24. Higher Cerebral Functions (HT) Flashcards

Question

How do lesions of the amygdala affect processing of social indicators of fear?

Answer 1

The patient may struggle to recognise and understand facial and vocal expressions of fear.

Answer 2

(Feinstein, 2011): * Studied patient SM, who had Urbach-Wiethe disease with bilateral amygdala damage * IQ, memory, language and perception were unimpaired * But the patient had impaired fear conditioning, recognition of facial expressions, and fear-related social experiments * This was tested by exposing the patient to various animals (e.g. spiders) and scary films, none of which produced indications of fear

Answer 3

* Cortical amygdala is part of the primary olfactory cortex -\> It distinguishes the intensity of odours * The primary olfactory cortex outputs to multiple areas: * Secondary olfactory cortex (orbitofrontal cortex) via the thalamus -\> This distinguishes pleasant and unpleasant smells * Ventrolateral amygdala * Hypothalamus * Entorhinal cortex * Septum * Nucleus accumbens

Answer 4

Hippocampal formation: * Hippocampus * Dentate gyrus * Subiculum * Entorhinal cortex (in parahippocampal gyrus) Hippocampus: * Made of Cornu Ammonis (Ammon’s horn), which has parts CA1-4

Answer 5

* Olfactory system, because it is connected strongly to the entorhinal cortex that is part of the hippocampal formation. * This means that smells can bring about very vivid memories.

Answer 6

Hippocampus

Answer 7

The hippocampus lies in the medial part of the temporal lobe “tucked into” the inferior horn of the lateral ventricle.

Answer 8

Memory (In particular, episodic memory, which refers to the ability to recount past events)

Answer 9

Note that the top input and output on these lists are part of the Papez circuit, which you do need to know.

Answer 10

Long-term potentiation (LTP)

Answer 11

When two neurons synapse onto just one neuron: * If one synapse is active when the other is not -\> Only the first synapse is strengthened * If first synapse is active strongly while the second synapse is active weakly -\> Both synapses are strengthened The second type may explain why we build strong associations between smells and memories.

Answer 12

Associative learning & episodic memory impairment.

Answer 13

* Left hippocampal lesions impair verbal/logical recall * Right hippocampal lesions impair visuo-spatial memory

Answer 14

Posterior hippocampus -\> Memory and spatial navigation: * Place cells support a cognitive map of known location (like taxi drivers remembering a map) and also allow episodic memory * Time cells fire at successive moments in temporally structured events Anterior hippocampus -\> Anxiety-related behaviours: * CA1 neurons connect to the amygdala Note that this mapping is matched in the entorhinal cortex that connects to the hippocampus.

Answer 15

It carries cholinergic fibres to the hippocampus, which are affected in Alzheimer's disease and kickstart the whole process.

Answer 16

Inputs: * From hippocampus via fornix (Papez circuit) Outputs: * To anterior nucleus of thalamus, via mammillothalamic tract (thence to cingulate gyrus) (Papez circuit) * To midbrain tegmental motor structures (pedunculopontine nucleus)

Answer 17

Nucleus accumbens: * It receives input from other limbic areas, including the amygdala and hippocampus * Importantly it also receives dopaminergic input from the ventral tegmental area (this is the indicator of reward) * Onward signalling from the nucleus accumbens does not directly determine outcomes, but it can influence decision-making centres

Answer 18

It is part of the prefrontal cortex.

Answer 19

* Behavioural inhibition * Inhibitory self-control * Emotional regulation The latest opinion is that the orbitofrontal cortex does not only suppress unwanted behaviours and desires, but also encodes a 'value' of certain tasks, taking into account various factors such as difficulty, so that it can provide an updated value for these tasks. Thus, it underlies good and bad choices.

