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Biomedical subjects

J Harsh

Publications and source records attributed to J Harsh.

At least 19 recordsLinked to original sources

Effect of sleep deprivation on NREM sleep ERPs and related activity at sleep onset.

This research assessed the impact of one night of sleep deprivation on the amplitudes of NREM-sleep event-related potentials (NREM ERPs) and on the frequency of occurrence of related electroencephalogram activity including sleep spindles, arousals, K-complexes, and vertex sharp waves (VSWs). The NREM ERPs identified included P220, N350, P450, N550 and P900. During a pre-deprivation night, ten subjects took two 20-min naps separated by a 20-min break at their normal bedtime. Brief tones were presented at three intensity levels (60, 75 and 90 dB) with a 5-s interstimulus interval. Following these naps, subjects were kept awake until their normal bedtime the following day. At that time, they repeated the two-nap procedure. The ERPs obtained for each tone and wake/sleep state for pre- and post-deprivation conditions were analyzed using repeated measures statistical procedures. As anticipated, NREM ERP amplitudes recorded both pre- and post-deprivation increased with tone intensity and with approaching sleep. Also, sleep deprivation was associated with more rapid sleep onset, reduced arousability, and greater spindle production. While sleep deprivation had no effect on the amplitude of P220. Post-deprivation amplitudes of N350, N550 and P900 were greater, especially following the 90-dB tone. There was a corresponding increase in VSWs and K-complexes. These findings are inconsistent with the view that NREM ERPs reflect arousal. The underlying mechanism(s) may facilitate initiation and maintenance of sleep.

Adult↗

Low cerebrospinal fluid hypocretin levels found in familial narcolepsy.

OBJECTIVE: This report describes abnormal hypocretin neurotransmission in a case of familial narcolepsy. BACKGROUND: Narcolepsy is a chronic, often-disabling central nervous system disorder characterized by excessive daytime sleepiness and abnormal rapid eye movement (REM) sleep features including cataplexy, a loss of muscle tone triggered by emotion. The cause of human narcolepsy is unknown. Several familial cases have been described, but most cases are sporadic (95%). An abnormality of hypocretin neurotransmission has been found in a majority of sporadic cases. METHODS: Hypocretin-1 levels were measured in the cerebrospinal fluid of the narcoleptic proband of a family with several affected members. RESULTS: The proband was found to have a hypocretin-1 deficiency. CONCLUSION: Abnormal hypocretin neurotransmission is found in familial, as well as sporadic, narcolepsy.

Journal Article↗

P300 and sleep-related positive waveforms (P220, P450, and P900) have different determinants.

Stimulus factors known to influence the amplitude of the well known endogenous event-related potential (ERP) component P300 were manipulated to determine whether they have the same, or a different, influence on the amplitude of positivities of the sleep ERPs identified as P220, P450, and P900. Behavioral responsiveness and ERPs were recorded as subjects moved from wakefulness to sleep while performing an oddball task. The task consisted of sequential presentation of target and non-target tone stimuli with instructions to respond to targets with a finger--lift response. The probability of the target and non-target stimuli was varied (0.2/0.8, 0.5/.05 and 0.8/0.2) across three test conditions. While subjects were awake, P300 was maximal parietally with amplitude inversely related to the relative probability of the evoking stimulus and directly related to its task relevance. Positive waveforms (P220, P450, P900) recorded in sleep were largest at frontal and central recording sites. P220 and P900 amplitudes were inversely related to stimulus probability. P220 was smaller following target relative to non-target stimuli. Processes underlying P220, P450, and P900 sleep-related waveforms are different from those underlying the P300 component seen in alert wakefulness. The sleep positivities may be state-related waveforms subject to modulation by psychological processes.

Acoustic Stimulation↗

Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy.

Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of two 9-week, double-blind, placebo-controlled, multicenter, clinical trials of modafinil were enrolled in two 40-week, open-label, extension studies. A flexible-dose regimen (i.e. 200, 300, or 400 mg daily) was followed in one study. In the second study, patients received 200 mg/day for 1 week, followed by 400 mg/day for 1 week. Investigators then prescribed either 200- or 400-mg doses for the duration of the study. Efficacy was evaluated using Clinical Global Impression of Change (CGI-C) scores, the Epworth Sleepiness Scale (ESS), and the 36-item Medical Outcomes Study health survey (SF-36). Adverse events were recorded. Data from the two studies were combined.Results: The majority of patients ( approximately 75%) received 400 mg of modafinil daily. Disease severity improved in >80% of patients throughout the 40-week study. At weeks 2, 8, 24, and 40, disease severity was 'much improved' or 'very much improved' in 49, 58, 59, and 58% of patients, respectively. The mean (+/-SEM) ESS score improved significantly from 16.5+/-0.2 at open-label baseline to 12.4+/-0.2 at week 2 and remained at that level through week 40 (P<0.001). Quality of life scores at weeks 4, 8, 24, and 40 were significantly improved versus open-label baseline scores for six of the eight SF-36 domains (P<0.001). The most common treatment-related adverse events were headache (13%), nervousness (8%), and nausea (5%). Most adverse events were mild to moderate in nature. A total of 341 patients (71%) completed the studies. Forty-three patients (9.0%) discontinued treatment because of adverse events.Conclusions: Modafinil is effective for the long-term treatment of EDS associated with narcolepsy and significantly improves perceptions of general health. Modafinil is well tolerated, with no evidence of tolerance developing during 40 weeks of treatment.

