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Biomedical subjects

Ian M Colrain

Publications and source records attributed to Ian M Colrain.

At least 19 recordsLinked to original sources

The impact of slow wave sleep proximity on evoked K-complex generation.

During human stage 2 non-rapid eye movement (NREM) sleep, spontaneous K-complexes are more likely to occur prior to transitions to stage 3 or stage 4 sleep (referred to as slow wave sleep or SWS) compared to transitions to REM sleep, suggesting that the K-complex may be the 'forerunner' of SWS. The present study investigated the impact of SWS or REM sleep proximity on the probability of evoking a K-complex (pKC) during stage 2 and on components of the NREM sleep averaged evoked potential. Ten subjects spent three nights in the laboratory. On either the second or third night tones were presented continuously during sleep. Evoked K-complexes and sleep-evoked potentials were assessed for the 10 min of stage 2 prior to SWS (SWS-10) or REM (REM-10) sleep episodes as well as for all of SWS. pKC did not differ between SWS-10 (0.88) and SWS (0.91) but was significantly larger in SWS-10 than REM-10 (0.63). Amplitude effects were seen for the P2, N350, P900 NREM sleep-evoked potential components but not for the K-complex related N550. In each case where amplitude effects were found, SWS-10 was larger than REM-10. No latency differences were seen between conditions for the earlier components (P2, N350) however, both N550 and P900 were significantly shorter during SWS-10 compared to REM-10. These results are consistent with previous spontaneous K-complex studies and are supportive of a relationship between the K-complex and delta activity. They also indicate that stage 2 may consist of a continuum of microstates between SWS and REM sleep that are indicative of different brain stem, diecephalic and cortical patterns of activation.

Acoustic Stimulation↗

The K-complex: a 7-decade history.

The K-complex was first described by Loomis et al 67 years ago in a paper that was one of a series of seminal studies of sleep conducted in Loomis' private laboratory. The study of the K-complex was almost immediately taken up by many notable figures in early electroencephalography research, such as Robert Schwab, Mary Brazier, and W. Gray Walter. More than 200 papers have been published in the years since these early studies, including major reviews in 1956 by Roth et al and in 1985 by Peter Halász. More recently, K-complex study has been taken up by event-related potentials researchers such as Ken Campbell and animal neurophysiologists such as Florin Amzica and Mircea Steriade. The present paper provides a historical and thematically based review of the K-complex literature and attempts to integrate the various theoretical positions and neurophysiologic data. Specifically, K-complexes are discussed in terms of their relationship to other electroencephalographic phenomena, their relationship to autonomic activation, their role in the study of information processing during sleep, and what is understood of their underlying neurophysiology.

Brain↗

Differentiating pathologic delta from healthy physiologic delta in patients with Alzheimer disease.

STUDY OBJECTIVE: In patients with Alzheimer disease, the electroencephalogram during wakefulness shows pathologic signs of abundant, diffuse, large-amplitude delta activity. The carryover of this abnormal delta activity into non-rapid eye movement sleep raises the question of whether the observed delta electroencephalographic activity during sleep in Alzheimer disease in any way reflects normal physiologic delta activity slow-wave sleep. The objective of the study was to compare patients with Alzheimer disease with age-matched controls using an experimentally controlled procedure that can test the capacity of the nervous system to generate physiologic delta-frequency responses during sleep. SETTING: Research sleep laboratory. PARTICIPANTS: Seven ambulatory patients with Alzheimer disease (mean age = 70.0 +/- 5.77 years) meeting the National Institute of Neurological and Communicative Diseases and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease and 8 controls (mean age = 69.25 +/- 4.95 years), underwent at least 1 night of evoked-potential recordings. MEASUREMENT AND RESULTS: Data were collected during stage 2 sleep. Responses to stimuli were classified based on whether they produced a K-complex. Averages of K-complex responses were calculated, latencies and amplitudes of components evaluated, and K-complex incidence was determined. Relative to controls, subjects with Alzheimer disease produced significantly fewer evoked K-complexes (P < .001) and had substantially smaller N550 amplitudes than controls (P < .05). A lower probability of eliciting a K-complex correlated with greater dementia severity, as measured by the Mini Mental State Examination and Dementia Rating Scale. CONCLUSIONS: Despite observed increases in pathologic delta-frequency electroencephalographic activity, patients with Alzheimer disease have an impaired capacity to generate normal physiologic delta responses during non-rapid eye movement sleep.