Answer 20

Different neurons have different functions: * Guide behaviours (I will do X to achieve Y) * Signal the hedonic experience of reward * Place a subjective value on a given reward * Detect error * One trial learning

Answer 21

* There needs to be a comparison of the predicted reward obtained from an action with the actual reward obtained * OFC neurons provide VTA neurons with a prediction of the reward of potential choices, and DA neurons in turn project back to OFC with error signals to update them * This drives learning

Answer 22

* Monkeys were shown different cards that indicated either a high-risk, medium-risk or low-risk situation * In the high-risk situation, the monkeys could receive either much more or much less juice than in the low-risk situation * The researchers found two populations of neurons in the OFC: * Economic risk neurons -\> The rate of firing changes depending on the risk of the situation. If the outcome of the situation is known with certainty, there is no difference in firing, regardless of the reward size. * Value neurons -\> The rate of firing changes depending on the reward size, if it is known. If it is not known with certainty (as in the experiment), then there is no change in firing depending on the risk.

Answer 23

* When a single experience is associated with an outcome, without repeated exposure to strengthen this. * An example is taste aversion, where even just one bad encounter with food can put you off for life * The orbitofrontal cortex is responsible for this

Answer 24

Lateral OFC: * Evaluates various decisions independently of each other * Determines an instantaneous, subjective value (e.g. eating this chocolate cake would be great!) * It integrates information from amygdala, hypothalamus, insular cortex (taste, disgust), DA neurons in midbrain (can heighten value attributed to a signal), sensory info from thalamus in order to do this Medial OFC: * Compares these individual options in order to make a choice

Answer 25

* Perseveration [IMPORTANT] -\> This is a deficit in reversal of learning * Inability to change goals and activities * Inability to change problem-solving strategy, etc. * Loss of significance of stimuli (e.g. pain) * Behavioural changes, especially in disregarding laws

Answer 26

* Declarative (explicit) -\> Conscious memory of facts and events * Semantic -\> Factual information (e.g. location of Eiffel tower) * Episodic -\> Personal experiences (e.g. what you had for breakfast) * Non-declarative (implicit) -\> Modes of learning that are non-conscious * Skills -\> Learning skills and habits (e.g. how to ride a bike) * Category -\> Assigning objects/skills in the world into classes for the purpose of generalization, discrimination, and inference (e.g. movie genres) * Priming -\> Where identification of a stimulus is improved by an earlier encounter of that or other stimuli (e.g. being able to complete a partially completed letter once you recognise what it is) * Associative -\> Learning to associate one stimulus with another stimulus (i.e. conditioning). * Non-associative -\> When repeated exposure to a stimulus leads to a change in how intensely it is perceived (e.g. repeatedly hearing a sound in the background may cause you to tune it out).

Answer 27

* Semantic memories (i.e. facts) are likely to be stored in long-term memory * Episodic memories (i.e. experiences) are unlikely to be stored in long-term memory, as the name suggests

Answer 28

* Habituation -\> A decrease in response to a benign stimulus when the stimulus is presented repeatedly. A dog will be aroused when a strange tone is played. If the tone is played over and over, the dog will eventually no longer be aroused by the tone * Sensitization -\> An enhanced response to many different stimuli after experiencing an intense or noxious one. For example, an animal responds more vigorously to a tone of lesser intensity once a painfully loud tone has been played.

Answer 29

* Classical conditioning (Pavlovian) -\> When an conditioned stimulus is associated with an unconditioned stimulus * Operant conditioning -\> When a certain behaviour is associated with a reward or outcome

Answer 30

* Memory is both distributed and localized. * Memory is distributed in that many parts of the nervous system participate in the representation of a single event. * Memory is localized in that a single event involves a limited number of brain systems.

