PBL 4- Epilepsy

Question 1

What makes up myofilaments

Answer 1

Myofilaments:
	- Contain protein 
		○ Actin
		○ Tropomyosin
		○ Troponin
	- Thick Filaments
Myosin

Question 2

What happens at the neuromuscular junction?

Answer 2

• Ach released at NMJ
  
  • AP generation in muscle cell
  • Ca influx
  • Myosin-actin interaction
    Contraction occurs

Question 3

What is the A-motorneuron?
Where are they located?
What is the structure?

Answer 3

• Large diameter myelinated
  
  • Final neurons located in the ventral horn of the spinal cord
  • Their axons form the ventral root

Question 4

What is a motor unit?

Answer 4

• The smallest functional unit for movement
  
  • Consists from:
    ○ Single a-motor neuron
    ○ Its axon
    Plus all the muscle fibres innervated by the neuron

Question 5

What is a motoneuron pool?

Answer 5

A group of neurons (a column) that innervate one muscle

Question 6

What is The neuromuscular junction

Answer 6

• The synapse between the motoneuron axon terminal and the muscle fibre
  The arrival of the action potential along the neuron to the terminal causes release of a neurotransmitter

Question 7

What degrades/ rate limits the Ach in the NMJ?

Answer 7

• Cholinesterase

Question 8

What kind of receptors bind Ach in the NMJ?

Answer 8

Nicotinic ion channels

Question 9

What allows the muscle to be a “smooth” contraction?

Answer 9

• Temporal summation of action potential leads to tetanus

Ceases when stimulation ceases or when fatigue begins

Question 10

Drugs that effect the neuromuscular junction

Answer 10

- Curare 
		○ ACH receptor blocker 
		○ Results in Paralysis of the muscle
	- Physotigmine 
		○ cholinesterase inhibitor
		○ potentiates effects of Ach
		○ Muscle spasm at overdose
	- Organophosphates
		○ Cholinesterase inhibitor
	- Botox
		○ Ach Release Blocker
Results in paralysis of muscle

Question 11

Which Motor Neurone innervates a muscle spindle/ intrafusal fibres?

Answer 11

• Gamma motor neuron

Intrafusal

Question 12

Which motor neuron innervates an extrafusal fibre

Answer 12

Alpha motor neurons

Question 13

What does a Golgi tendon do?

Answer 13

Detects tension

Question 14

What does a muscle spindle do?

Answer 14

Detects changes in muscle length

Question 15

What is a reflex?

Answer 15

• Responses to sensory stimuli without participation or contribution of consciousness

Question 16

What are the key features of a motor reflex?

Answer 16

• They are elementary acts of behaviour
  
  • Stimulation of a given output produces determined and predicted output
  • Performed without conscious control
  • In a reflex the afferent input strictly determines output- there is NO contribution of will.

Question 17

Where is the primary motor cortex located?

Answer 17

• M1
  
  • Area 4
    Pre central gyrus

Question 18

What are Betz cells?

Answer 18

• Pyramidal cell neurons in the primary motor cortex
  
  • Send axons down the corticospinal tracts to the anterior horn cells of the spinal cord
  • Lie in the deep area of the cortex
    Responsible for initiating voluntary and conscious movement.

Question 19

Damage to the capsula interna would result in what clinical signs?

Answer 19

Paralysis and sensory loss on the CONTRALATERAL side

Question 20

Why does the membrane potential occur?

Answer 20

Separation of oppositely charged ions

Question 21

What is responsible for the membrane potential?

Answer 21

• Inside is negative compared to outside
  
  • Determined by the concentration gradient of Potassium
    Loss of K results in a negative charge

Question 22

What ensures that the membrane potential remains constant?

Answer 22

Active transport pumps (Na/K ATPase) ensure that the electrochemical equilibrium does not occur

Question 23

What is a nerve terminal?

Answer 23

A secretory machine that is dedicated to rapid rounds of NT release

Question 24

What is hyperpolarisation?

Answer 24

A refractory period where no new action potential can be granted

Question 25

What ion causes the depolarisation phase?

Answer 25

Na influx

Question 26

What ion causes the repolarisation phase?

Answer 26

K efflux

Question 27

What causes hyperpolarisation?

