et al. (2017) - majority of participants experienced problems controlling intake of high-fat savoury and high-fat sweet foods. Only a minority experienced problems for mainly sugar-containing foods. Energy density of foods appears to be the critical factor, probably because consumption of calories is essential for our survival. Markus et al. (2017). Appetite, 114, 64-72. Everyone listening probably gets exposed to high fat foods daily but is not an addict. If everyone was exposed to nicotine, cocaine or heroin as often you’d all be addicts!

Answer 346

Participants commonly report effects such as increased cravings and low mood when abstaining from problematic foods. BUT this is not the same as withdrawal from drugs e.g. heroin withdrawal associated with sweating, irritability, dilated pupils, leg cramps, muscle twitches, low grade fever, increased blood pressure, stomach cramps, nausea, vomiting, diarrhoea, rapid breathing, and weakness. Alcohol withdrawal, fever, high blood pressure, confusion, hallucinations, trembling and even seizures

Answer 347

Often described as a chronically relapsing disorder characterized by Compulsion to seek and take substance Loss of control limiting intake Emergence of a negative state when access to substance is prevented (e.g. physical and/or psychological withdrawal)

Answer 348

The study of how genetics and environment contribute to disease 40-60% of vulnerability to addiction has been attributed to genetic factors This includes the percentage of variance attributed to 1) genetic factors alone and 2) gene-environment interactions

Answer 349

AUD/SUDs are one of the largest contributors to the global burden of mortality and premature death. Also a high economic burden Most importantly – they are preventable (non-communicable disease) Disability Adjusted Life Years (DALYs): The sum of years of potential life lost due to premature mortality and the years of productive life lost due to disability

Answer 350

In the UK: rates of smoking are declining (taxation and the smoking ban have helped) the number of people who drink alcohol has declined, but among drinkers the number of people who drink too much has increased (pricing and availability probably played a role again) New drugs become fashionable (e.g. mephedrone), others fall out of favour (e.g. ecstasy) E-cigarettes seemed to come out of nowhere and have divided opinion

Answer 351

Key claims: All drugs of abuse effect (directly or indirectly) a pathway deep within the brain. Both acute and prolonged drug use causes pervasive changes in brain structure and function that persist long after the individual stops taking the drug. The ‘addicted’ brain is different than the non addicted brain in terms of structure and function. ‘A metaphorical switch in the brain seems to be thrown as a result of prolonged use’ Leshner (1997)…. That addiction is tied to changes in brain structure and function is what makes it, fundamentally, a disease’ Implications: We shouldn’t marginalize addicts, but rather we should be trying to treat them. Similarly, incarcerating individuals wont work.

Answer 352

Mesocorticolimbic dopamine system: the ventral tegmental area and areas that project to and from it. 1. Mesolimbic pathway: VTA to the limbic forebrain, esp. the nucleus accumbens, but also involves the amygdala, hippocampus, and the bed nucleus of the stria terminalis. 2. Mesocortical pathway: VTA to the prefrontal cortex All drugs of abuse stimulate dopamine release in this area (directly or indirectly) (Nestler, et al 2005). Cocaine directly increases DA Alcohol, Heroin, Nicotine indirectly increase DA Also stimulated by food, sex, warmth, and other “natural” rewards.

Answer 353

Alcohol effects endogenous opioids and the mesolimbic dopamine system Endogenous opioids activate µ-receptors located on the GABAergic neurons, this inhibits GABA transmission, and ultimately leads to increased dopamine release. β-endorphin GABA DA Acute alcohol triggers β-endorphin release, resulting in activation of µ-receptors on the GABAergic neurons in VTA (inhibits GABA) Alcohol also inhibits glutamate effects on GABA neurons - - decreasing GABAergic activity in the VTA. Alcohol also directly increases the activity of dopamine neurons. Conclusion - - dopamine release is involved in alcohol admin.

Answer 354

The key steps in fast synaptic transmission. An action potential, initiated at the axon hillock of the presynaptic cell, propagates to, and depolarizes the presynaptic terminal. Voltage-gated calcium channels in the presynaptic terminal are activated by this depolarizing wave, allowing a rapid and localized increase in calcium at the active zone. This increase in calcium results in the rapid fusion of neurotransmitter-filled vesicles to the presynaptic membrane which then release their contents via exocytosis. The neurotransmitter molecules diffuse across the synaptic cleft where they bind to ligand-gated ion channels which gate the influx of ions into the postsynaptic dendritic bouton. This influx of ions generates an excitatory or inhibitory postsynaptic potential depending on whether the channels are excitatory (glutamatergic) or inhibitory (GABAergic). The neurotransmitter molecules are then taken back up into the presynaptic terminal by active mechanisms. This entire process, from the initiation of the action potential in the presynaptic terminal to the generation of a postsynaptic potential, takes only a couple of milliseconds.