Answer 31

* Patient H.M. suffered from epilepsy and had his hippocampus and parahippocampal regions removed as a possible treatment * The result of this was that he developed severe anterograde amnesia, meaning that he was unable to form new memories * He also had graded retrograde amnesia, meaning that his long-term past memory was more affected most regarding memories just before the operation -\> He was able to recall childhood memories but struggled with memories of the years before the operation * This demonstrated the importance of the hippocampus in forming long-term memories

Answer 32

* It is a syndrome characterised by severe memory loss and confabulation * It is caused by thiamine (vit. B1) deficiency, which is often seen in alcoholics * The mammillary bodies in the Papez circuit seem to be particularly affected * It is reversible

Answer 33

* The Morris water maze involves a hidden platform that mice swim around to find * Within a couple of trials, the mice learn the location of the platform and immediately swim to it * The effect of various interventions on this memory can thus be studied

Answer 34

Long-term potentiation (LTP)

Answer 35

* When the pre-synaptic cell in the hippocampus is stimulated, it leads to increased magnitude of EPSPs * However, this increase in EPSP is maintained for a long time, which is known as LTP

Answer 36

* There are arrays of synapses in the hippocampus * Various synapses within these arrays are strengthened by LTP during memory formation * This leads to the formation of an engram that underlies memory formation

Answer 37

One of the first changes seen in Alzheimer's disease is loss of synapses, which underlies some of the early memory loss.

Answer 38

* Cellular engram (rather than synaptic engram) * Changes in cell excitability (anti-accommodation/ES potentiation) -\> Disproved by the fact that things like anaesthetics do not alter memory * Reverberating circuits * Inhibition

Answer 39

"Consciousness consists of **inner, qualitative, subjective states** and processes of sentience or awareness. Consciousness, so defined, begins when we wake in the morning from a dreamless sleep and continues until we fall asleep again, die, go into a coma, or otherwise become 'unconscious'. It includes all the enormous variety of the awareness that we think of as being characteristic of our waking life." John Searle

Answer 40

* Wakefulness (level of consciousness) -\> How awake or asleep you are * Awareness (content of consciousness) -\>To what extent you are aware of the external surroundings and internal world. For a patient to maintain consciousness, both of these components must be maintained. Essenitally, wakefulness describes the **quantitative** degree of consciousness, whereas awareness relates to the **qualitative** aspects of the functions mediated by the cortex, such as attention, etc.

Answer 41

Sleepwalking, Vegetative state, Seizures

Answer 42

REM sleep has higher awareness than deep sleep, which explains why we might remember some dreams from REM sleep.

Answer 43

Note how REM sleep and being awake are very similar.

Answer 44

* Energy metabolism * Repair and detoxification * Homeostatic synaptic plasticity * Memory consolidation

Answer 45

* A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. * Clinically, a coma can be defined as the inability consistently to follow a one-step command. It can also be defined as a score of ≤ 8 on the Glasgow Coma Scale (GCS) lasting ≥ 6 hours.

Answer 46

Unresponsiveness

Answer 47

Using the Glasgow coma scale.

Answer 48

Contents of consciousness often difficult to evaluate in the clinic because level of consciousness is often reduced at the same time. For example, it is hard to assess someone's alertness when they are asleep.

Answer 49

* Confusion -\> Inability to maintain a coherent sequence of thought and actions * Delirium -\> Agitated, hypersympathotonic, often hallucinatory * Illusion -\> A misperception of sound, sight, or touch * Hallucination -\> A spontaneous endogenous perception

Answer 50

* Vegetative state * Locked-in syndrome * Catatonia

Answer 51

* It is where a patient was in a coma but is has now opened their eyes * There are signs of extensive damage to both cerebral hemispheres: Babinski, decerebrate or decorticate posturing, no response to visual stimuli, no corrective nystagmus in VOR * Autonomic nervous system function often preserved but may show hyperactivity * Yawning, grunting, picking with hands, random limb and head movements may occur In other words, the vegetative state has similarly low awareness to a coma, but it has much greater wakefulness (as shown by the movements, etc.).

Answer 52

Pseudo-coma: * Patients who are awake but selectively deefferented—no means of producing speech or limb, face, or pharyngeal movements * Results from infarction or haemorrhage of the ventral pons, which transects all corticospinal and corticobulbar pathways but leaves RAS intact * Vertical eye movements and blinking (Nn. III and IV) after basilar artery thrombosis often intact

Answer 53

* Generic term for peculiar motor activities associated with major psychosis * Patients appear awake with eyes open but make no voluntary or responsive movements * Spontaneous eye blinking * "Waxy flexibility": limbs maintain their posture after passive movement

Answer 54

* In 1995, the Royal College of Physicians deemed that death was defined as the irreversible loss of brainstem function. * This was because, since the advent of mechanical ventilation in the 1950s, cardiorespiratory function and brain function could be uncoupled, so a neurocentric definition was required.