Answer 27

- Inhibitory post synaptic potential - Prevents excitation or terminates action potential - Restores voltage to original value - Cell becomes more negative inside Through influx of CL- and Efflux of K+

Question 28

What causes Depolarisation?

Answer 28

- Excitatory post synaptic potential - Cell becomes less negative inside - Influx of NA and Ca No potassium leaving the cell

Question 29

Different broad types of Ion Channel types

Answer 29

- Voltage-gated - Ligand-gated (extracellular ligand) - Ligand-gated (intracellular) Mechanically gated

Question 30

Voltage Gated ion channels What are they made from? How are they gated? What type of signal do they give?

Answer 30

- Pore forming proteins - Gated: opening is voltage dependent ○ Flow is according to pre-existing electrochemical gradients - High flow selectivity - High throughput ○ Thousands of ions flow per second ○ Large and brief electrical signal - High variety Complex range of signals

Question 31

Domains of voltage gated Na, Ca and K

Answer 31

- S4 family = the pore forming subunit - Built on a motif of 6 TM (S1-S6) segments - S4 = the Voltage sensor - Pore Loop domain = S5-S6 Forms complex with auxiliary sub units

Question 32

What is the purpose of the auxillary sub units of a voltage channel?

Answer 32

- They are associated with the channel | - Modulate gating, kinetics, intracellular trafficking, current amplitude

Question 33

How are voltage gated channels modulated?

Answer 33

- Voltage ○ Activation and inactivation kinetics depending on cell type and channel sub type - Activation gate ○ Responds to voltage changes - Inactivation Gate ○ Na channels - close the gate - Auxilary subunits - Protein phosphorylation/dephosphorylation ○ Action of protein kinases and phosphatases ○ Na phosphorylation slows its inactivation - Binding of toxins and drugs Ion channel subtype specificity

Question 34

Voltage gated K channels

Answer 34

- Involved in the REPOLARISATION phase - Terminates action potential Rate of closing affects excitability ( ability to rapidly fire)

Question 35

Therapeutic targets for K channels?

Answer 35

- When action potential firing is decreased in CNS depression ○ K channel inhbitors - When pathological hyperexcitability K channel activators

Question 36

Voltage Gated Calcium Channels How is it classified? What role does it have how is it modulated?

Answer 36

- Classification is according to the Alpha 1 subtype - Critical role in NT release, synaptic plasticity and PAIN Complex modulation

Question 37

Therapeutic targets for N-type calcium channels

Answer 37

- Associated with Pain - Opiates Derivatives of conotoxins= analgesics

Question 38

``` Voltage Gated Na channels Describe the gates How is it regulated? What role does it have? How does it appear in the different phases of the AP? ```

Answer 38

- Has 2 gates - Activation gate - H = Inactivation gate - Regulated by Phosphorylation - Opening is responsible for the rising phase of the action potential - In the repolarisation phase the activation gate is open but the inactivation gate is closed - Resting = activation is closed and inactivation is open Depolarisation phase = both open

Question 39

Clinical significance of Na channels

Answer 39

- Important in transduction of noxious signals -> pain pathways - Local anaesthetics like lidocaine block Na conductance by binding to the inner portion of the Na channel - Targets for many epileptic drugs Targets for many toxins

Question 40

Tetrodotoxins

Answer 40

- TTX- producing bacteria - Prevent the Na flow ○ Bind to the outside of pore independent of voltage status- alpha subunit Most Na channels in CNS and PNS are TTX sensitive

Question 41

Voltage gated Chloride channels General structure what role does it have?

Answer 41

- 9 proteins- glial and neuronal - Has two pores - Channels are arranged as dimers - Separate (fast) or common gating - opening/closing of 2 pores Alterations associated with juvenile epileptic syndrome, gliomas.

Question 42

Ionotropic receptors

Answer 42

- Not a transporter - If no ligand they are closed - Multimeric protein Opening typically requires binding of more than one neurotransmitter molecule

Question 43

What are the types of Ionotropic Neuro transmitters

Answer 43

``` - Excitatory ○ Nicotinic (Ach, Da, NE) ○ 5HT3 (5HT) ○ AMPA, NMDA (Glutamate) - Inhibitory GABA a (GABA) ```

Question 44

GABA a Receptors What type of receptors? role?