Acoustic Stimulation↗

Genetic and environmental influences in sleep-disordered breathing in older male twins.

STUDY OBJECTIVES: To estimate the extent to which genetic factors contribute to the variation in several indices of sleep-disordered breathing in elderly male twins. DESIGN AND SETTING: A biometric genetic study based on data from unattended Edentrace recordings in a sample of elderly male twins. PARTICIPANTS: 122 World War II male veteran twin pairs, including 68 monozygotic pairs aged 78.9 (+/- 2.7) years and 54 dizygotic pairs aged 78.4 (+/- 2.4) years. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The average (+/- SD) respiratory disturbance index for this sample was 17.2 +/- 14.5, the average (+/- SD) oxygen desaturation index was 18.8 +/- 16.4, and the average (+/- SD) minimum SaO2 level was 79.6 +/- 8.1%. Intraclass twin-pair correlations for log-transformed respiratory disturbance index were 0.59 in monozygotic pairs and 0.36 in dizygotic pairs. For oxygen desaturation index, intraclass correlations were 0.44 in monozygotic pairs and 0.24 in dizygotic pairs. For minimum SaO2, intraclass correlations were 0.38 and 0.11, respectively. Maximum likelihood estimates of heritability with associated 95% confidence intervals were 37% [22%, 52%] for respiratory disturbance index, 36% [19%, 53%] for oxygen desaturation index, and 10% [0%, 30%] for minimum SaO2. Adjustments of sleep-disordered breathing measures for age, body mass index, and waist and neck circumference had minimal effect on estimates of heritability. CONCLUSIONS: The present data indicate that sleep-disordered breathing, even in old age, is determined, in part, by genetic factors.

Aged↗

P300 from inspiratory occlusion reflects orienting but not startle.

Sudden onset inspiratory occlusion stimuli elicit large amplitude P300 components and also startle blinks. The primary purpose of this study was to assess the influence of the startle reflex on the respiratory related P300. A secondary purpose was to assess changes in P300 scalp topography as a function of stimulus familiarity. Young adults (n=12) were exposed to 200 inspiratory occlusion stimuli, and EEG was recorded from 29 A1/A2 referenced sites. Data from the occlusions were divided into four consecutive blocks of 50 trials to assess blink and P300 habituation effects. Results showed that 40% of the occlusion stimuli elicited a blink response, and that blink amplitude showed significant habituation across the experimental session. Change in P300 amplitude across the experimental session varied according to scalp site. At central and parietal locations, P300 amplitude showed an initial decrease but then remained stable. Frontally, P300 amplitude decreased over each of the four trial blocks. P300 scalp topography showed a classic centro-parietal maximum, however, a more frontally orientated scalp focus was seen for the first trial block. P300 was not significantly different when derived from averages of responses containing and not containing blinks. These data indicate that the previously studied centro-parietal P300 is not related to a startle reflex. However, when occlusions are first presented, a scalp topography similar to that previously noted for novel stimuli is observed.

Adolescent↗

Evoked K-complex generation: the impact of sleep spindles and age.