Answer 355

Originally believed that DA release meant experience of pleasure, or the rewarding aspects of a stimulus - Oversimplistic Natural rewards (food, sex, water) also stimulate the mesolimbic pathway (good for survival). DA is also triggered when drug-related cues are present (BEFORE drug is taken).

Answer 356

Activation of the mesolimbic DA system seems to have numerous roles Attributes incentive salience to drugs and drug-related cues (Robinson and Berridge, 1993), so influences behavioural arousal How quickly DA is activated seems to be involved in attributing more incentive salience – so you’ll interpret stimuli as more reinforcing or rewarding Some research suggests that DA is very important in the acute reinforcing effects of psychostimulants but has a more general activational function with other types of substance. For example, lesions of the mesocorticolimbic DA system block the reinforcing effects of cocaine and D-amphetamine but DA lesions in the nucleus accumbens does not block heroin or alcohol self-administration.

Answer 357

Individuals who are dependent on drugs often report they ‘want’ drugs but no longer ‘like’ them. Think back to the DSM 5 criteria. Craving, strong urges… despite wanting to cut down, no longer finding the drug appealing. Robinson and Berridge (e.g. 1993, 2008) developed the incentive salience model of addiction. - They argued that dopamine was important in the process of WANTING the drug but not liking the drug. Dopamine function attributes incentive salience to a stimulus (e.g. drug), determining how important it is to the individual (how much they want it)

Answer 358

The mesocorticolimbic pathways also links with the hippocampus and amygdala This means that the drug’s reinforcing effects are linked to learning and memory

Answer 359

Established learned associations can develop, e.g. between the drug and drug-related cues. When the individual comes into contact with the drug cue, this may trigger activity in the mesocorticolimbic pathway which increases likelihood of alcohol/substance related behaviour.

Answer 360

Positive affective, motivational-incentive theory: substances produce positive effects via direct actions on the nervous system, and these actions underlie motivation to continue substance use. Particularly in the short-term, sensitisation to a substance’s positive effects could result in a priming dose transiently motivating goal-directed substance behaviour (Stewart et al., 1984; Stewart & de Wit, 1987).

Answer 361

Negative Reinforcement: as dependence develops, withdrawal symptoms (UR) are experienced, and cues (CS) associated with substance administration will elicit withdrawal-like responses (CR). Animals made dependent on a drug will work hard to obtain more of the drug to alleviate withdrawal

Answer 362

Volunteers on methadone maintenance were given a low dose of naloxone to precipitate opiate withdrawal symptoms (reduced skin temperature due to vasoconstriction - “goose flesh”) At the same time, they were presented with a peppermint odour in a conditioning chamber. So they’re linking the smell (cue/conditioned stimulus) with withdrawal. No temperature effect during the pre-training session (control: trials 2 and 3), During training, naloxone produced a sharp drop in skin temperature. During test trial (with no naloxone), the conditioning stimulus (peppermint odour) alone produces a temperature drop similar to the unconditioned response

Answer 363

GD behaviour: priming activates positive expectancies regarding substance use. Substance administration will reflect the current value of the substance (de Wit & Dickinson, 2009). Habit-like: a cue (drug cue, stress, priming drink) will trigger substance administration with little reflection (automatic) Stimulus - Response - Outcome (SR association)

Answer 364

``` Decision making Assigning value Emotional regulation Learning and memory Inhibitory control ```

Answer 365

Loss of control ‘compulsion’ may not simply be attributable to the subcortical reward circuits. Human imaging studies have identified a key involvement of the prefrontal cortex. PFC is thought to regulate limbic reward systems but also be involved in higher-order behaviours EXECUTIVE FUNCTIONING / IMPULSIVITY

Answer 366

Goldstein and Volkow Addiction cannot be explained by dopamine in the limbic brain pathways alone. Dopamine involvement in drug addiction is likely to be mediated by means of functional and structural changes in the circuits that are modulated by dopamine, including the frontal cortex.

Answer 367

``` Neurotoxicity. Structural loss. DA loss. - volumetric loss of frontal lobes Cocaine Alcohol Heroin Methamphetamine ```

Answer 368

Inhibitory control can also be called ‘response inhibition’. This is an executive function (so a type of cognitive process) which allows people to inhibit (stop/withhold) dominant behavioural responses. Our ability to stop, change or delay an inappropriate response (Logan et al, 1984) has a large overall with our self control (90%: Baumeister). There is a persistent desire or unsuccessful efforts to cut down or control alcohol use (DSM-V diagnostic criteria)– so perhaps AUD/SUD is a problem with inhibitory control? Inhibitory control can be measured using a number of tasks e.g. anti-saccade, stop signal, Stroop Deficits in response inhibition in those with severe AUD, but also heavy drinkers (Smith et al., 2014).