Answer 44

- Ligand gated ion channels - Responsible for hyperpolarisation (CL influx, K efflux = decreased depolarisation) Terminates or prevents initiation of action potential

Question 45

Cation-selective ligand gated ion channels | What type of receptors?

Answer 45

- Neuronal ACH receptors - Glutamate NMDA (NA and Ca) Glutamate AMPA (Na)

Question 46

What happens in Seizure initiation?

Answer 46

- Burst of action potentials called a paroxysmal depolarising shift Abnormal and excessive synchronisation of neighbouring populations of cortical cells

Question 47

How is a Seizure propagated? | How is it mediated?

Answer 47

- Ie partial seizure that spreads - Activation of nearby neurons - Loss of surrounding Inhibition - Aberrant excitability associated with epileptic discharge mediated by voltage gated and ligand gated ion channels May also be a result of genetic defects in channels

Question 48

What are the Key features of seizure generation

Answer 48

- TOO MUCH EXCITATION ○ Leads to sustained, overt depolarisation and excessive discharge ○ Mediated by ions - inward NA and Ca currents ○ Mediated by NT - Glutamate - TOO LITTLE INHIBITION ○ Leads to defects in hyperpolarisation ○ Mediated by ions : inward CL and outward K Mediated by NT = glutamate

Question 49

What is the paroxysmal depolarisation shift?

Answer 49

- Characteristic sustained depolarisation with repetitive spiking (burst firing) Occurs synchronously in a large group of neurons

Question 50

Role of channels in epilepsy

Answer 50

Voltage gated NA and CA channels are major AED targets ○ Inhibitors of these inhibit high frequency repetitive spiking GABA a receptors = second major AED targets ○ Drugs that ENHANCE INHIBITION are used as anticonvulsants ○ Prevent AP propagation and seizure spread ○ Phenobarbitol ○ Inhibitors of GABA degradation or reuptake Others ○ Antagonists of NMDA receptors- to prevent excitation ○ Activators of voltage gated K channels Blockers are powerful convulsants

Question 51

Describe general Brain metabolism/ energy requirements

Answer 51

- The brain depends on a large and stable blood supply - It has no effective way to store oxygen or energy - High metabolic demand is met by a high blood flow to deliver energy substrates and oxygen Local blood flow rates vary depending on neuronal activity

Question 52

What is the main source of ATP for neurons?

Answer 52

Mitochondrial oxidative Phosphorylation

Question 53

Why is ATP so important in the brain?

Answer 53

- Maintains Ion gradients - If you lose ATP there is an inhibition of the Na, K ATPase pump - Destruction of ion gradients Results in energy failure and neuronal death

Question 54

What is Phosphocreatine?

Answer 54

- Can be used transiently to regenerate ATP - Used under ANAEROBIC conditions - Used in skeletal muscle and brain - Used when: ○ Intense muscular effort or neuronal demand A decrease in phosphocreatine is seen prior to a decrease in ATP in anaerobic conditions because brain would utilise pcr as needed

Question 55

What is The blood brain barrier:

Answer 55

- Specialised system of capillary endothelial cells - Enclosed by end feet of astrocytic cells - Separates circulating blood and CSF - Is a physical and metabolic barrier - Protects brain from harmful substances while supplying required nutrients - Tight junctions disrputed in many CNS pathologies - Provides the rate limiting factor in permeation of drugs

Question 56

Molecular trafficking through BBB | ie how to things go through the BBB?

Answer 56

- Paracellular pathway ○ Through the tight junctions ○ Small, water soluble - Transcellular ○ Lipid soluble ○ Usual pathway for drugs - Transport proteins ○ Glucose, amino acids, nucleotides ○ Also has efflux transporters Cyclosporin a

