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Biomedical subjects

J Allan Hobson

Publications and source records attributed to J Allan Hobson.

At least 19 recordsLinked to original sources

Sleep is of the brain, by the brain and for the brain.

Sleep is a widespread biological phenomenon, and its scientific study is proceeding at multiple levels at the same time. Marked progress is being made in answering three fundamental questions: what is sleep, what are its mechanisms and what are its functions? The most salient answers to these questions have resulted from applying new techniques from basic and applied neuroscience research. The study of sleep is also shedding light on our understanding of consciousness, which undergoes alteration in parallel with sleep-induced changes in the brain.

Animals↗

From synapse to gene product: prolonged expression of c-fos induced by a single microinjection of carbachol in the pontomesencephalic tegmentum.

It is not known how the brain modifies its regulatory systems in response to the application of a drug, especially over the long term of weeks and months. We have developed a model system approach to this question by manipulating cholinergic cell groups of the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei in the pontomesencephalic tegmentum (PMT), which are known to be actively involved in the timing and quantity of rapid eye movement (REM) sleep. In a freely moving feline model, a single microinjection of the cholinergic agonist carbachol conjugated to a latex nanosphere delivery system into the caudolateral PMT elicits a long-term enhancement of one distinguishing phasic event of REM sleep, ponto-geniculo-occipital (PGO) waves, lasting 5 days but without any significant change in REM sleep or other behavioral state. Here, we test the hypothesis that cholinergic activation within the caudolateral PMT alters the postsynaptic excitability of the PGO network, stimulating the prolonged expression of c-fos that underlies this long-term PGO enhancement (LTPE) effect. Using quantitative Fos immunohistochemistry, we found that the number of Fos-immunoreactive (Fos-IR) neurons surrounding the caudolateral PMT injection site decreased sharply by postcarbachol day 03, while the number of Fos-IR neurons in the more rostral LDT/PPT increased >30-fold and remained at a high level following the course of LTPE. These results demonstrate a sustained c-fos expression in response to pharmacological stimulation of the brain and suggest that carbachol's acute effects induce LTPE via cholinergic receptors, with subsequent transsynaptic activation of the LDT/PPT maintaining the LTPE effect.

Animals↗

Sleep quality deteriorates over a binge--abstinence cycle in chronic smoked cocaine users.

RATIONALE: In cocaine dependent individuals, changes in subjective and objective sleep quality accompany their characteristic binge-abstinence cycle. Preliminary studies suggest that sleep quality may decline with prolonged abstinence. Reported here are results of the most extensive study to date on sleep abnormalities during cocaine binge and confirmed abstinence under controlled conditions. OBJECTIVES: The purpose of the current study was to use an experimental, inpatient model of the cocaine binge and abstinence cycle to examine the course and magnitude of sleep disturbances during cocaine use and abstinence. METHODS: Five inpatient non-treatment seeking cocaine users completed 3 baseline days of drug abstinence followed by 3 days of medically monitored "binge" cocaine use, and then 15 days of drug abstinence. Physiological sleep was recorded with polysomnography and the Nightcap ambulatory monitor, while subjective sleep was assessed by questionnaire. RESULTS: Across 3 days of binge cocaine use and 15 subsequent days of confirmed drug abstinence, mean sleep duration, efficiency and latency changed in the direction of poorer sleep quality. In contrast, subjective reports of sleep quality remained unchanged across the same period. CONCLUSIONS: Physiological sleep quality deteriorated from days when cocaine was used across the first 2 weeks of confirmed drug abstinence. In contrast, subjective reports of sleep quality remained unchanged across the same period. We postulate that this dissociation between objective and subjective sleep quality results from a cocaine-use related disruption of the sleep homeostat. Worsening sleep quality during cocaine abstinence may contribute to the risk of relapse and its treatment may offer novel therapeutic strategies for cocaine dependence.

Adult↗

Cognitive performance by humans during a smoked cocaine binge-abstinence cycle.

