Kate E. Crowley

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.

An examination of evoked K‐complex amplitude and frequency of occurrence in the elderly

The elderly consistently display lower levels of slow wave sleep (SWS), primarily because of the small amplitude of their delta activity. Given that delta electroencephalogram (EEG) and K‐complexes are thought to be generated by the same mechanisms, it was hypothesized that K‐complex amplitude and rate of production would be lower in the elderly. K‐complex amplitude was assessed by averaging K‐complex responses to auditory stimuli, and measuring the amplitude of the N550 component of the averaged evoked response. Ten young (five males and five females; mean age 23.10 ± 5.36 years) and 10 elderly adults (six males and four females; mean age=75.60 ± 4.48 years) who were neurologically healthy and free from medication spent two non‐consecutive nights in the sleep laboratory. EEG was recorded from six gold plate electrodes (Fz, Fcz, Cz, Cpz, Pz and O2) referenced to A1 + A2. Tone clicks (1000 Hz), of varying intensity from 70 to 100 decibels above measured awake detection threshold, were presented binaurally during stage 2 sleep. Responses were classified according to whether they produced: a K‐complex, a vertex sharp wave (VSW), both of these responses or neither response. They were then averaged separately for each response type. The elderly showed a substantially smaller N350 (averaged VSWs) and N550 amplitudes compared with the young subjects. The elderly also showed an augmented but delayed P2 component, followed by a long‐lasting positive EEG shift. The smaller amplitude of the averaged K‐complex N550 component is consistent with lower delta amplitudes previously reported in the elderly and with the hypothesis that K‐complexes and delta activity share the same generator mechanisms. The enhanced P2 component and the long‐lasting positive deflection in the EEG in the elderly indicate the existence of age differences other than smaller EEG amplitude.

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.

Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan

Aging is associated with many changes in sleep, with one of the most prominent being a reduction in slow wave sleep. Traditional measures of this phenomenon rely on spontaneous activity and typically confound the incidence and amplitude of delta waves. The measurement of evoked K-complexes during sleep, enable separate assessment of incidence and amplitude taken from the averaged K-complex waveform. The present study describes data from 70 normal healthy men and women aged between 19 and 78 years. K-Complexes were evoked using short auditory tones and recorded from a midline array of scalp sites. Significant reductions with age were seen in the amplitude of the N550 component of the averaged waveform, which represents the amplitude of the K-complex, with linear regression analysis indicating approximately 50% of the variance was due to age. Smaller, yet still significant reductions were seen in the ability to elicit K-complexes. The data highlight the utility of evoked K-complexes as a sensitive marker of brain aging in men and women.

The Impact of Alcoholism on Sleep Evoked Δ Frequency Responses

BACKGROUND K-complexes (KCs) are evoked delta frequency electroencephalogram (EEG) responses during sleep that occur when large numbers of healthy cortical cells burst fire in a synchronized manner. The KC amplitude and incidence are sensitive measures of normal healthy brain aging. Given the known neurodegenerative consequences of alcohol abuse it was hypothesized that alcoholism would be associated with further KC amplitude and incidence reductions. METHODS Eighty-four subjects (42 alcoholics) screened for medical, psychiatric, and sleep problems participated. The protocol involved the presentation of auditory stimuli during stage 2 sleep throughout a night in the laboratory. The KCs were identified and averaged, to enable measurement of the P2, N550, and P900 peaks. RESULTS Compared with control subjects, alcoholic men and women had lower KC incidence (p < .001) and P2 (p < .001), N550 (p < .05), and P900 (p < .05) amplitudes. There was a significant diagnosis x site interaction (p < .001), indicating the group difference was largest at frontal sites. Longer sobriety correlated with increased N550 amplitude (p < .01). CONCLUSIONS The KC incidence and amplitude were negatively impacted in alcoholic men and women with exacerbation of the normal aging effects, particularly over frontal scalp regions. The observed relationship between improvements in KC measures and increased time of abstinence suggests that these measures might provide a useful marker of brain recovery with continued abstinence from alcohol.