Answer 369

Deficits in response inhibition in childhood are predictive of illicit drug use Nigg et al. (2006) Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders. J Am Acad Child Adolesc Psychiatry. 45(4):468-75. Poor response inhibition predicts the transition from heavy use to dependence Rubio (2008) The role of behavioral impulsivity in the development of alcohol dependence: a 4-year follow-up study. Alcohol: Clinical and Experimental Research. 32(9):1681-7. Response inhibition predicts drinking (but not the other way around!) Fernie et al (2013) Multiple behavioural impulsivity tasks predict prospective alcohol involvement in adolescents. Addiction. 108: 1916-1923 People with stimulant use disorder had abnormalities in frontal cortex, so did their drug naive sibling Ersche et al (2012) Abnormal Brain Structure Implicated in Stimulant Drug Addiction. Science. 335 (6068): 601-604).

Answer 370

Cocaine dependence is associated with volumetric loss in pre-frontal and frontal cortex. Furthermore, the duration of drug use was associated with loss (Ersche et al., 2011 Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain. 134:2013-24) What happens in relapse and abstinence? Poor inhibitory control predicts relapse to drug / alcohol use in some studies, but not in others. Similar with abstinence. (Zamir & Robbins (2014) Fronto-striatal circuits in response-inhibition: Relevance to addiction. Brain Research. 1628: 117-129)

Answer 371

Cause and effect often works both ways: impairments in inhibitory control, decision making etc may be a risk factor for A/SUD. As chronic use develops, substance use is also likely to lead to these impairments. Brain models argue that changes that occur in our brains over repeated drug use challenges an addicted person’s self-control and interfere with their ability to resist intense urges to take drugs. This is why drug addiction is also a relapsing disease

Answer 372

It has led to over investment: 41% of addiction funding is for basic neuroscience with a further 17% developing ‘biological cures’. Few new drugs have been developed based on neurobiology The most widely used drugs in addiction? Methadone Replacement Treatment Nicotine Replacement Therapy

Answer 373

V OLITILE U NCERTAIN C OMPLEX A MBIGUOUS

Answer 374

``` Reduced sense of control and autonomy Continuous flux and change Instability within the environment Uncertain future More complex ways of working Emergence of task focused and punitive culture Greater conflict with peers ```

Answer 375

Robust stress policy and wellbeing assessment Occupational health processes and support Robust HR and H&S processes to support employee wellbeing Annual staff survey Bi-annual stress survey Authority peer-review processes

Answer 376

``` S tatus C ertainty A utonomy R elatedness F airness ```

Answer 377

Dreaming is defined as mental activity during sleep We encounter around 5 dream episodes a night 7.53 billion dreamers – 35 billion dreams every 24 hours Dreams can last for between 15-40 minutes per episode Humans spends about 2 hours dreaming every night = 6 years across a lifetime

Answer 378

Could REM sleep episodes be the physical correlates of dreams? Could dreams represent the replay of the day’s events – critical mechanism in forming memories? 80% awakenings (REM) vs 7% non-REM = dream recall Non-REM are isolated experiences but REM sleep are full narratives REM sleep and dreaming can be dissociated Antidepressants abolish REM sleep but not dreaming Cortical lesions abolish dreaming but not REM sleep

Answer 379

Current thinking – dreaming present throughout the whole sleep cycle Participants wore EEG caps while sleeping in a sleep lab Woken at different times depending on EEG reading Asked – where they dreaming/recall of details Non-REM – reports of dreaming but largely impossible to remember Correlation between dreaming and low-frequency brain waves Occurred in the posterior cortical zone (back of brain) Dubbed ‘Hot Zone’ Allowed prediction of dreaming – with 87% accuracy

Answer 380

Whole brain, from brain stem to cortex, is active during dreams Most dreams occur during REM sleep Limbic system is responsible for emotions in both waking and dreaming Amygdala – associated with fear Cortex – responsible for content – visual cortex is especially active Parts of the frontal lobes are the least active

Answer 381

Men: Dream more often about men, physical aggression and sexuality Meta-analyses of studies of differences in waking life: Men – more aggressive Continuity between waking life and dreaming supported Women: Equal proportion of male and female More aggression turned inward Themes of depression Women – more vulnerable to depression Women recall dreams more often than men Gender specific dream socialisation may explain this finding More motivated by others to share dreams Women tend to report more nightmares than men for age range 10 – 60 years

Answer 382

18 hours in a 24 hour period spent in REM sleep before birth 70% of sleep during first few months of life – reducing to 30% at 6 months Intellectual maturity (age 8 or 9) before dreams resemble adulthood Children dream about animals more than adults More likely to have fantastic dreams whilst adults contain elements of reality

Answer 383

Children have nightmares far more than adults Nightmares peak at about 3-6 years old New responsibilities and expectations Very vivid imagination Children can cry during nightmares REM sleep – paralysis prevents any other indication Can be remembered the next day

Answer 384

Occur during stage 3 and 4 (slow wave) sleep Apparently terrified – thrash around and scream Do not respond to comfort Do not have images associated with them Not remembered the next day Fear reaction when transitioning between stages of sleep (often slow wave and REM sleep)