Question 57

``` Glucose and the brain Use: Storage: Transport: How can it go wrong? ```

Answer 57

Use: - In the fed state glucose is the main fuel for the brain - Brain completely oxidises glucose to CO2 and water - Required for normal brain function and development Storage: - No storage of glycogen in neurons - Some glycogen stores in astrocytes Glucose transport: - facilitated diffusion - GLUT 1 transporter = BBB endothelial cells and astrocytes - GLUT 3 transporter = Neuronal specific - High affinity and high capacity glucose transport (facilitated diffusion) How it can go wrong? - GLUT1 deficiency syndrome- defective glucose transport across BBB- low glucose in CSF in presence of normal glycaemia ○ Infantile seizures and developmental delay Abnormal expression and/or activity of GLUT1 in chronic epilepsy = decreased glucose uptake

Question 58

What is GLUT1?

Answer 58

Glucose transporter in BBB endothelial cells and astrocytes

Question 59

What is GLUT 3?

Answer 59

Neuronal specific glucose transporter

Question 60

What is the glucose transporter for BBB endothelial cells?

Answer 60

GLUT1

Question 61

What is the neuronal specific glucose transporter?

Answer 61

GLUT 3

Question 62

When are alternative brain fuels used?

Answer 62

- When energy demands exceed glucose supply brain can utilise lactate and ketone bodies - During: ○ Development ○ Hypoglycaemia (Ketones) ○ Starvation Situations of intense neural activity

Question 63

``` Ketone Bodies Where are they produced? How are they utilised? What is their importance How can this be used clinically? ```

Answer 63

Produced: - In the liver in response to starvation Utilisation: - Up regulation of transport across BBB during starvation Importance: - Development Uses: A ketogenic diet can be an effective treatment of epileptic seizures in GLUT 1 deficiency syndrome- will use ketones rather than glucose

Question 64

Oxidative phosphorylation Is oxygen required? What is the process?

Answer 64

Oxygen: - Necessary for this process Process: - Glucose metabolised to pyruvate via glycolysis - Pyruvate is then completely oxidised in the mitochondria to CO2 Produces a lot of ATP

Question 65

Anaerobic glycolysis Is oxygen required? What is the process?

Answer 65

Oxygen : - Used when oxygen is limiting Process: Cells redirect the pyruvate generated by glycolysis away from mitochondrial oxidative phosphorylation by generating lactate

Question 66

What is Aerobic Glycolysis

Answer 66

- Conversion of glycose to lactate when oxygen is PRESENT - Much less efficient than oxidative phosphorylation for generating ATP Process can exist in tumours - Warburg effect

Question 67

``` Lactate What are its uses? When does it increase in its use? What is the role of the neuron? sources of lactate? ```

Answer 67

``` Uses: - Underlies the energetics of diverse brain activities ○ Long term memory function ○ Sensory processing ○ Pathophysiological conditions ``` ``` - Increases in response to: ○ Hypoglycaemia ○ Ischaemic events ○ Stress - Could be present in the resting brain however research isnt sure ``` Role of neurons: - Can transport and oxidise lactate Sources of lactate when brain activity is increased: - Net influx of lactate from blood to brain - via lactate transporters - Increase in local aerobic glycolysis (increased neuronal/astrocyte glucose uptake) - Astrocyte- neuron lactate shuttle hypothesis ○ Lactate generated from astrocyte glycogen breakdown Transported into neurons for use

Question 68

What is the response to falling plasma glucose?

Answer 68

- Prolonged and severe hypoglycaemia is rare in humans | The brain is very tolerant to changes in glucose

Question 69

What happens in the Early stages of hypoglycaemic coma What does the EEG show? What changes do you see in oxygen, energy, phosphocreatine and ATP levels?

Answer 69

- Normal oxygen and energy levels - Oxygen consumption continues - Eeg shows slow waves and polyspikes - Levels of phosphocreatine and ATP remain NORMAL unless there is respiratory depression

Question 70

What happens in Prolonged and severe Hypoglycaemia?

Answer 70

- Some loss of ATP = approximately 25-30% of control levels - There is not a complete energy loss - loss of ATP correlates with onset of flat (isoelectric) EEG - Neuronal damage results from oxidative stress - Neuronal death takes several hours Mechanisms for damage/death: Increased neuronal release of glutamate leads to oxidative stress

Question 71

What is Oxidative stress: When does it occur? what does it lead to?