Answer 55

No, a vegetative state is reversible, brain death is not.

Answer 56

1. Physical quiescence 2. Typical body posture 3. Specific sleeping site 4. Elevated threshold for arousal / reactivity 5. Rapid state reversibility (this differentiates it from coma, etc.)

Answer 57

* Actigraphy -\> Measuring movement over time. Sleep is indicated by periods of immotility. * Standard polysomnography -\> Using EEG (electroencephalogram) and sometimes other techniques to measure sleep

Answer 58

* EEG measures the potential differences between two points on the scalp (or on the surface of the brain). * EEG can be described in terms of frequency (Hz) and amplitude (microvolts) of voltage fluctuations.

Answer 59

* Wakefulness * Low amplitude, fast waves * Stage 1 (Non-rapid eye movement) * Slightly larger amplitude, quite fast waves * Slow eye movements * Stage 2 (Non-rapid eye movement) * Larger amplitude waves * Includes sleep spindles (bursts of activity) and K-complexes (large waveforms) -\> These are characteristic of stage 2 NREM * Stage 3 (Non-rapid eye movement) * High amplitude, slow waves (1-4Hz) * REM (Rapid eye movement) * Appears very similar to wakefulness

Answer 60

Wakefulness in a relaxed subject with eyes closed is differentiated from sleep by the presence of alpha EEG activity in 50% or more of the epoch.

Answer 61

They are characteristic of stage 2 NREM sleep.

Answer 62

* Age * Some diseases (e.g. Schizophrenia and neurodegenerative diseases)

Answer 63

EEG spectral analysis: * EEG signals at different sleep stages feature different wave frequency compositions * To quantatively analyse the contribution of each wave frequency, you can plot a graph of power against frequency.

Answer 64

* AKA brainwaves * These are rhythmic or repetitive patterns of neural activity in the CNS

Answer 65

Thalamocortical system: * Cortical neurons send excitatory projections onto reticular thalamic (RT) nucleus neurons and thalamocortical (TC) neurons * Thalamocortical (TC) also send excitatory projections onto the cortex and the reticular thalamic (RT) nucleus neurons * Reticular thalamic nucleus neurons are inhibitory (GABAergic) and send projections onto the thalamocortical (TC) neurons

Answer 66

* Infra-slow (0.02-0.1 Hz) * Slow: * Slow oscillation (0.2-1 Hz) * Delta (1-4 Hz) * Spindle (7-15 Hz) * Theta (4-10 Hz) * Fast (20-60 Hz) * Ultra-fast (100-600 Hz)

Answer 67

There are no sleep spindles, which explains why there is no spike on this spectrum.

Answer 68

Von Economo first noted that: * Lesions in the anterior part of the hypothalamus often lead to insomnia * Lesions in the brainstem often lead to sleepiness/coma (Gong, 2000): * Expression of c-fos is an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials. * Most of the brain shows decreased activity during sleep, indicated by decreased c-fos, but there are some parts that show increased c-fos, which may indicate that they play an important role in sleep.

Answer 69

Brainstem reticular activating system. Activity is predominantly at cholinergic and aminergic projections up from subcortical nuclei to areas of the cerebral cortex, which maintains its function. These include: * Laterodorsal/pedunculopontine tegmental nucleus * Locus coeruleus * Orexin-producing neurons in the hypothalamus * Basal forebrain

Answer 70

A thalamic population of neurons (Ventrolateral/median preoptic area) predominate during sleep and act by inhibiting the ascending systems that drive the awake state (see previous flashcard). Therefore, there is switching between populations of neurons when going to sleep and waking up, but what drives these switches is yet unknown.