OBJECTIVE: It has been proposed that spindles and spontaneous K-complexes reflect two sides of a coin, with the spindle reflecting an inhibitory microstate and the K-complex reflecting an excitatory or aroused microstate [Physiol Behav 1993;54(4):795]. This hypothesis predicts that the presence of a sleep spindle at the time of stimulus presentation would decrease the likelihood of a K-complex being elicited by that stimulus. The present study sought to test this hypothesis in young and elderly subjects. METHODS: Ten young and 7 elderly adults who were neurologically healthy and free from medications spent one night in the sleep laboratory. EEG was recorded from 6 gold plate electrodes (Fz, FCz, Cz, CPz, Pz and O2) referenced to A1+A2. Tone clicks (1000 Hz) at 80 dB above measured awake detection thresholds were presented binaurally either during a spindle (SP+) or in the absence of a spindle (SP-). This was achieved by viewing a central EEG channel filtered to pass only the frequencies between 12 and 14 Hz. Trials were further classified based on whether (KC+) or not (KC-) they produced a K-complex. K-Complex probability and the amplitude and latency of the N550 component of the averaged evoked potential for KC+ trials were assessed using a two-way analysis of variance with main effects of age and spindle presence/absence. RESULTS: There were significant reductions in K-complex probability and N550 amplitude and a significant increase in N550 latency, as a function of age. However, no variable displayed a significant effect of spindle presence/absence, or an age x spindle interaction effect. CONCLUSIONS: The data failed to support the hypothesis that sleep spindles are antagonistic to the production of K-complexes, both in terms of the likelihood of K-complexes being elicited or in their amplitude when elicited (N550). The absence of spindle effects on K-complex generation argues against them being two sides of a coin and supports the notion of K-complexes having an extra-thalamic or non-specific generation mechanism.

Acoustic Stimulation↗

A review of the evidence for P2 being an independent component process: age, sleep and modality.

This article reviews the event-related potential (ERP) literature in relation to the P2 waveform of the human auditory evoked potential. Within the auditory evoked potential, a positive deflection at approximately 150-250 ms is a ubiquitous feature. Unlike other cognitive components such as N1 or the P300, remarkably little has been done to investigate the underlying neurological correlates or significance of this waveform. Indeed until recently, many researchers considered it to be an intrinsic part of the 'vertex potential' complex, involving it and the earlier N1. This review seeks to describe the evidence supportive of P2 being the result of independent processes and highlights several features, such as its persistence from wakefulness into sleep, the general consensus that unlike most other EEG phenomena it increases with age, and the fact that it can be generated using respiratory stimuli.

Adult↗

The impact of smoking cessation on objective and subjective markers of sleep: review, synthesis, and recommendations.

Sleep disturbance is commonly reported as a prominent subjective symptom by quitting smokers. However, little research on this issue has used objective measures of sleep quality. Previous research has relied mainly on retrospective report of sleep disturbance, with few studies investigating sleep during the initial period after quitting tobacco use. Studies that have used objective measurements suggest that sleep fragmentation is a common occurrence during the withdrawal period. In sleep medicine, sleep disturbance is viewed as a consequence of frequent arousals and is now considered to have particularly deleterious daytime consequences, including sleepiness and dysphoric mood. Recent work also indicates that such awakenings affect the cardiovascular system by providing repetitive bursts of sympathetic nervous system activation, possibly contributing to elevated levels of cardiovascular and cerebrovascular morbidity. Pharmacological treatments designed to facilitate smoking cessation are ineffective for sustained abstinence in many smokers, which may be related to sleep disturbance. Indeed, preliminary evidence suggests that the administration of nicotine replacement therapy (NRT) or bupropion can result in disrupted sleep, particularly in women. However, to better understand the role that nicotine withdrawal and bupropion or NRT treatment, independently and in combination, might play in sleep disturbance, it is necessary to develop a better understanding of the nature of the sleep disturbance than can be provided by self-report. This is particularly important for the development of treatment approaches targeted to ameliorate sleep disruption as part of an overall smoking cessation strategy. The present review seeks to report the current state of knowledge based on extant findings and argues for the need to conduct more detailed polysomnographic investigations of the potentially vicious cycle of smoking cessation leading to sleep disturbances that may prove iatrogenic to sustained cessation.

Administration, Cutaneous↗

Sleep and respiratory stimulus specific dampening of cortical responsiveness in OSAS.