Answer 71

- Results from imbalance between levels of reactive oxygen species ROS and antioxidants - ROS such as peroxides and radicals are derived form inherent aerobic metabolism of oxygen - Under normal circumstances cells are able to balance the production of oxidants and antioxidants resulting in the redox equilibrium - Oxidative stress occurs: ○ Cells are exposed to excess levels of ROS and/or ○ As a result of antioxidant depletion - Leads to: ○ Mitochondrial damage ○ DNA damage Ultimately leading to energy failure and death

Question 72

``` Hypoxia Causes: Effects: Mechanisms to avoid metabolic failure? What is a clinical risk of treatment? ```

Answer 72

Causes: - Systemic/local blood circulation defects eg Stroke Effects: - Not tolerated for long periods due to insufficient energy supply to brain - Activation of short and long term adaptive mechanism ○ Activated by oxygen sensing systems ○ Activation depends on duration and severity of deprivation ○ Does this to avoid metabolic failure and risk of oxidation toxicity Mechanisms to avoid metabolic failure: ○ Increase in local blood supply (autoregulation of cerebral blood flow, increases cardiac output, vasodilation) ○ Shut down of non-essential energy consuming mechanisms ○ Changes in gene transcription and protein synthesis to stimulate production of RBC and angiogenesis Risk: Excessive reoxygenation = risk of cell injury by increased inflammation and oxidative stress

Question 73

How does energy failure occur in hypoxia/ischaemia?

Answer 73

- Lack of oxygen - Utilisation of Phosphocreatine - Rapid ATP exhaustion - Blocking of ATPase (NA/K) - Collapse of ion gradients Rapid and large depolarisation

Question 74

Events during brain ischaemia

Answer 74

- ATP failure - Collapse of ion gradients - Massive depolarisation due to influx of NA and CA and efflux of K - Increased Glutamate released - NMDA receptor activation - Increased CA influx Increased acidification (lactic acidosis)

Question 75

Explain the link between Ischaemia and lactic acidosis

Answer 75

- The Ischaemic brain has no O2 so uses anaerobic glycolysis to meet the brains energy requirements - This leads to production of lactate - Excessive accumulation of lactate aggravates brain damage during ischaemia due to enhanced lactic acidosis - The intensity will depend on glucose sotres There is NO lactic acidosis in hypoglycaemia- THERE IS NO GLUCOSE PRECURSOR TO MAKE LACTATE

Question 76

What are the secondary mechanisms of ischaemic cell death?

Answer 76

- intracellular calcium overload ○ Due to increased calcium influx from increased glutamate release ○ Oxidative and metabolic stress leading to cell death ○ This occurs via mitochondrial failure, disruption of cell membranes and changes in gene transcription - Inflammatory reactions ○ Microglia - Blood Vessel leakage - Brain oedema BBB breakdown

Question 77

What is the time course of hypoxic-ischaemic brain injury?

Answer 77

Immediate: 2-10 minutes - Necrotic cell death ○ Due to Na overload and increased glutamate ``` Delayed: 6-72 hours - Delayed necrotic and apoptotic cell death ○ Ca overload and oxidative stress ○ Mitochondrial dysfunciton ○ Inflammation BBB failure ```

Question 78

What brain sites are most vulnerable to cerebral ischaemia?

Answer 78

- Hippocampal CA1 | All middle laminae of the cortex

Question 79

Describe what happens to the brain metabolism during the ictal phase of a seizure:

Answer 79

- Increased metabolic rate (250%) = hypermetabolic - Increased cerebral blood flow to supply glucose and nutrients - Very small perturbation of tissue energy state and ion homeostasis (ATP remains stbale - 99%) Increased lactate production during and as a result of a seizure (due to increased demands for glucose)

Question 80

Describe the changes in metabolism during the INTERICTAL PERIODS of a seizure

Answer 80

- DECREASED requirement - lower than normal glucose uptake and blood flow - Altered GLUT 1 expression at BBB endothelium Decreased glucose uptake within epileptic areas/foci

Question 81

What is 2DG?

Answer 81

- Assessment of brain glucose metabolism - indirect measure of neural activity - It competes with glucose for entry into cell and accumulates - It cannot be catabolised PET scan with flurescent derivative ( 18F)FDG can identify low metabolism seizure sites in interictal period

Question 82

What are the cellular events in response to an epileptic insult?

Answer 82

Repeated and prolonged seizures can lead to irreversible damage and cell loss and reorganisation of synaptic networks First minute to hours after status epilepticus insult: - Cell loss - Hippocampal sclerosis ○ Excessive activation of excitatory glutamate receptors which results in glutamate excitotoxicity ○ Oxidative stress leads to damage of mossy cells and loss of GABAergic inhibition - Astrocyte proliferation and dysfunction as a result of neuronal damage - Inflammation and BBB failure - Moderate lactate acidosis compared to ischaemia ``` Several hours to months after seizure insult - Disease progression - Long term damage - Chronic increase in calcium ○ Changes to gene expression initiating synaptic remodeling events ○ Eg neurogenesis - Acquired channel dysfunction BBB dysfunction ```

Question 83

The links between BBB function and seizures?

Answer 83

- Seizures can cause BBB failure leading to BBB leakage - BBB failure can lead to seizures ○ Acquired BBB defects such as head trauma and brain tumours ○ Multiple drug resistance can be due to defects in transporters in the BBB ○ Metabolic BBB defects such as GLUT1 deficiency syndrome Systemic and immune triggers.

