Theoretical ReviewK-complex, a reactive EEG graphoelement of NREM sleep: an old chap in a new garment
Introduction
Sixty-seven years after the first description the K-complex (KC)1 has remained an enigmatic element of NREM sleep. It is clear since the first studies2, 3 that the KC has a double character, being on one hand a regular building-stone of NREM sleep EEG and on the other hand a reactive element, elicitable by sensory stimuli. This ‘Janus-faced’ or paradoxical character of KC generated debates on its ‘function’: an elementary arousal-response in NREM sleep4, 5, 6, 7, 8 or a sleep-protective component.9, 10, 11, 12, 13 A third aspect treating KCs as a rebound of the sleep-promoting system to sensory stimuli has been proposed 20 yr ago.14
During the last 20 yr, abundant data have been collected in the topic. This breakthrough was due to the use of averaging- and evoked potential methods15, 16, 17 as well as to the advance in the understanding of sleep neurophysiology.18, 19, 20
Nowadays, KC-research mainly consists of studies on the reactibility of KC-components to different cognitive tasks, used to investigate the information processing during NREM sleep.15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 Other investigations use KCs to study the physiology and pathology of micro-arousals during NREM sleep.34, 35, 36, 37, 38, 39, 40, 41
A trend in this direction incorporates KCs in a more general framework of cyclic alternating pattern (CAP), a sleep-instability measure considering reactibility as the main factor in sleep regulation.42, 43 KC associated with pathological events in sleep as epileptic seizures, sleep apnea and periodic limb movements has become an indicator of the cerebral component of these conditions.36, 44, 45, 46, 47, 48 Within the study of slow oscillations during NREM sleep cell-physiological basis of the pattern has also been explored.11
Although KC has become a common subject of physiology and sleep-medicine, a unified interpretation on its physiological role is hitherto missing. Interpretations are still lying in the ‘Procrustes bed’ qualifying KC as ‘arousal’ or ‘antiarousal’ pattern. Therefore, it is high time to develop a comprehensive review and interpretation on the subject.
During the following pages I will review the definitions, morphology and topography of KC, demonstrate the regular participation in NREM sleep, characterise the elicitability features of evoked KC, describe autonomic and motor concomitants, the relationship of KC with information processing during NREM sleep, the relationship of KC and deltas with NREM sleep, and with sleep cyclicity. Then the relationship of KC with synchronisation-type and desynchronisation-type micro-arousals and the ‘cyclic alternating pattern’ will be treated, with an emphasis on their distribution across the sleep cycles. Lastly the role of KC providing gating functions in idiopathic generalized epilepsies and different other sleep disorders will be described. A ‘theoretical epilogue’ is appended to show some system theoretical and regulational aspects.
Section snippets
Definitions, morphology (components) and topography of K-complex
‘Spontaneous KCs’ are not related to any known eliciting factor, and we use ‘evoked KC’ when it is related (in time) to a known sensory stimulus. Definition of the spontaneous KC is not easy since it shows a considerable variance in components and amplitudes. There is evidence for the similarity if not identity of the spontaneous and evoked KCs.3, 4, 49
Definitions and morphology of KCs are strongly related to the recording techniques used. The use of monopolar versus bipolar recordings,
K-complex as a regular component of NREM sleep EEG
KCs were studied mainly in stage 2 NREM sleep. The shortest interval found between two spontaneous KCs was 1–2 s. In the majority of cases, the single spontaneous KCs are separated by more than 3 s intervals,4 although spontaneous multiple KCs are common.
Studying 1565 KCs of four persons, Johnson and Karpan6 found the intervals between singular KCs between 30 and 70 s. In the histogram of intervals between K-alpha events MacFarlane et al.36 found a peak at 16–20 s. The frequency of KCs showed a
Influence of age on KC formation
Low-amplitude and long-duration KCs can be recognized by 5 months of age. The faster negative component appears between 3 and 5 yr and becomes more marked in adolescence.83 Kubicki et al.81 studied the frequency of KCs in different age groups (42 subjects, 18–77 yr). The group below 30 yr had a higher-, and the group over 50 a lower rate. Wauquier82 confirmed that aging was associated with decrease in KC-frequency with an important intraindividual variability. Investigating evoked KCs in ten
Stimulus characteristics, elicitability and features of evoked KC
Intensity of the stimulus increases KC-frequency.17 The slow stimulation-rate produces higher amplitude KCs than high.61, 66 KC was identified in 37% of the trials when a rare auditory stimulus was presented versus 17% when a frequent stimulus was presented.61 Also in the oddball paradigm KCs were elicited more often and were larger with rare-, than with frequent stimuli.28, 63 N300–350 has been reported to be larger to deviant than to standard stimuli.25, 58, 59
Kurella et al.,84 using paired
Cortical ‘window’ (microstate) for information processing during NREM sleep
Pál et al.88 has shown that the elicitation of a KC to a stimulus depends on the brain state preceding the stimulus presentation. The power of the fast frequency components (over 20 Hz) in ongoing EEG activity is higher when KC is elicitable.
Sallinen et al.31 found that before an evoked KC both the N350 component and the P210 were significantly higher to deviant stimuli compared to trials where KC could not be elicited.