Answer 71

* It is a series of nuclei and pathways in the brainstem that are involved in the maintenance of the awake state. * They project up to the thalamus, hypothalamus and basal forebrain regions -\> These then project to the cerebral cortex to maintain wakefulness (and there are direct projections to the cortex).

Answer 72

* Acetylcholine * Noradrenaline * Histamine * Dopamine * Serotonin * Orexin * GABA GABA, ACh and orexin are mentioned in the spec.

Answer 73

* Hypothalamus * Brainstem * Basal forebrain

Answer 74

(Carter, 2010): * Used optogenetics to stimulate the locus coeruleus neurons. * This lead to immediate sleep-to-wake transitions. (Oikonomou, 2019): * However, stimulation of the dorsal raphe nucleus can lead to promotion of either sleep or wakefulness depending on whether the stimulation is tonic or burst.

Answer 75

MAO inhibitors lead to the almost complete elimination of REM sleep.

Answer 76

* Orexin neurons are found in the **lateral hypothalamus** * They send axons to the entire cerebral cortex, as well as to the brainstem and basal forebrain * Orexin neurons are involved in wakefulness and motivated behaviours (e.g. finding food) * They fire predominantly during wakefulness, and particularly during motivated behaviors

Answer 77

Hypocretin

Answer 78

Lateral hypothalamus releases it onto the cerebral cortex, brainstem and basal forebrain.

Answer 79

Orexin neurons are inhibited by glucose, and activated when glucose is low -\> This makes sense because food seeking behaviours occur when you are awake, so it is useful for orexin to be released then.

Answer 80

* The biological effects of orexin-A are mediated by two G-protein coupled receptors (OX1R and OX2R). * Selective OX2R agonists increased wakefulness and inhibited sleep in rats. * Selective destruction of the orexin neurons results in the symptoms of narcolepsy.

Answer 81

* Narcolepsy is a condition characterised by overwhelming daytime drowsiness and sudden attacks of sleep during the day. * The patients show abnormal cycles during sleep, although patients typically feel refreshed after awakening in the morning. However, sleepiness will rapidly evolve within hours and becomes irresistible (“sleep attacks”) * It has been hypothesized that patients with NC are unable to consolidate wakefulness and sleep because of abnormal sleep-wake regulation. (Chemelli, 1991): * Orexin knockout mice present with a form of narcolepsy

Answer 82

Ventrolateral preoptic area (VLPO)

Answer 83

* The basic principle of the model is that brain regions involved in promoting sleep (e.g. VLPO) and wakefulness (TMN, LC, LH, vPAG) act in opposition to each other, largely through mutual inhibitory connections. * When you are awake, the areas responsible for wakefulness dominate. * When you are asleep, the areas responsible for sleep dominate.

Answer 84

The neurons in the ventrolateral preoptic area (VLPO) release GABA, which leads to sleep.

Answer 85

* They can induce sleep since they potentiate GABAergic transmission. * However, this sleep does not appear to be the same as normal sleep.

Answer 86

* Process S (sleep) -\> Builds up gradually the longer you are awake, applying sleep pressure. * Process C (circadian) -\> Is dependent on the internal circadian clock that drives wakefulness during the day.

Answer 87

Suprachiasmatic nucleus

Answer 88

* The master clock in the suprachiasmatic nucleus is composed of numerous clock cells. * The SCN receives light information by a direct retinohypothalamic tract (RHT) to entrain the clock to the 24-h day * The SCN coordinates the timing of oscillators in other brain areas and in peripheral organs -\> All cells have their own intracellular clocks, but they average out across organs and they are under the influence of the SCN

Answer 89

Retinohypothalamic tract (RHT)

Answer 90

Certain retinal ganglion cells -\> These mean that even people who are blind due to dysfunctional photoreceptors have a circadian rhythm.

Answer 91

* The neurons release glutamate and PACAP onto the SCN neurons * This leads to a cascade that ends in mPer1 expression

Answer 92

* Constant routine -\> Involves keeping the participants under constant conditions, including constant illumination and frequent small meals. * Forced desynchrony -\> The participants are exposed to a light-dark cycle that is much shorter (e.g. 20hr) or longer (e.g. 28hr) than the circadian pacemaker can entrain. So the person sleeps when it is dark but the circadian rhythm is off, so this protocol is good for studying processes at various points in the circadian rhythm. Measurements include core body temperature and melatonin measurements via blood samples or saliva.