Question 84

General function of areas of the brain | Cerebrum:

Answer 84

- Conscious thought processes - Intellectual functions - Memory storage and processing Conscious and subconscious regulation of skeletal muscle contractions

Question 85

General function of areas of the brain | Thalamus:

Answer 85

Relay and processing centres for sensory information

Question 86

General function of areas of the brain | Hypothalamus:

Answer 86

- Center controlling emotions - Autonomic functions Hormone production

Question 87

General function of areas of the brain | Midbrain:

Answer 87

- Processing of visual and auditory data - Generation of reflexive somatic motor responses - Maintenance of consciousness

Question 88

General function of areas of the brain | Pons:

Answer 88

- Relays sensory information to cerebrum and thalamus | Subconscious somatic and visceral motor center

Question 89

General function of areas of the brain | Medulla oblongata:

Answer 89

- Relays sensory information to thalamus and to other portions of the brain stem Autonomic centers for regulation of visceral function (cardiovascular, respiratory and digestive system activities)

Question 90

General function of areas of the brain | Cerebellum:

Answer 90

- Coordinates complex somatic motor patterns | Adjusts output of other somatic motor centers in brain and spinal cord

Question 91

Which brain areas are responsible for attention?

Answer 91

- Dorsolateral prefrontal cortex - Ventrolateral prefrontal cortex - Parietal cortex - Dorsal anterior midcingulate cortex - Striatum: caudate and putamen - Cerebellum

Question 92

If a patient showed Hemineglect- which lobe of the brain is effected? Which side is most likely?

Answer 92

- Parietal association cortex | In particular the right hemisphere

Question 93

What would deficits in the orbitofrontal cortex present as?

Answer 93

- Disinhibition - Altered personality - Lack of empathy - Socially inappropriate behaviour - Reactive aggression Impaired "mind theory"

Question 94

What would deficits in the Dorsolateral prefrontal cortex present as?

Answer 94

- Reduced attentional control - Perseveration - Impaired "executive" functions Working memory , sequencing, planning, creativity, reasoning

Question 95

What would deficits in the Medial prefrontal cortex present as?

Answer 95

- Decreased motivation - Apathy - Akinesia - Impaired detection of mismatches or errors

Question 96

What is consciousness?

Answer 96

- State of awareness of self and the environment (space/time) - Being able to orientate and respond to new stimuli appropriately - Arousal and wakefullness ○ Depends on the functioning of cerebral hemispheres and the reticular activating system of the brainstem - Content and cognition: emotions ○ Depends on a functioning cerebral cortex ○ Confusion, delirium, stupor - Unconsciousness is a lack of awareness/responsiveness - Narrow meaning of consciousness = being awake

Question 97

What is an EEG? Minimal amount of electrodes? Where does it get contributions from?

Answer 97

- Recording of electrical signals from the scalp - Minimal electrodes is usually 18 - Waves come from synchronous contribution from a very large number of neurons - Contributions from both post synaptic potentials (excitatory and inhibitory) and action potentials - Cannot record EEG from a small amount or a single neuron

Question 98

Types of brain waves from an EEG:

Answer 98

- Delta wave ○ Slow wave sleep ○ Coma ○ < 4hz - Theta ○ Drowsiness ○ 4-7 hz - Alpha ○ Relaxed wakefulness with CLOSED eyes ○ 8-15 hz - Beta ○ Active wakefulness ○ 16-30 hz - Gamma ○ Usually Artefact by muscular activity ○ 30-100 Hz

Question 99

What describe the waves seen in Slow wave sleep

Answer 99

- High amplitude and low frequency - Synchronised EEG Delta waves

Question 100

Describe the waves seen in wakefulness

Answer 100

- High frequency and low amplitude - Desynchronised EEG Beta waves

Question 101

What brain waves would you see if you were awake with closed eyes?

Answer 101

Alpha waves

Question 102

In Slow wave sleep- how to thalamic neurons fire?

Answer 102

- They fire in bursts | Frequency is the same as delta waves

Question 103

In awake and REM sleep how do thalamic neurons fire?

Answer 103

- Neurons fire single spikes in alpha frequency Excitatory influences are then transmitted to cortex via thalamo-cortical projections

Question 104

Slow cortical waves are of what origin?

Answer 104

Thalamic

Question 105

What is the difference between EEG and fMRI

Answer 105

EEG: - based on direct measurements of electrical activity of electrical activity of the brain - Excellent temporal resolution - Poor spatial resolution fMRI: - Indirect measure- based on consequences of metabolic activation - Poor temporal resolution (few seconds to mins) - Good and improving spatial resolution

Question 106

REM Sleep: | What are EEG waves like?

Answer 106

- Rapid eye movement - EEG waves are similar to wakefulness - Neurons fire single spikes in alpha frequency

Question 107

What is the Lateral Reticular formation? | What is another name for it?

Answer 107

- Parvocellular | - Reflex connection to local cranial nerve nuclei

Question 108

What is the medial Reticular formation? | What is another name for it?

Answer 108

- Magnocellular - Neurons make long ascending and descending axons - Involved in control of: ○ Movement ○ Posture ○ Pain ○ Autonomic function ○ Arousal

Question 109