As the Steriade school proved89, 90 a slow cortical oscillation takes place
Concomitants of KC: autonomic and muscle activity
There is an abundance of studies demonstrating autonomic and muscle activity conjoining KCs. Traditionally the KC associated phasic appearance of autonomic and muscle activity were considered as a crude activation pattern and, therefore, KC assumed to be an arousal pattern.4, 7, 17, 66, 91, 92 Pampiglione and Ackner93 showed that KC is related to transient vasoconstriction in the finger. Johnson and Karpan6 observed that spontaneous KC was associated with increased heart rate or increased
KC and information processing during NREM sleep
In the waking state after 250 ms, the late components of evoked potentials are considered as concomitants of cognitive information processing. A frequently emerging question is the extent to which the sleeper is aware of the external events or the extent of subconscious information processing during sleep.
By the use of acoustic evoked potentials (AEP) numerous studies have provided evidence for an ongoing stimulus-processing during sleep.15, 16, 21, 22, 24 Stimulus evaluation during sleep has
Relationship of KC and delta waves of NREM sleep
There are data that KC changes along the homeostatic process of slow wave activity in NREM sleep. More rapid sleep onset, reduced arousability, increased spindle-production and delta power—after sleep deprivation or sleep fragmentation caused relative sleep deprivation—correlate with increased KC-production.
Nicholas et al.62 induced sleep fragmentation with long auditory tones disturbing sleep. During the recovery night, the sleep-drive was increased, as indicated by increased amount of slow
Relationship with sleep cyclicity
In our early work, we also demonstrated the decay of KC density from evening to morning from cycle to cycle across the night sleep14 (Fig. 5). Kurella et al.84 studied the probability of eliciting KCs across the night sleep differentiating stage 2 periods according to their relation to the previous sleep stage: S2/1 when it was ‘near to stage 1’ and S2/3 if it was ‘near to stage 3’ and S2/R after REM sleep. They found that the probability of eliciting a KC is the highest during S2/3 and the
Relation of KCs with micro-arousals
The first systematic use of the term micro-arousal (MA) was defined as phasic desynchronisation or synchronisation type EEG events associated with automatic and/or motor arousal but not associated with behavioural awakening.113
We have seen that KCs are considered to be the building stones of slow wave sleep.13 They behave parallel with the NREM delta activity across the dynamic changes of sleep cyclicity in several aspects. However, KCs are elicitable by all modalities of sensory stimuli and
KCs, micro-arousals and the cyclic alternating pattern (CAP)
Another line of evidence for different type of arousals came from the discovery of the cyclic alternating pattern (CAP)42 representing a framework of arousal related phasic events appearing throughout the whole slow wave sleep showing differences only in morphology according to sleep stages. The CAP cycle consists of two phases: phase A and B. Related to the concept of synchronisation versus desynchronisation like phenomena, phase A is mostly identical with the MA events, while phase B is
Mechanism of KC and production of synchronization type micro-arousals
As we have seen KCs could represent a reaction to sensory input. The question is how, through which pathways and target-structures these impulses are realised in the brain. There are few works on the pathway of KC-evoking stimuli.
KCs were not recorded over the damaged hemisphere of patients with thalamic lesion causing loss of bilateral spindling and hemineglect, whereas they were elicited bilaterally by contra lateral and ipsilateral stimuli administered in an other case with spared spindling
Distribution of synchronization type and desynchronisation type micro-arousals across the cyclic sleep process
To understand the physiological function represented by the KC we should take into consideration that the KC is frequently not an isolated phenomenon but a part of a sequence of reactive EEG patterns, the micro-arousals. In other words, the KC phenomenon should be studied in the ‘garment’ of micro-arousals. The dynamics of microarousals is related to reactivity changes during the sleep process.
One of the factors determining the reactivity of the organism to stimulation is determined among other
Assumptions on the functions of micro-arousals especially those with KCs and slow waves during NREM sleep
Arousals and arousability in general, ensure the reversibility of sleep, without arousability sleep would be identical to coma. Arousals provide a connection of the sleeping subject with the environment maintaining the selection of relevant information and adapting the organism to the environment. In this dynamic perspective, the phasic events represent the arousal influences on one hand, and elements of information processing on the other. Therefore, arousal and information processing are the
KC and KC-related micro-arousal as a gateway for epileptic discharges in idiopathic generalized epilepsy
It was shown that the appearance of generalized spike-wave discharges (GSWD) is linked to a ‘critical level of vigilance’ between NREM sleep, wake state and REM sleep.46, 138, 139, 140, 141 Another interesting aspect is the strong link of GSWDs with phasic events representing arousals without awakening in superficial NREM sleep.46, 77, 142 These dynamic changes can be elicited and experimentally studied by sensory stimulation or forced awakenings.45, 77, 143 If sensory stimuli applied in NREM
Conclusion
Data on KC have been gathered from the first description 67 yr ago until the recent publications. It is clear that KC has a double-faced character. Being a periodically occurring (1.0–1.7/min) regular component of the NREM sleep EEG, KC is elicitable by different kinds of external sensory stimuli. KC is related to arousal without awakening not only by the sensory elicitability but also by the multi-fold autonomic and elementary behavioural concomitants. There are data supporting the assumption
Acknowledgements
I am grateful for the assistance of Anna SzŰcs PhD in improving the English text and Lalit Narula for editing.
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