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.

The effect of blinks and saccadic eye movements on visual reaction times

Vision is suppressed during blinks and saccadic eye movements. We hypothesized that visual reaction times (RTs) in a vigilance test would be significantly increased when a blink or a saccade happened to coincide with the stimulus onset. Thirty healthy volunteers each performed a visual RT test for 15 min while their eye and eyelid movements were monitored by a system of infrared reflectance oculography. RTs increased significantly, many by more than 200 msec, when a blink occurred between 75 msec before and up to 150 msec after the stimulus onset. A similar result was observed with saccades that started 75 to 150 msec after the stimulus. Vision or attention was evidently inhibited before each blink and for longer than the saccades lasted. We suggest that visual suppression is involved in this process, which could explain some of the normal variability in RTs over periods of seconds that has not been adequately explained before.

Self-reported sleep patterns and daytime sleepiness in the neurologically healthy aged.

Many population-based surveys have reported great changes way in which health status has been conceptualised. The field of sleep disorders research has to a large extent approached in subjective sleep patterns with increasing age. Most studies have shown between 25 and 50% of the elderly complain about the problem of defining normal by studying individuals as free from disease as possible. However, given that as people age, the quality and/or quantity of their sleep; including difficulty initiating and maintaining sleep, disturbed or light sleep, they are more likely to suffer from one or more chronic health conditions (Dywan et al. 1992), using only the pristinely healthy frequent nocturnal awakenings and an increase in excessive daytime sleepiness (Flamer 1996; Bliwise et al. 1992; Vitiello provides a distorted view of normal (i.e. usual) aging. More recently, there has been some recognition that not all health et al. 1993; Bliwise 1993). There is, however, some controversy as to whether the observed poor sleep and increased daytime problems will have the same effect on sleep (Prinz et al. 1990). For example, aspects of an individual’s health that may have sleepiness represent a function of aging per se, or the contribution of other age-related diseases and chronic health an impact on the integrity of the central nervous system can be differentiated from those that do not. Given this logic, the conditions prevalent in the elderly. A number of recent studies have shown that when mental and physical health factors were ideal group to study would be a group of neurologically healthy older adults. Such a group would thus be normal in terms of controlled for, the incidence and prevalence of sleep complaints in the elderly are considerably less than previously thought central nervous system functioning, even though some of them would be experiencing other age-related health problems. (Ford and Kamerow 1989), and that daytime sleepiness was no greater and perhaps even less than that seen in young adults Recently, we evaluated the self-reported sleeping patterns and daytime sleepiness in a group of 30 neurologically healthy (Valencia-Flores et al. 1993; Reynolds et al. 1991). One explanation for the variation in age-related changes in elderly subjects (mean age 75.1±5.85) and 30 healthy young adults (mean age 19.7±3.34). Based on an extensive medical self-reported sleep in normal aging could be because of the

Chapter 11 Evoked potentials during non-REM sleep: utility and functional significance

Publisher Summary This chapter discusses how both auditory- and respiratory-evoked potentials change with non-REM sleep, with particular focus on two components: the N350 and N550. Very early in the history of sleep research, it became apparent that evoked Electroencephalography (EEG) responses could be elicited during non-rapid eye movement (REM) sleep. The first evoked response observed was the K-complex. This was seen in response to a tone played during an afternoon nap when the subject was in what we now call “stage-2 sleep.” Reasons to evaluate event-related potentials (ERPs) during sleep are many and varied. A substantial body of work has focused on the sleep onset period, with the goal of characterizing the loss of wakeful consciousness. Yet other studies have used ERPs during sleep as a way to evaluate the impact of aging or of different pathologies on the sleeping brain. Regardless of the motivation, the use of averaged ERP methods to evaluate sleep EEG is a departure from the standard observational mode of sleep research and provides the opportunity to probe the sleeping nervous system and evaluate the responses under a high level of experimental control.