The application of inspiratory occlusion stimuli produces cortical responses called respiratory-related evoked potentials (RREPs). During wakefulness the RREP waveform consists of early P1 and Nf components, an N1 and a P300. During non-REM sleep the predominant component is an N550, best seen in the averages of elicited K-complexes. Obstructive sleep apnea syndrome (OSAS) patients have been previously shown to have a normal wake RREP but to have a reduced amplitude N550 and a smaller proportion of elicited K-complexes than controls. The present study tested the hypothesis that this reflects a sleep-specific dampening peculiar to inspiratory effort-related stimuli, by assessing both respiratory and auditory evoked potentials (AEPs) during wakefulness and non-REM sleep in OSAS patients and controls. Auditory tones were presented in an oddball sequence during wakefulness and as a monotonous series during stage 2 sleep. Inspiratory occlusions, delivered for 500 msec via an nCPAP mask were also presented during wakefulness and stage 2 sleep, every three to five breaths. Data were collected from ten OSAS patients and ten controls. There were no significant differences in the amplitudes of the auditory N1 and P3 or the respiratory P1, Nf, N1 or P3 components during wakefulness. The amplitude of the auditory N550 and the proportion of elicited K-complexes did not differ between groups for auditory stimuli presented during stage 2 sleep. The respiratory N550 and K-complex elicitation rate were both significantly reduced in the OSAS group, despite there being no differences in the mask occlusion pressure response to the occlusion. The results confirm a blunted cortical response to inspiratory occlusions that is specific to sleep. The absence of significant group differences in the responses to auditory stimuli highlight that the sleep-related differences seen in OSAS patients are specific to the processing of inspiratory effort related stimuli.

Acoustic Stimulation↗

The effects of hormone replacement therapy on sleep-disordered breathing in postmenopausal women: a pilot study.

STUDY OBJECTIVES: To evaluate the impact of estrogen and estrogen plus progesterone hormone-replacement therapy (HRT) on mild-to-moderate sleep-disordered breathing (SDB) in postmenopausal women. DESIGN AND SETTING: Within-subjects, progesterone placebo-controlled prospective HRT trial in a clinical laboratory. PARTICIPANTS: Six postmenopausal women, diagnosed with mild-moderate SDB. INTERVENTION: Transdermal estradiol and oral micronized progesterone. MEASUREMENTS AND RESULTS: Subjects underwent polysomnography (PSG) on four occasions: a screening/adaptation night; a baseline night on no HRT; and two nights on HRT: one night after 7 to 12 days on estrogen plus placebo followed by a second night after 7-13 days on estrogen plus progesterone. The PSG was performed with a Sandman computerized PSG system using a standard clinical montage. Modified sleep diaries were used in the baseline week and throughout the study period. Mood was measured with the 20-item version of the Positive and Negalive Affect Schedule (PANAS). Estrogen monotherapy was associated with a significant reduction in the overall apnea-hypopnea index (AHI) (from a mean of 22.7 events per hour at baseline to a mean of 12.2 events per hour), but the AHI reduction on estradiol plus progesterone relative to baseline was not statistically significant (AHI=16.2 events per hour). Similar results were found for the percentages of total sleep time and of total non-rapid eye movement sleep time with oxygen saturation less than 90%. Estrogen, neither alone nor in combination with progesterone, significantly altered PSG- or diary-based measures of total sleep time, time to sleep onset, or time awake after sleep onset. CONCLUSIONS: While the data are preliminary and based on a small number of subjects, estrogen appeared to have a substantial beneficial effect on measures of SDB in postmenopausal women. Overall, no additional benefit was seen with the addition of progesterone. In fact, progesterone attenuated the beneficial effects of estrogen in 4 out of the 6 participants.