``` Noradrenergic neurons (In relation to arousal) Where are they located? Where do they project to? What is the function? ```

Answer 109

Location: - Locus coeruleus - Ie bilaterally In the pons Project to: - The spinal cord to modulate autonomic reflexes and pain - To cerebrum: for vigilance and responsiveness to unexpected environmental stimuli and mood

Question 110

``` Serotonergic neurons (In relation to arousal) Where are they located? Where do they project to? What is the function? ```

Answer 110

Located in: - Raphe Nuclei - Midline along the brain stem Project to: - The spinal cord: modulation of AP, HR and Body temp - The Hypothalamus: modulation of AP, HR and Body temp - The Cerebrum: Mood and sleep/wake cycle

Question 111

Cholinergic neurons (In relation to arousal) Where are they located? What is the function? When are Ach levels high and low?

Answer 111

Located: - Pons and Midbrain - Pontomesencephalotegmental complex - Basal nuclei Function: - Influence cortical arousal during waking states and dreaming (REM) Ach Levels: - High during wake and REM sleep - Low during Slow wave sleep

Question 112

Histaminergic neurons (In relation to arousal) Where are they located? What is the function? What effect to antihistamines have?

Answer 112

Located: - Tuberal mamillary nucleus Function: - To help maintain arousal in forebrain Antihistamines: - Cause drowsiness if they cross the BBB

Question 113

Orexin/Hypocretin neurons (In relation to arousal) What is orexin? What is the function? What does a deficit cause?

Answer 113

It is an excitatory Neuropeptide Function: - It provokes wakefulness - Increaes thermogenesis - Increases appetite Deficit: - Causes Narcolepsy

Question 114

Which brain structure modulates sleep? Where is this located? What are the functions? Where does it project to and what role does this have?

Answer 114

The Suprachiasmatic Nucleus - Located in the rostral part of the hypothalamus Functions: - Brains biological clock - Modulate via Retino-hypothalmic tracts - Output controls sleep onset and durations as well as associated bodily changes Projects to: Forebrain - Attention - Emotions - Psychomotor performance Pineal Gland - Melatonin - Suppressed by light Hypothalmaus - Hormonal control - TH, GH, Cortisol - Metabolism - Orexin Brainstem - Sleep/arousal state - AP, HR, respiration

Question 115

What does Melatonin do?

Answer 115

- Involved in light-induced entrainment of sleep cycle | - Secretion suppressed by light

Question 116

What is Orexin? Where is it produced? What does it do?

Answer 116

- Neuropeptides - Produced by dorsal hypothalamus - Control appetite and arousal - Works as a neurotransmitter

Question 117

What cell groups are involved in the Ascending Arousal system? What are the two main cholinergic pathways? What is the end result?

Answer 117

- Monoaminergic cell groups involved: ○ Noradrenaline, serotonin - Cholinergic inputs from pedunculopontine and laterodorsal tegmental nuclei Two main cholinergic pathways: - To the intralaminar nuclei of the thalamus - this then projects widely to the cortex - To the lateral hypothalamic area to join with hypothalamic and basal forebrain cholinergic projections to cortex Results in: massive diffuse cholinergic innervation of cortex

Question 118

What is the inhibitory Surround? | What is the importance of this?

Answer 118