Answer 93

* Melatonin * In the pineal gland

Answer 94

* The suprachiasmatic nucleus (SCN) clock regulates the timing of melatonin synthesis and release from the pineal gland * Melatonin has chronobiotic effects and is able to synchronize and reset biological oscillations * Circulating levels of melatonin communicate temporal information to a number of physiological systems and can also feedback to the SCN clock

Answer 95

* Slow wave activity is seen largely during the first half of the night during sleep * The intensity of these waves is a good indicator of how badly the body needs sleep * For example, if you take a nap, then the slow waves will be decreased that night

Answer 96

(Porkka-Heiskanen, 2000) and (Basheer, 2004): * These studies give evidence for adenosine as the substance underlying sleep drive * The hypothesis is that adenosine release increases during waking, building up gradually and leads to inhibition of neural activity in wake-promoting brain regions

Answer 97

People tend to go to sleep earlier and sleep for a shorter amount of time. But it is still debated: Do older adults need less sleep, or they are unable to generate the sleep that they still need?

Answer 98

* About 3/4 of patients with depression experience insomnia symptoms * (Borbély and Wirz-Justice, 1982) -\> One hypothesis for this is the process S deficiency hypothesis, which suggests that this is due to reduced sleep drive

Answer 99

The ICSD-2 lists 81 major sleep disorders in 8 major categories: * Insomnias * Sleep-related breathing disorders * Hypersomnias of central origin * Circadian rhythm sleep disorders * Parasomnias * Sleep-related movement disorders * Isolated symptoms, apparently normal variants and unresolved issues * Other sleep disorders

Answer 100

* Insomnia is clinically defined as difficulty with sleep initiation, sleep maintenance, or overall diminished sleep quality in association with reports of poor daytime functioning (i.e., fatigue, decreased memory and concentration, daytime distress). * Insomnia is a manifestation of a dysregulation of autonomic and central nervous system arousal networks producing hyperarousal. * The insomnia disorders can be either primary or secondary. * Primary insomnias can have both intrinsic and extrinsic factors involved in their etiology, but they are not regarded as being secondary to another disorder. * Secondary forms occur when the insomnia is a symptom of a medical or psychiatric illness, another sleep disorder, or substance abuse.

Answer 101

* Central apnea syndromes include those in which respiratory effort is diminished or absent in an intermittent or cyclical fashion as a result of central nervous system dysfunction. * Primary central sleep apnea is a disorder of unknown cause characterized by recurrent episodes of cessation of breathing during sleep without associated ventilatory effort. * Obstructive sleep apnea in adults is characterized by repetitive episodes of cessation of breathing (apneas) or partial upper airway obstruction (hypopneas). These events are often associated with reduced blood oxygen saturation. Snoring and sleep disruption are typical and common. * Sleep apnea is associated with excessive daytime sleepiness or insomnia. * OSA affects 1 to 6% of adults and 2% of children. Central sleep apnea affects less than 1% of people

Answer 102

* The parasomnias are undesirable physical or experiential events that accompany sleep. * The parasomnias consist of abnormal sleep-related movements, behaviors, emotions, perceptions, dreaming, and autonomic nervous system functioning. * Three parasomnias have typically been associated with arousal from non-REM sleep: confusional arousals, sleepwalking and sleep terrors. * REM sleep behavior disorder is a parasomnia typically associated with the REM sleep stage. RBD involves abnormal or violent behaviors that occur in REM sleep and result in injury or sleep disruption. RBD can occur in narcolepsy, and many patients with Parkinson’s disease have REM sleep behavior disorder. * Recurrent isolated sleep paralysis can occur at sleep onset or on awakening: it is characterized by an inability to perform voluntary movements and may be accompanied by hallucinations