Administration, Oral↗

Evidence of a sleep-specific blunted cortical response to inspiratory occlusions in mild obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) patients have elevated non-rapid eye movement (REM) sleep arousal thresholds to inspiratory loading. To test the hypothesis that this is due to sleep-specific dampening of cortical responses to inspiratory effort, respiratory-related evoked potentials (RREPs) were evaluated in six mild OSAS patients and six age- and body mass index-matched controls during wakefulness and Stage 2 non-REM sleep. Electroencephalogram was recorded from six scalp sites (Fz, FCz, Cz, CPz, Pz, and O(2)). Electrooculogram, electromyogram, and mask pressure signals were also recorded. During sleep, pharyngeal pressure was recorded using a Millar pressure catheter placed 2 cm below the glottis. The RREP waveform was broadly similar in the two groups during wakefulness, but was markedly different during Stage 2 non-REM sleep. During wakefulness, only the N1 component showed reduced amplitude in the OSAS group. During sleep, the occlusion stimulus elicited fewer K-complexes in the OSAS patients. In addition, the N550 component in the average of K-complex responses was smaller in amplitude in the OSAS group. The data suggest that patients with mild OSAS have a "blunted" response to the respiratory occlusion stimulus. This appears not to be related to compromised mechanoreceptor function, as the RREP was normal in the patients when they were awake.

Adult↗

P3-specific amplitude reductions to respiratory and auditory stimuli in subjects with asthma.

The respiratory-related evoked potential (RREP) is the electroencephalographic response to brief inspiratory occlusion. The P3 component of the response reflects the active cognitive processing of stimulus information. This study investigated the RREP in 16 subjects with asthma and 16 control subjects. In addition, auditory-evoked potentials were recorded using an oddball paradigm in both groups and were compared with the RREP results. Perceptual sensitivity was assessed using a load magnitude estimation task, whereby subjects estimated the magnitude of four added resistive loads using a modified Borg scale. For RREP assessment, inspiratory occlusions were presented for 200 milliseconds. For auditory-evoked potential assessment, 1,000- and 2,000-Hz pure tones were presented at 60 dB for 100 milliseconds, with the 2,000-Hz tone presented with 20% probability and identified as a target stimulus. Scalp electroencephalographic activity was measured from 29 channels. Resistive load intensity was linearly related to magnitude estimation in both subjects with asthma (r2 = 0.96) and control (r2 = 0.99) subjects. Results showed that both the respiratory and auditory P3 components were markedly reduced in the group with asthma compared with the control group. Other components were similar between the groups. These results suggest an intrinsic reduction in P3 amplitude for patients with asthma, which may relate to differences in processing perceptual information.

Adolescent↗

Event-related potential measures of the inhibition of information processing: II. The sleep onset period.

The loss of consciousness during the sleep onset period is associated with dramatic changes in information processing. Human event-related potentials (ERPs) reflect these changes. Short- and mid-latency ERPs are only minimally affected by sleep onset. On the other hand, long-latency ERPs are very much affected. A negative wave, N1, peaking at approximately 100 ms gradually decreases in amplitude until it reaches baseline level during definitive stage 2 sleep. The changes in N1 are especially apparent when the subject no longer signals awareness of the external stimulus or when stage 1 is dominated by theta activity in the EEG. The positive peaks, P1 and P2, peaking at approximately 50 and 180 ms, respectively, may appear to increase in amplitude (i.e. also be less negative). A long-lasting processing negativity (PN) may overlap and summate with these peaks during the waking state. During sleep onset, the PN dissipates, thus explaining the apparent positive baseline shift in the ERP waveform. In an oddball task, when an alert and awake subject detects a rare, relevant stimulus, a large positive wave, P300, maximum over parietal areas of the scalp, is observed. This P300 is, however, widely dispersed and can be observed over frontal areas of the scalp. When the subject no longer signals detection of this target stimulus, P300 can no longer be recorded. During stage 1, the parietal P300 remains large, providing the subject overtly detects the target. The amplitude of the frontal aspect of P300 is much reduced as response times slow. This may reflect deactivation of the frontal lobes during the sleep onset period. The infrequent change of an otherwise rapidly presented homogenous train of stimuli is associated with another long-lasting negativity, the mismatch negativity (MMN). The MMN also decreases in amplitude during the sleep onset period, reaching baseline level during definitive sleep. The vertex sharp wave (VSW) becomes apparent during the sleep onset period. Associated with the VSW is a late negative ERP, sometimes called the sleep N2 or the N350, peaking between 300 and 350 ms. It is unique to the sleep onset and sleep periods, becoming very large during stage 1-theta or when the subject no longer shows signs of awareness of the external stimulus.

