Thalamus/EEG

Question 1

Describe how the thalamus contributes to EEG signals

Answer 1

• the contribution of thalamus to EEG recording is due to thalamocortical connections (thalmus cannot impact EEG DIRECTLY)

Question 2

Slow wave sleep and absence epilepsy

Answer 2

-Slow wave sleep: characterized by a pattern of slow wave oscillation of the EEG at a frequency called the delta wave ~3 Hz
-Absence epilepsy is a type of epilepsy
prevalent in children where the child
has sudden staring spells
-EEG patterns of absence epilepsy and slow wave sleep are similar (~3Hz)
-similarity is that the slow
waves in both cases are caused by the delta frequency oscillations of the corticothalamic circuit

Question 3

Thalamic relay neurons

Answer 3

TR neurons receive input from sensory sytem and relay info to cortex via excitatory glutamatergic synapses onto pyramidal cortical neurons in layer IV of cortex.
-At wake: memb pot=-55mV (when depolarized, they fire APs at high freq)
-Asleep: thalamic reticular neurons inhibit TR neurons by releasing GABA. (TR=-85mV) and they fire bursts of APs riding on top of Ca spike. The Ca spike happens at 3Hz
-The slow Ca spike occurs due to a T type channel that is inactive at depolarization.
-When the cell is hyperpolarized by the thalamic reticular cells, the inactivation gate of Ca opens
-B/c the thalamic relay neuron’s axon
connects to cortical pyramidal cell, the burst of firing of action potentials in the TR cell elicits firing of the cortical pyramidal cell at a δ frequency eliciting the slow wave EEG that is recorded during slow wave sleep.

Question 4

What needs to happen in order for the thalamic relay neurons to fire the slow Ca spikes that give rise to the slow delta wave of EEG during slow wave sleep?

Answer 4

The thalamic relay neurons must be hyperpolarized by inhibitory interneurons in the thalamic reticular nuclei.

Question 5

Can absence-like seizures be induced by pharm treatment of mice if they don’t have the T type Ca channel?

Answer 5

No.
-In contrast: mutant T type Ca channels that alter voltage dependence make it possible for the thalamic relay neurons to fire slow Ca spikes at depolarized resting potentials (~60 mv)–>spontaneous absence like sz.
[Anticonvulsants –valproic acid and ethoxosuximide —for absence epilepsy block T type Ca channels]

Question 6

Thalamocortical circuit activity is
regulated by axons ascending from brain stem from cholinergic, noradrenergic and serotonergic
neurons. Ex of each action.

Answer 6

• If asleep, stim of cholinergic neurons in reticular activating system results in AWAKENING of animal and interruption of slow wave EEG.
• ->stim of these cholinergic neurons leads to release of ACh in thalamus
• Noradrenergic neurons from locus coeruleus relase NE in thalamus.
• ->fight or flight
• Serotonergic neurons from the raphe nuclei release serotonin on thalamus.

All: direct and indirect effect on thalamocortical activity–>det sleep/wakefulness.

Question 7

What does the EEG measure

Answer 7

• small field potentials (voltage change in extracellular medium due to current flow into/out of neuron) at the surface of the skin overlaying the skull
• voltages measured in the EEG are generated by neurons near the surface, and reflect synchronous synaptic input to cortical neurons.

Question 8

Seizure

Answer 8

-an episode of cerebral dysfunction leading to clinical changes in motor, sensory, or autonomic dysfunction
(partial–simple or complex; generalized: absence, myoclonic, tonic clonic, tonic, atonic)

Question 9

Simple vs complex absence seizures

Answer 9

Simple
-impairment of consciousness
-minimal motor activity (eyelid fluttering, blinking)
-90% b/t 5-15s; avg 100/d
Complex:
-impairement of consciousness
-prominent motor activity (myoclonic jerks, automatisms, atonic)
-more common than simple
-automatisms: persistence of an action, mumbling, non-purposeful movements
-autonomic features: pallor, change in HR, RR, mydriasis, micturition

Question 10

Childhood absence epilepsy

Answer 10

• onset 4-8 y (max 6-7)
• frequent absence seizures, often precipitated by HV
• GTC seizures in 30% with onset

Question 11

Juvenile Absence Epilepsy

Answer 11

• Onset 4-30 y (mean 13)
• less frequent absence sz
• duration may be longer with some preserved awareness
• 80% with GTC seizures, 15-25% with infrequent myoclonus

Question 12

Juvenile Myoclonic Epilepsy

Answer 12

• infrequent absence seizures
• GTC and myoclonic seizures (surrounding sleep) are predominant features
• No remission but may be responsive to treatment

Question 13

EEG of typical vs atypical absence

Answer 13

typical:

• normal background
• ictal discharges (abrupt on/off; generalized 3 Hz spike and wave; frontal maximum)
• Spikes may become fragmented and irregular during sleep

Atypical absence:

• often abnormal background with slowing and disorganization
• ictal discharges at 2-2.5 Hz, more irreg)

Question 14

Seizure Treatment

Answer 14

Anticonvulsants:

• ethosuximide/Zarontin–acts on T type Ca current; cheapest and most effective
• Valproic acid (depakote)
• Lamotrigine (lamictal)
• Leviteracetam (keppra) JME

Question 15

Comorbidities in epilepsy

Answer 15

ADHD, learning problems, behavioral issues
So even though they outgrow epilepsy, these comorbidities can lead to long term consequences (less likely to graduate college, get married, etc)

Question 16

Absence seizure

Answer 16

• Brief arrest in behavior lasting 5-10 seconds which may be associated with automatisms or other minor motor movements.
• Characterized on EEG by 3Hz spike and wave discharges
• Treat most commonly w/ anticonv, like Zarontin