- When excitatory pyramidal neurons send projections to proximal neurons they also activate interneurons adjacent to them - The interneurons are GABAeric and send inhibitory projections to surrounding neurons - This creates an inhibitory surround - The inhibitory surround prevents synchronisation of adjacent neurons - This process is abnormal in epilepsy allowing synchronous firing of neurons

Question 119

What are the characteristics of a partial seizure?

Answer 119

• Occur in a limited part of the cerebral hemisphere • Preceded by an aura • The part of the brain that is involve will determine the symptoms ○ Ie sensory cortex will produce sensory symptoms ○ Motor cortex will cause twitching or stiffening in the opposite side ○ Temporal lobe will cause: hallucinations of smell, taste or sound, dejavu or flashbacks, fear, nausea • Simple = remains conscious • Complex = consciousness is impaired- ability to respond or remember the event ○ Usually display automatisms such as lip smacking ○ Usually begin in the temporal lobe however can arise from anywhere • Can spread to becomes secondarily generalised

Question 120

What are the characteristics of a generalised seizure?

Answer 120

• Involved both sides of the brain from the beginning • Consciousness is impaired immediately • No recollections of the seizures • Can begin as partial seizures that spread • Subtypes ○ Tonic-clonic ○ Absences ○ Tonic ○ Myoclonic ○ Atonic

Question 121

What are the characteristics of a tonic-clonic seizure?

Answer 121

* Lasts from a few seconds to 3-4 minutes * Often the person bites or swallows his or her tongue and may have difficulty breathing- sometimes to the extent that cyanosis occurs * Also signals transmitted from the brain to the viscera frequently cause urination and defecation • Post seizure depression of the entire nervous system ○ Stupor for many minutes after the seizure attack remains severely fatigued asleep for hours thereafter • Initiation of a tonic-clonic seizure □ Majority are idiopathic □ Many have a hereditary predisposition to epilepsy (1 in 50-100) □ Factors can increase the excitability of the abnormal epileptogenic circuitry enough to precipitate attacks ® Emotional stimuli ® Alkalosis caused by over breathing ® Drugs ® Fever ® Loud noises or flashing lights □ Traumatic lesions in the brain cause excess excitability of local brain areas

Question 122

What are the characteristics of absence seizures?

Answer 122

* Begin in childhood * Last less than 10 seconds * Sudden stare and loss of facial expression * Possible rolling of eye upwards * Rhythmic blinking * Can be provoked by hyperventilation * Seizure usually involves much or most of the thalamo-cortical activating system of the brain

Question 123

What are the characteristics of Tonic Seizures?

Answer 123

* Brief generalised stiffening * Last only seconds * Often occur in sleep * Common in those with intellectual disabilities * Causes "drop attacks"

Question 124

What are the characteristics of tonic seizures?

Answer 124

* Sudden loss of tone * If sitting will cause "head nod" * If standing will fall

Question 125

What are the characteristics of myoclonic seizures?

Answer 125

• Appear like a sudden startle • Brief (1 second or less) muscle contraction. • Symptoms may occur in individual muscle or generalise to all muscle groups of the body ○ The latter can result in falling • Associated with systemic diseases such as uraemia, hepatic failure, hereditary degenerative conditions • Associated with mad cow disease