Answer 385

Evaluated association between dreams and dream reports 148 elderly people (age 75.8 yrs) compared with 151 young people (age 22 yrs) Young – more explicit statements of emotion Verb tenses – elderly shift between past and present tense Visual sense – younger made more reference to sight

Answer 386

The number of days with dreams is decreased in older persons. These findings have been in part related to a small reduction of REM sleep among older persons Reduced dream recall in elderly people could also be associated with memory decrements characteristic of senescence or of a failure of initial memory consolidation Other researchers have interpreted such findings as the sign of a diminished interest in dreams and not as a consequence of a weakening of the memory. More recent studies suggest that recall of dreams is an acquired cognitive skill that depends in part on the development of the neural network responsible for spatial perception in the parietal lobes and that children's clearer memory of dreams is linked to their visuospatial capacities

Answer 387

Early civilisations – a medium between earthly world and the Gods Greeks and Romans – dreams had prophetic powers Numerous theories have been proposed to explain the mystery behind dreams Psychological theories – Freud and Jung – Threat-simulation theory – Expectation Fulfilment theory Neurobiological theories – Activation-synthesis theory – Continual activation theory

Answer 388

Freud Centred around notion of wish fulfilment Latent content – deep unconscious wishes or fantasies Manifest content – superficial and meaningless Instigation often found in the events of the previous day Jung Content relates to dreamer’s unconscious desires Provide revelation that could resolve emotional or religious problems or fear

Answer 389

Ancient biological defence mechanism Evolutionary advantage – capacity to repeat potential threatening events Trains the neurocognitive mechanisms for threat perception and avoidance Rehearsal = better preparation Historically rewarded reproductive advantage

Answer 390

Dreaming allows emotional arousals to be discharged Frees up space in the brain to deal with tomorrows emotional cues Allows instinctive urges to remain responsive Prevents false memories being created Provides an explanation for why dreams are usually forgotten

Answer 391

Dreams don’t actually mean anything Electrical brain impulses that pull random thoughts from our memories Humans construct ‘dream stories’ on waking to give sense to content However… Realistic aspects of human dreams Indirect experimental evidence that other mammals also dream Theorised that dreams do serve a purpose

Answer 392

The function of sleep is to transfer information into long-term memory. NREM sleep processes conscious (declarative memory) REM sleep processes unconscious (non-declarative memory) Dreaming are a by-product of this data transfer process They are caused by random memories that the brain retrieves to keep all parts of working memory continually active Dreaming and REM sleep must be controlled by different brain mechanisms

Answer 393

Dreaming is believed to be a mental health activity – helps diffuse strong emotions Peace of mind when awake – dreams with positive effect Anxiety in waking - nightmares Dreams often provide clues to the nature of mental illness Schizophrenics have poor quality dreams usually about objects rather than people Depression is less frequent in people with vivid dreams Nightmares in bipolar disorder provides clues to mood – dreams about death represent a shift to a manic episode

Answer 394

Lucid dream – one in which the individual knows they are dreaming Lucid dream - represents a brain state between REM sleep and wakefulness Increased activation of parts of the brain normally suppressed Some are able to alter the direction of dreams to a preferred outcome Lucid dreaming therapy: Stop nightmares from occurring/reoccurring Help with phobias (exposure therapy)

Answer 395

Some of the most common chromosome abnormalities seen in live-born infants, children and adults.

Answer 396

Pre 1900 – X chromosome thought to be “accessory”, like the appendix. 1903-1920s – X and Y related to sex, but unsure how. 1940s-50s – first descriptions of sex chromosome disorders. Evidence to suggest that some occur during meiosis (sex cell division).

Answer 397

Deletion – part of a sex chromosome is missing. Monosomy – one whole chromosome is missing. Trisomy – an additional sex chromosome.

Answer 398

45, X One of the most common sex chromosome abnormalities. First described in the 1950s. Genetically female. One X chromosome. Estimates of prevalence vary – 1 in 4000 live births, 1 in 2500 live births. 99% pregnancies lost before 28 weeks. Diagnosed prenatally, early childhood or adolescence when puberty does not occur.

Answer 399

Low birth weight. Short stature – growth hormone from 4y can help achieve normal adult height. Increased risk of congenital heart defects. 4-5 x greater risk of premature mortality due to heart complications. Common kidney problems. Underdeveloped reproductive system – infertility.

Answer 400

Extra skinfolds on the neck – webbing. Puffy hands and feet due to edemas. Downward slanting eyes. Broad chest with widely spaced nipples.

Answer 401

Prenatally – ultrasound scans that may show heart or kidney issues, or swelling of limbs and neck Amniocentesis Early Childhood – physical features e.g. neck webbing, short stature Later childhood - lack of menstruation and/or spontaneous puberty Karyotyping – prenatally or from blood sample to confirm chromosome number

Answer 402

Lack of spontaneous puberty and secondary sex characteristics – additional oestrogen treatments needed. Intelligence usually average or above average. Although increased risk of nonverbal learning disorders. Problems with visuo-spatial skills, executive functions and social skills – similar to a nonverbal learning disability (Rovet, 1995). Delayed language development. ADHD?