Animals↗

Evoked potential components unique to non-REM sleep: relationship to evoked K-complexes and vertex sharp waves.

Following the loss of wakeful consciousness, the averaging of responses to stimuli produce evoked potential waveforms with prominent components either unique to or greatly enhanced by non-REM sleep. In the sleep onset periods (stage 1) these are the P2 and N350. Following the establishment of stable sleep (stage 2 and SWS), the N550 and P900 are also prominent. Investigation of the EEG associated with individual responses indicates that a good proportion of stimuli elicit, K-complexes or vertex sharp waves (VSWs) and occasionally will elicit both. Recent work has indicated that the N550 in the averaged response is due to the presence of K-complexes and that the N350 is at least largely due to the presence of VSWs. The large size of these grapho-elements indicates that they are probably produced by a synchronized discharge of multiple neural units. Both are readily observed in the absence of external stimulation and occur as normal components of sleep, indeed the K-complex is used as one of the identifying features of the onset of stable non-REM sleep. The present review details the investigation of these features and their associated evoked potential components, in terms of stimulus features, brain states associated with their production, their scalp topography, and changes as a function of age.

Animals↗

The effects of normal aging on sleep spindle and K-complex production.

OBJECTIVES: Despite a relatively large body of literature describing the characteristics of sleep spindles and K-complexes in young adults, relatively little research has been conducted in older individuals. The general consensus from the few studies that have addressed this issue is that there is a progressive decrease in the number of spindles and K-complexes with age, although there is large intra-individual variation. Whether or not these changes are an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently from those of disease. METHODS: Fourteen young adults (mean age=21.4+/-2.5 years) and 20 older adults (mean age=75.5+/-6.3 years) participated in the study. All subjects were neurologically and medically healthy and were not taking any medications with a known effect on the central nervous system or sleep. For each subject, a number of characteristics were determined including the number, density (SS/min), amplitude and frequency of all spindles as well as the number and density of K-complexes (KC/min). RESULTS: Spindle number, density and duration as well as K-complex number and density were all significantly lower in the elderly compared to the young adults. The EEG frequency within the spindles was significantly higher in the elderly, although the absolute difference was less than 0.5 Hz. Multiple regression analysis indicated that spindle duration and K-complex density were able to predict over 90% of the variance in age. CONCLUSIONS: The age-related decrease in sleep spindle and K-complex density is consistent with previous reports and may be interpreted as an age-related alteration of thalamocortical regulatory mechanisms.

Adult↗

The effect of stimulus probability on P3 in the respiratory-related evoked potential.

The present study investigated the effect of target stimulus probability on the P3 component of the respiratory-related evoked potential (RREP). A single respiratory stimulus paradigm was employed where normal breaths served as standard stimuli and occluded breaths presented at various probability levels served as target stimuli. EEG was recorded from 29 channels in young adults in two conditions. In Condition 1, occlusions were presented at target probabilities of 0.5, 0.33, 0.25, 0.2, 0.1, and 0.05, that is, every 2nd, 3rd, 4th, 5th, 10th, and 20th breath. Order of target probability presentation varied randomly. Condition 2 used the same target probabilities, but held breathing rate constant by using a paced respiration task. Results indicated that P3 amplitude was significantly affected by stimulus probability, such that the component showed an inverse relationship with probability. This effect was similar between conditions. However, P3 amplitude reduced and latency increased when the secondary task of paced respiration was introduced. These data suggest that models developed to describe the effect of stimulus probability on the amplitude of visual and auditory P3 components are applicable to the respiratory somatosensory modality.

Adult↗