Journal Article↗

Night-time sleep and daytime sleepiness in narcolepsy.

This report describes night-time sleep and daytime sleepiness in a large (N=530) sample of patients meeting the International Classification of Sleep Disorders criteria for diagnosis of narcolepsy. Sleep data were obtained from polysomnographic recordings on two consecutive nights. Sleepiness was assessed using the Multiple Sleep Latency Test, the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale. Analysis revealed that sleep was mild to moderately disturbed on both recording nights. A first-night effect was suggested by decreased REM latency and increased percentage REM and slow-wave sleep on the second night. Sleepiness and sleep disturbance varied across patient subgroups created based on patient ethnicity and on the presence/absence of cataplexy, sleep apnoea, and periodic limb movements. Covariation of sleep and sleepiness measures across patients was significant but weak. Strong association was found between subgroup means of sleep and sleep disturbance measures. The findings reported here show that sleepiness and sleep disturbance vary across patient subgroups and that sleep disturbance is related to, although unable to account, for the pathological sleepiness of narcolepsy.

Adolescent↗

Information processing and coping style during the wake/sleep transition.

Information processing of meaningful events (subject's own name, neutral name and tones) was studied during the transition from wakefulness to sleep in two groups of subjects with opposing information processing styles, Monitors and Blunters. In two experimental sets, subjects were instructed to execute a fingerlift response to a predetermined stimulus type. Subject's own name produced the greatest number of K-complexes and arousals relative to other name and tones. A task relevance effect was found for arousals but not for K-complexes. The overall P3 amplitude was larger for Monitors than for Blunters, whereas Blunters showed a larger N350 to target stimuli than Monitors. The findings suggest that higher level processing continues during light sleep and that N350 may reflect a process related to sleep maintenance.

Adaptation, Psychological↗

ERP and behavioral changes during the wake/sleep transition.

Event-related potentials (ERPs) following infrequent and frequent stimuli were studied as subjects moved from wakefulness to sleep. Subjects were instructed to respond to the infrequent "target" stimuli (attend condition) or to ignore the stimuli (ignore condition). Parietal P300, prominent following target ERPs in wakefulness under the attend condition, disappeared in association with reduced behavioral responsiveness and emergence of a central negativity (N350). The N350 and preceding and following positivities (P220 and P450) became the dominant feature of both target and nontarget ERPs under both attend and ignore conditions. The P220-N350-P450 complex was larger and peak latencies were shorter under the attend condition. Peak amplitudes tended to be larger following targets, especially under the attend condition. The findings suggest that, although the processes underlying P300 are less likely to be engaged, processing of stimulus deviance and task relevance continues in sleepiness and sleep, and is reflected by variance in N350 and related activity.

Adolescent↗

An examination of leadership style and its relevance to shift work in an organizational setting.

Results form the present research suggest that leadership style may be different for day and night and shifts, the relationship between leadership and job satisfaction is different for night and day shift employees, and the relationship between leadership and performance appraisal is not different for day and night shift workers. Implications for shift workers and further research questions are discussed.

Adult↗

Temperature, time-of-night of testing, and responsiveness to stimuli presented while sleeping.

The present study examined how time-of-night of testing and body temperature related to responsiveness to stimuli presented in sleep. Nine males slept for two nonconsecutive nights in the sleep laboratory. On Night 1, tympanic temperature was assessed at 30-min intervals. On Night 2, responsiveness was assessed with an incremental series of tones (5dB steps) presented in sleep stages 2, 3/4, and REM throughout the night (0030-0800 h). Subjects were instructed and given practice prior to sleep to make a microswitch closure to the tones. Results showed a curvilinear pattern of responsiveness across the night in that the intensity of tones required for a response increased until about 0530 h, then decreased thereafter. This pattern of responsiveness was positively related to the circadian rhythm of body temperature. A close correspondence was also found between the temperature trough and the performance trough (both occurred at about 0530 h). A greater emphasis on circadian factors may help understand previously reported but contradictory findings. The present results also suggest that measures of responsiveness follow a circadian pattern regardless of the sleep/wake state.

Adult↗

Time of day, repeated testing, and interblock interval effects on P300 amplitude.

Time of day, repeated testing, and interblock interval effects on P300 amplitude were investigated. Subjects (N = 50) were tested using a standard oddball paradigm in either morning or afternoon sessions consisting of six test blocks per session. Amplitude of P300 was significantly higher in the morning than in the afternoon for all test blocks. In addition, amplitude of P300 habituated across test blocks from a mean of 9.59 microV on Block 1 to a mean of 4.98 microV on Block 6. Inserting a one-hour interval between Blocks 2 and 3 attenuated the rate of habituation. The results indicate that time of day, repeated testing, and interblock intervals affect P300 amplitude. Amplitude changes due to time of day may reflect circadian variations in cognitive resources indexed by the P300 component, while decrements due to repeated testing may reflect changes in allocation of resources across test sessions.