Answer 403

Structural abnormalities – narrow palate. Pre-speech anomalies – lack of sucking, munching, swallowing (Mathiesen et al, 1992). Van Borsel et al (1999) – 128 people with TS 2.4-58.8 years old. Stuttering, articulation problems. 25% received speech therapy for delayed language development. But normal IQ ranges? We will think about this more later!

Answer 404

“A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development - DSM-V. Behavioural issues. Blurting out answers in class. Failing to attend to social cues. Handling frustration with aggression or impulsive manner. Russel et al (2006) – 50 people with TS, 24% ADHD (1.3% average for non-TS) Hyperactive/impulsive subtype – most non-TS girls have combined subtype. Why? – Learning and cognitive deficits in TS predispose people to developing this subtype of ADHD? (Kirk et al, 2005). Consideration – Comorbidities. e.g mood disorders (Soendergaard, et al 2016).

Answer 405

47,XXY First sex chromosome disorder to be described. - Klinefelter et al (1942, 1959). Genetically male Two X chromosomes and one Y chromosome Estimated 1 in 575-1000 live births 25% ever diagnosed? Association with increased maternal age (Jacobs et al, 1998). Often only discovered during investigations for infertility. KS not hereditary.

Answer 406

Taller than average – 6ft plus (Chang et al, 2015). Long, slender limbs. Pear shaped hips, female fat distribution. Gynaecomastia - breast development. Scant body and facial hair. Small testes and penis during childhood; small testes during adulthood. Inadequate testosterone production – supplements. Infertility. 2D:4D ratio similar to females Marker of prenatal testosterone exposure.

