spindles and transients - sleep phenomena, mechanisms and substrates

Electroencephalogram, Spindles and K complexes

Sleep

• The default state

• Active Process

• Requires synchronizers

• Sleep Spindles, K Complexes

Raphe promotes sleep

Locus coeruleus promotes wakefulness

*so sleep control is distributed across centers

The reticular formation also promotes wakefulness

Slow-Wave Activity: -- Spindles: 7 - 15 Hz ; Wax and Wane -- Delta: 1 - 4 Hz -- Slow Osc. .5 - 1 Hz

Stages of sleep form cyclical pattern

Sleep Spindles

• Compared to alpha rhythm !!

• One of the earliest described events

• Hallmark of Synchronization

• Requires an oscillator

Klimesch VO: BioIII 7

The approximate location of the three cuts for the human brain areshown below.

Thalamus

Cerebellum

Encephale isole‘

Midpontine pre- trigeminal

Cerveau isole‘

Norm

al sle

ep-w

ake

cycle

i nc lu

di n

g R

EM

SW

S

Sle

ep-w

ake

c ycl e

with

out R

EM

THALAMUS

REVA

A

M

VL

VP LP

LGN

MGN

Pu

G. prae-centralis

G. post-centralis

Gyri frontales

Gyri orbitales

Gyritemporales

Gyriparietales

Corpus striatum

Thalamocortical Network

Ctx

RE TC+

+

+

-

Thalamocortical spindle circuitry

Modified from Steriade and Llinás. Physiol.Rev. 68:649-742, 1998.

T type calcium channel genes in thalamus

Courtesy of E Talley, D Bayliss & E Perez-Reyes

1H

1G

1I

Post inhibitory rebound in thalamic relay neurons

Vm

hT

-60

-70

-80

1

0

100 ms

IPSP

T channels reprimed

Ca2+-depende

nt rebound

burst

threshold

Th-cx

Th-cx

L-circ

L-circRE

RE

Aff

Dendro-dendr.

Cortex

Thalamo-cortical reentrant loops. Steriade, M. (1999). Coherent oscillations and

short-term plasticity in corticothalamic networks. TINS, Vol. 22 (8), 337-344.

Basic Circuitry:

Cortex

RE Dorsal Thal. = Relay Nuclei

‚Secondary neurons‘

Th-cx

Th-cx

L-circ

L-circ

RE

RE

Aff

Dendro-dendr.

Cortex

1,2 Afferent brainstem input to Th-cx (1), Activation of RE and Cortex (2)

Th-cx

Th-cx

L-circ

L-circ

RE

RE

Aff

Dendro-dendr.

Cortex

3 Excitatory processes in Cortex; Inhibition of primary L-circ; Inhibition of other RE cells

Th-cx

Th-cx

L-circ

L-circRE

RE

Aff

Cortex

The resulting effect is that during time 4, Th-cx are again under inhibitory control from L-circ neurons and, at the same time are activated from cortico-thalamic cells. Thus, only strong (converging and/or amplified) cortical feedback will trigger another excitatory activation wave into the cortex in time 5.

4 Excitatory feedback response from cortex. Disinhibition of primary L-circ neurons. Inhibition of secondary Th-cx neurons.

The strong inhibition of the secondary Th-cx

cell may lead to low threshold spikes

(LTS) and, thus, to a 10 Hz oscillation.

Th-cx

Th-cx

L-circ

L-circRE

RE

Aff

Cortex

5 The primary Th-cx cell may start a new excitatory burst into the cortex. At this stage (because released from the L-circ inhibition), a new afferent input will have a strong effect.

The secondary Th-cx cells remain under inhibition

RESULT: Center-surround ‚on-off‘ effect with a resulting strong focal activation of cortical target neurons.

Summary of findings: Afferent brainstem activation is missing and cortical activation is strong:

- Th-cx cells are hyperpolarized and oscillate with spindle frequency Note that a depol. current pulse during maximal hyperpol. leads to high frequency bursts. The result is increased oscillatory cortical activation leading to Delta activity.- The effect of increased cortical activation is even larger if stimulation patterns are oscillatory

Th-cxL-circ

RE

Missing brainstem afferents

Cortex Th-cx hyperpolarized,Sleep spindles

SLEEP: Spindles and Delta

Spindle oscillations in thalamus

A M PA /N M D A R

G A BA RA

TC

nR t

-

+

Thalam us

C ortex

IPSP

Rebound Burst

EPSP & Burst

200 m s

20 m

V

timing

RE Cell Rapidly bursting type

A Mathematical model

Foundations II - Neuroimaging

TC Cell modulation by RE cell

A Mathematical model

Propagation of Spindles

Ontogeny of Spindles

• EEG maturation

• Posterior Dominant

• Anterior spread

• Amplitude decreases with age

• Two ditinct frequency bands seen

K Complexes

Paroxysmal Events

K Complexes

• stage 2 sleep, arousing stimuli. • Loomis et al. (1938); • reason for calling them K complexes remains

obscure • spur of the moment • Knocking

• K complex shows a maximum over the vertex, • also K complexes with an indubitable

maximum over the frontal midline.

• H. Davis et al. - central and frontal K complexes

• Brazier (1949) presumed two distinct generators; these were area 6, corresponding with the vertex, and area 9, corresponding with frontal midline.

• initial sharp component, followed by a slow component that fuses with a superimposed fast component.

• The sharp component is biphasic and not seldom multiphasic.

• The slow component is represented by a large slow wave that may exceed 1,000 msec in duration

POSTS start to occur in healthy people at age 4 years, become fairly common by age 15 years, remain common through age 35 years, and start to disappear by age 50 years.

POSTS are seen very commonly on EEG and have been said to be more common during daytime naps than during nocturnal sleep.

Most characteristics of POSTS are contained in their name. They have a positive maximum at the occiput, are contoured sharply, and occur in early sleep (stages I and II). Their morphology classically is described as "reverse check mark," and their amplitude is 50-100 V. They typically occur in runs of 4-5 Hz and are bisynchronous, although they may be asymmetric. They persist in stage II sleep but usually disappear in subsequent stag

Positive occipital sharp transients of sleep

Also called vertex waves or V waves, these transients are almost universal. Although they often are grouped together with K complexes, strictly speaking, vertex sharp transients are distinct from K complexes. Like K complexes, vertex waves are maximum at the vertex (central midline placement of electrodes [Cz]), so that, depending on the montage, they may be seen on both sides, usually symmetrically. Their amplitude is 50-150 V. They can be contoured sharply and occur in repetitive runs, especially in children. They persist in stage II sleep but usually disappear in subsequent stages. Unlike K complexes, vertex waves are narrower and more focal and by themselves do not define stage II.

Vertex sharp transients