Adult↗

Responsiveness to olfactory stimuli presented in sleep.

Whether humans react to olfactory stimuli presented in sleep was assessed. Responses of ten participants (mean age = 22.8 years) were recorded to repeated three-minute periods of either air alone or to a peppermint odor (0.26 mg/liter) during stage 2 sleep. These responses included behavioral (awakening, microswitch closure), autonomic (heart rate, EMG, respiration), and central (EEG) components. An odor delivery system is described comprised of an aquarium pump, Teflon and TYGON tubing, oxygen mask, filtering, and air flow valves. The data indicate that humans react behaviorally, autonomically and centrally to olfactory stimuli presented while sleeping. Although the percentage of overall responsivity to olfactory stimuli was low, significant differences (ANOVA) in responsivity to odor periods vs. nonodor periods were found for microswitch closures, EEG, EMG, and heart rate. For these measures eight or more of the ten participants showed this pattern of differential responsivity during odor and nonodor periods (Sign test = p less than 0.05). A time-of-night effect was also observed in that responsivity tended to be greatest early in the night. The effect on responsivity of other durations, concentrations, and odors requires additional research.

Adult↗

Ultradian rhythms in responsiveness to stimuli presented during sleep.

The present study examined rhythmicity in responding to stimuli presented during sleep. Subjects were trained while awake to respond (by taking a deep breath) to an auditory stimulus that was subsequently presented after every 4 min (8 subjects) or after every 1 min (8 subjects) of continuous sleep. Visual inspection of the response data revealed, for most subjects, a tendency for response latencies to vary rhythmically with 3-5 response cycles per night. Relatively slow, "time-of-night", changes in responsiveness were also seen. Spectral analysis supported the observation of response rhythmicity. Frequency bands with centers corresponding to periods of 133, 100, and 80 min accounted for a significant proportion of the spectral variance for both the 4-min and 1-min group. Sleep was severely disrupted under the 1-min condition, but response rhythmicity was as evident as under the 4-min condition. For subjects having nearly normal sleep structure, the longer latencies in the response cycles tended to occur during nonrapid eye movement periods, while the shorter latencies tended to occur near REM. Response variability during REM often obscured cyclic tendencies. The data suggest that responsiveness during sleep

Acoustic Stimulation↗

Behavioral responsiveness in sleeping older adults.

The control of behavior by stimuli presented during sleep, and related effects on sleep and daytime sleepiness, were investigated in 17 older (age = 60-74 years) adults. Experimental subjects (N = 8) were trained while awake to terminate tone presentations by taking a deep breath. Tones were then presented following sleep onset for four consecutive nights with a mean intertone interval of 4 min. Control subjects (N = 9) slept in the laboratory but did not receive tones. The daytime sleepiness of both groups was assessed by recording latency to sleep onset in a morning and afternoon nap test. It was found that the experimental subjects responded reliably to the tones. Responding, however, was almost invariably accompanied by disruption of sleep and overall sleep structure was markedly altered. Surprisingly, the daytime sleepiness of experimental subjects was not reliably greater than that of control subjects.

Aged↗

Behavioral control of abnormal breathing in sleep.

Behavioral control of abnormal breathing in sleep was studied to determine if an intervention procedure could reduce apnea duration and also SaO2 (blood oxygen) desaturation levels. Sleep apnea patients (n = 11) were instructed while awake that tones would be presented in sleep whenever an apnea event occurred. They were told to breathe deeply to the tones and were given practice in doing so. Intervention and nonintervention hours alternated across 2 nights following 2 baseline nights. As expected, during the intervention hours, the duration but not the frequency of apneic events was reduced. The procedure also resulted in higher SaO2 levels during the intervention hours. Daytime sleepiness was not greater following intervention but sleep staging effects were observed. The results are sufficiently promising to warrant additional research.

Adult↗

Control of masseter muscle tension during sleep.

This study evaluated whether muscle tension could be controlled during sleep. Twelve volunteers were assigned to an experimental condition or to a no treatment control group. Experimental subjects were instructed to reduce the tension in their masseter (jaw) muscle when signalled with an auditory tone. These subjects demonstrated cue-controlled tension reductions during awake training sessions. Although both groups evidenced muscle tension increases in response to the tones presented during sleep, experimental subjects produced significantly smaller increases in response to tone stimuli than did control subjects. More importantly, experimental subjects sustained lower tonic levels of muscle tension throughout the sleep sessions than did control subjects. Sleep was moderately disrupted for subjects in both groups. However, experimental subjects evidenced the greatest tension reductions during those responses in which they shifted to a lighter stage of sleep rather than fully awakening. These data suggest that muscle tension can be moderated during sleep.

Adolescent↗