Answer 407

``` Decreased muscle tone during infancy. Mild neuromotor deficits. Delayed speech and reading. Limited vocal sounds in infancy. Trouble with words and sounds that are similar. Begin talking later . ``` Behavioural issues.

Answer 408

IQ slightly lower to average compared to siblings or controls. Extra help with reading and spelling at school – 60-85%. Increased likelihood of dyslexia.

Answer 409

Shy, reserved and lacking confidence. Difficulties in social situations. Anxiety, depression and social withdrawal. ADHD and autism spectrum? Tartaglia et al (2010) - 57 young people XXY, age 6-21 tested for attentional and social problems via questionnaires. Greater internalised distress; 38% met criteria for ADHD inattentive subtype. van Rijn et al (2008) – 31 XXY people – interpersonal behaviour and autism spectrum questionnaires. Higher incidence of autism traits. Greater social distress, closer to psychiatric levels than control. Specific difficulties in expressing negative emotions, refusing a request.

Answer 410

Unclear picture – due to small samples? Miller et al (1988) Evidence for arson in KS – but N=4 No evidence of increased crime rate in KS (Witkin, 1976) – N=19 Stocholm et al (2012) – Danish Cytogenic Central Register, N=934 KS, conviction rates between 1978-2006. Greater incidence of conviction overall. Greater incidence of conviction for sexual abuse, burglary, arson and “others”. Still significant but reduced when controlling for socioeconomic factors e.g. education, fatherhood, cohabitation, retirement Why?

Answer 411

Turriff et al (2017) Qualitative exploration of men’s experience of KS – N= 310 Infertility and its psychological impact: sadness, loss Bullying because of physical appearance: height, small testes, muscle tone Cost, side effects and trouble finding information about testosterone supplements Academic and social challenges Positive: empathy, resilience, stronger relationships

Answer 412

Speech and language issues – speech therapy Practice mouth sounds, strengthen mouth and jaw, play, nursery rhymes and games to make it fun, short and clear instructions, encourage repeating it back Early intervention from educational psychologists KS boys are often passive and withdrawn, so offered less educational support than disruptive classmates Children sometimes labelled “naughty”, “disruptive”, “slow learners”, “poor performers”. Evaluation from educational psychologists Support plans, working with families too ADHD or autism spectrum traits Anxiety and depression, body image, self-esteem. E.g. de Vries et al (2019) – greater incidence of anxiety and depression in TS and KS than controls. Counselling, psychotherapy, psychosocial help. Genetic and psychological counselling for infertility.

Answer 413

Small samples – N’s of 4, 19,51…how generalisable is this? How can we separate out the effect of diagnosis? Prenatal vs postnatal – does this affect outcomes? See Gunther et al (2004). Difference in environment because of knowing. Extra support from younger age. Patience, empathy, understanding, supportive family. Consider use of growth hormone in TS from 4y. Overreliance on quantitative data. Cross-sectional, correlational data. “This syndrome is associated with….”. Ascertainment bias . X chromosome differences help us to study social disorders and ASD Comorbidities and genetic influence Extra chromosome = extra risk? IQ testing – how reliable is this? IQ used to describe outcomes of sex chromosome disorders. Not always correlated with IQ test scores. Different types of “intelligence”? Validity of tests and ethics of using them in these situations?

Answer 414

Ascertainment bias occurs when the type of participant studied does not represent the cases originating from the population

Answer 415

Severe cases more likely to present to medical attention. Overall severity exaggerated? Implications for information provided to families and genetic counselling. Especially important for incidental diagnosis. Riggan et al (2020) – overly medicalised, innacurate, outdated information (criminality, intellectual development)

Answer 416

CT – Computerised Tomography uses X-rays to scan the brain from different angles and uses computer software to construct these images. As you can see from these images, CT provides far less detailed images of soft tissue than MRI, meaning this type of scanning technique is very rarely used for neuroscience research, particularly if the goal is to accurately depict and detect structures in the brain (which it often is!).

Answer 417

PET – Positron Emission Tomography uses radioactive tracers injected into the patient to allow for the detection of positrons (the counterpart of the electron) emitted by the tracer, which allows for the construction of these images. It’s usually combined with either CT or MRI scans to add further structure.

Answer 418

TMS – Transcranial Magnetic Stimulation (or rTMS) uses magnetic fields to induce electric current changes in particular regions of the brain. TMS can activate or inhibit brain function. TMS is non-invasive, quick, and provides a good alternative to all other methods discussed so far. Because it’s so different and allows researchers to actively change the function of the brain (rather than just measure function), it allows for improved investigation into brain mechanisms and function. It’s primary pitfalls are that it can produce adverse effects (such as fainting, dizziness, and even seizures), although these are rare. Another, bigger, issue is that like EEG, TMS is mostly limited to altering the function of the cortex; however, with newer technologies (for example newer coils) this is likely to change in the future.

Answer 419

- Increases (red) and decreases (blue) in REEG of AUD patients compared to controls, with most changes seen in occipital and left parietal regions (regions which coordinate visual perception and spatial attention). - Exp.1 = Low-theta wave activity in frontal and parieto-occipital regions associated with craving upon cue exposure. Exp.2 = Activity actually predicted changes in cigarette craving. - Those with IGD show decreased P300 amplitudes and increased P300 latency (indicating attention allocation), similar to that found in alcohol and cocaine addicts. - high users and addicts of virtually all drugs and behavioural addictions have changes (possibly deficits) in their reward structures, which can influence things like attentional bias and impulsivity.

Answer 420

Right amygdala volume reduced 23% (left 13%) in cocaine addicts vs controls, while the hippocampus was reduced ~5%. Amygdala (blue), hippo (pink). Research from pathological gamblers appears less decisive, but there is still some evidence of reduced volume, particularly in the putamen (in the basal ganglia), thalamus, and hippocampus. WM volume was found to be reduced in AUD patients compared to controls; however, this was massively moderated by whether patients were treatment-seeking or treatment-naïve. Specifically, treatment-seeking patients had much greater WM reductions than those who had never received treatment – one interpretation of this is that WM reductions cause cognitive and behavioural deficits which cause suffering, and thereby encourage patients to seek treatment. Related to this is the finding that number of days abstinent was also a moderator, with longer abstinence being associated with closer WM volume in AUD patients as control participants. This indicates that abstinence may aid recovery of WM. M-A on stimulant drugs dependant patients (primarily amphetamines/meth and cocaine) and grey matter volume. The solo brain image shows the regions of significantly reduced grey matter in addicts compared to controls, with the worst effected areas being the ventromedial PFC, anterior thalamus, and the pregenual anterior cingulate – regions which are typically associated with regulation of emotional, cognitive, and behavioural responses, as well as the processing of rewarding cues (such as drugs). They also found negative correlations between years of drug use and GM volume, meaning... However, these results (as well as the results of the other studies we’ve looked at) don’t tell us about causality – does the addiction cause the changes in brain structure, or do people become addicts partly because of their different brains? Well, this study also reports data showing MRI scans of stimulant addicts and their non-user siblings versus controls. The red indicates increased volume, blue = decreased. The results showed that both siblings (addicts and non-users) had greater GM volume in important subcortical areas (putamen, hippocampus, amygdala) compared to controls. The addicts additionally showed significantly smaller volume in the PFC (compared to controls) which was not found in their siblings. Together these findings indicate that some people may have brain structures which predispose them to addiction (such as larger reward- or emotion-related structures in the brain like the amygdala and putamen), and those subset who do become dependent then suffer further structural changes in, this time in the PFC which controls executive functions and oversees things like self-control and decision-making.

Answer 421

- In a RT task, healthy controls showed trial-by-trial adjustment of their behaviour (as you’d expect of top-down, cognitive control), indicated by higher positive numbers. This behavioural adjustment was correlated with BOLD activation in the rDLPFC. Both adjustment and rDLPFC BOLD responses was dampened in meth abusers (note: the image depicts control subjects’ activation). Suggests meth addicts have reductions in both brain activation and behaviour in adjusting to external events. In AUD patients they found that in the absence of the alcohol cue, alcoholics showed more activation to negative than to positive images and greater activation than controls to negative images. When the IAPS images were presented with the alcohol cue, there was a decreased difference in activation between the positive and negative images among the alcoholics, and a decreased difference in response to the negative images between controls and alcoholics. In conclusion, the alcohol cues may have modulated cortical networks involved in the processing of emotional stimuli by eliciting a conditioned response in the alcoholics, but not in the controls, which may have decreased responsiveness to the negative images And we see the same pattern of results in a separate analysis within the same study. The key regions here were the hippocampus, parahippocampal gyrus and lingual gyrus. Similarly we find that cocaine dependent patients show lower BOLD activation than controls to pleasant vs. neutral images, in regions such as Nacc, DMPFC, and caudate nucleus (again regions implicated in emotional and reward processing, as well as attentional allocation). When completing a reward-based decision task, meth addicts who relapsed showed reduced activity on large, risky wins relative to smaller, safer wins, compared to meth addicts who remained abstinent. This may indicate that those who relapsed react similarly to all rewards, regardless of magnitude or risk. Further modelling showed that a lack of differentiation in BOLD responses between reward types predicted onset of relapse.

Answer 422

Cocaine addicts were injected with craclopride (a radioligand which competes at DA receptor sites with endogenous DA) and underwent a PET scan while watching either neutral (nature video) vs a cocaine-cue video. In the cocaine vs neutral video, they found reduced ligand binding in the dorsal but not the ventral striatum, indicating that DA uptake was high in the dorsal region, a region implicated in habit learning and action initiation. This DA uptake also positively correlated with self-reported craving. Virtually identical results were found using almost identical methods by another study in the same year, again studying cocaine addicts, but this time the key region identified was in a more specific region of the dorsal striatum: the putamen. Again the researchers found that DA binding was positively correlated with self-reported craving. Same results but this time with AUD patients and DA uptake in the ventral as opposed to the dorsal striatum. Dorsal = manages the shift from goal-oriented behaviour to habitual Ventral = manages stimulus-response (habitual) behaviour This activation relates to resting-state glucose metabolism in those areas. They also found the gaming addicts showed higher impulsivity and that this was correlated with the severity of their gaming addiction. Caudate nucleus = learning, motivation, reward processing Insula = emotions and feelings (such as cravings)

Answer 423

Findings across imaging methods are relatively consistent Both cortical (executive function; control) and sub-cortical (emotion; reward; attention) structures important Differences in brain structure and function between addicts and healthy controls Evidence that differences both pre-date addiction and are exacerbated by it Caveats remain regarding how addiction is formalised (choice vs. brain disease) Whatever the framing, the brain is pivotal in understanding and potentially treating addiction

Answer 424

Consuming addictive substances is a positive experience because they increase the release of opioids in the brain – which reinforces substance use Over time, people become tolerant to the effects; the positive experiences occur only when they consume more and more of the substance This can lead to physical dependence on the substance, and experiencing withdrawal symptoms when they cease consumption

Answer 425

Most alcohol drinkers have experienced mild withdrawal symptoms – had a hangover In people with an alcohol use disorder, symptoms are more severe and can include: Tremors, sweating, nausea, vomiting Convulsive activity Delirium tremens – disturbing hallucinations, delusions, tachycardia, hyperthermia – they can be lethal

Answer 426

Because alcohol affects multiple aspects of brain activity, treatments have been developed that work in different ways: 1. Pairing drinking with negative effects (Disulfiram) 2. Affecting GABA levels (Acamprosate) 3. Blocking the opioid receptor system (Naltrexone)

Answer 427

Disulfiram (marketed as Antabuse) blocks the enzyme aldehyde dehydrogenase (ALDH) When a patient who has taken Disulfiram has an alcoholic drink there is a build up of acetaldehyde which leads to a Disulfiram ethanol reaction (DER)…

Answer 428

``` DER produces unpleasant physical reactions like: Nausea Vomiting Tachycardia Dizziness ```

Answer 429

Before treatment, AUD patients tend to hold positive beliefs about how drinking alcohol affects them In addition, their high tolerance levels mean they are unlikely to suffer immediate negative consequences when consuming alcohol frequently This means, that without treatment, their experiences following drinking are unlikely to change their beliefs Knowing that drinking leads to unpleasant effects quickly—because Disulfiram blocks the liver’s ability to break down the ALDH into acetaldehyde—changes patients’ beliefs about the effects of alcohol…

Answer 430

Alcohol enters the brain via the bloodstream and acts as a GABA agonist and a glutamate antagonist Because GABA is an inhibitory neurotransmitter increasing the release of GABA reduces action potentials frequency In contrast, Glutamate is an excitatory neurotransmitter, so by blocking the effects of Glutamate (acting as an antagonist), alcohol reduces action potential frequency. In effect, the brain is down-regulating GABA and up-regulating glutamate Both of these effects depress brain activity; this is not the same as saying drinking alcohol makes people feel depressed

Answer 431

Unlike Disulfiram, which has psychological effects that reduce consumption, treatments such as Acamprosate work pharmacologically, to reduce craving for alcohol Acamprosate is recommended in combination with counselling as its effect is to reduce craving for alcohol (thought to be associated with GABA) Acamprosate affects GABA levels in the brain At some point, we might decide we need help, so we stop drinking… As GABA crashes down, glutamate activity increases significantly In high concentrations, glutamate is neurotoxic Acamprosate works by reducing the craving induced when we stop drinking

Answer 432

Skinner et al. (2014)’s systematic review compared the efficacy of Disulfiram to various control groups. They included 22 trials (N = 2414) patients Patients given disulfiram did better than control groups on a range of outcomes: total abstinence proportion of abstinent days mean days of alcohol use no relapse time to first heavy drinking day, 3 or more weeks of abstinence

Answer 433

Blind design (K = 7) = patients don’t know they are on Disulfiram Open label design (K = 15) = patients know they are on Disulfiram For blind designs, there was no difference in outcome between the Disulfiram groups and control groups For open label designs, there was a difference between the Disulfiram groups and control groups

Answer 434

Rosner et al. (2010) tested the effectiveness of Acamprosate against placebo in patients with alcohol dependence They found 24 studies (N = 6915) patients Acamprosate reduced risk of heavy drinking by 86% relative to placebo Patients who were given Acamprosate suffered Diarrhoea more than the control patients The authors conclude that Acamprosate is effective and safe, although small effects

Answer 435

``` Opioids are a class of substances that derive from opium and affect the opioid receptor system. Opioids is a term that is synonymous with opiates; the main reason for the two terms is that opiates usually refers to substances derived from opium, while opioids covers substances like diamorphine (heroin) which are synthetic derivates of opiates ```

Answer 436

All opioids produce their effects by affecting opioid receptors in the brain These receptors respond to endogenous (i.e., made within our body) opioids as well as exogenous (i.e., made outside of our body) opioids like heroin. The most famous endogenous opioid is endorphin released following physical activity, sex and other pleasurable activities

Answer 437

Heroin (diamorphine) is a synthetic opioid In the short-term, injecting heroin into a vein will lead to a rush of euphoria (the high) followed by a sense of calm This effect occurs due to heroin being a sedative For people unused to takin heroin it can lead to nausea Heroin also reduces breathing Repeated injection of Heroin leads to the development of tolerance to the drug (the same as repeated alcohol consumption) The higher your tolerance, the more heroin you have to inject to feel the effects (the same thing happens with alcohol) Over time, people become physically dependent on Heroin; if they do not inject Heroin they suffer withdrawal symptoms

Answer 438

Patients with an opioid use disorder usually suffer severe withdrawal symptoms when they don’t ingest heroin Increased restlessness – pacing, fidgeting Watery eyes, runny nose, sweating Fall asleep for several hours Wake up to chills, shivering, sweating, nausea, vomiting leg cramps

Answer 439

Patients who have been become addicted to drugs like Codeine and Fentanyl may suffer from the following withdrawal symptoms: Sleep disturbance Vomiting Severe cravings

Answer 440

The simplest way to treat an opioid use disorder is to prescribe a treatment, such as methadone or naltrexone, that blocks the opioid receptors.

Answer 441

Methadone is an opioid which is prescribed to heroin users Methadone works in the same way as heroin, by interacting with the opioid receptors Because Methadone works in the same way as illegal opioid it is possible to get addicted to it! One advantage of taking Methadone is that it is prescribed, which means patients do not have to pay drug dealers for it like Heroin For some people, they take Methadone to reduce their withdrawal symptoms, while waiting for their drug dealer

Answer 442

Naltrexone blocks the effects of heroin by blocking opioid receptors in the brain A downside of being prescribed naltrexone is that as well as blocking the effects of alcohol (or heroin) on your brain it also stops pain killers (like morphine and codeine) working too

Answer 443

Amato et al. (2013) reviewed 23 RCTs testing the effectiveness of methadone against placebo While there was no difference in study completion There was also no difference in abstinence rates; this means being given methadone did NOT increase abstinence

Answer 444

Gowing et al. (2017) reviewed 10 studies (6 RCTS, 4 prospective cohort studies) comparing effectiveness of opioid antagonists (naltrexone) against other approaches to manage withdrawal symptoms The authors were uncertain if peak withdrawal is more severe in treated patients compared to other groups They also warn that clinicians should warn patients of the possibility of suffering delirium in the first day

Biological psychology (year one) Flashcards

(469 cards)