Five cocaine-dependent individuals completed a 22-day inpatient study of sleep and cognition. Following 3 days of drug-free baseline, participants underwent 3 days of twice-daily smoked cocaine base self-administration (6 50-mg doses, 14 minutes apart), followed by 15 days of abstinence. Each morning and afternoon, the CDR repeatable, multiple-version, computerized cognitive battery (whose stability following practice has been documented) was administered. During abstinence, performance deteriorated on vigilance tasks (especially reaction time) as well as on immediate and delayed verbal recognition tasks but not on working memory tasks. Declines were most evident in the afternoon. Data suggest that abstinence can unmask cognitive deficits induced by chronic cocaine use and circadian factors may mediate their severity.

Adult↗

State-dependent thinking: a comparison of waking and dreaming thought.

Thinking is known to be state dependent but a systematic study of how thinking in dreams differs from thinking while awake has not been done. The study consisted of analyzing the dream reports of 26 subjects who, in addition to providing dream reports also provided answers to questions about their thinking within the dream. Our hypothesis was that thinking in dreams is not monolithic but has two distinct components, one that is similar to wake-state cognition, and another that is fundamentally different. We found that cognition within a dream scenario was similar to that of wake-state cognition, but that thinking about the scenario itself was deficient and very different than wake-state thinking.

Adolescent↗

Eyelid movements measured by Nightcap predict slow eye movements during quiet wakefulness in humans.

A precipitous decline in eyelid movements (ELMs) has been shown to be a highly reliable indicator of sleep onset. While ELMs correlate well with eye movements during waking and rapid eye movement (REM) sleep, the eye sensor remains silent during the period of slow eye movements (SEMs) typical of sleep onset. If the ELM density (e.g. ELMs per minute) dropped simultaneously with the appearance of SEMs prior to sleep onset, it could be a promising tool for identifying decreases in alertness prior to overt sleep onset. The present study was designed to determine whether the presence of SEMs in the transitional period preceding stage 1 sleep is reflected in decreases in ELM density. ELM densities were computed for 2.5-s epochs with and without SEMs, as well as for 15-s epochs. Decreases in ELM density not only were an excellent correlate of the appearance of SEMs during wakefulness with closed eyes, but also a good predictor of their occurrence (c. 82% accuracy) at a time resolution of 2.5 s. Based on these results, we conclude that ELM density reliably predicts moderate changes in the level of alertness during quiet wakefulness.

Adult↗

Thinking and hallucinating: reciprocal changes in sleep.

Internal deliberations (focused thoughts) and endogenous percepts (hallucinations) vary in a reciprocal manner across the states of waking and sleep, paralleling changes in regional brain activation. As subjects go from waking through sleep onset to NREM sleep and then to REM sleep, they report progressively more hallucinoid imagery and progressively less thinking. We have investigated whether this reciprocity in cognition between NREM and REM is maintained throughout the night. To do so, we analyzed 229 REM and 165 NREM reports collected with the Nightcap sleep monitoring system from 16 participants in their homes over 14 nights. The reports were scored for the presence of hallucinations and directed thinking by external judges. As predicted, hallucinations were more frequent in REM than in NREM for each segment of the night, and directed thinking was more frequent in NREM in the first 5 h of the night. Late in the night, directed thinking was equally infrequent in NREM and REM. At the same time, hallucinations increased within both NREM and REM as the night progressed, whereas directed thinking decreased in NREM and remained at a stable, low level in REM. These findings suggest that a reciprocal shift in focused thinking and hallucinating is a general property of cognitive activity across the wake-sleep cycle. Biological evidence supports the hypothesis that these cognitive changes are governed by specific state regulatory and neurocognitive processes at several levels of the brain.

Adult↗

Dissociable stages of human memory consolidation and reconsolidation.

Historically, the term 'memory consolidation' refers to a process whereby a memory becomes increasingly resistant to interference from competing or disrupting factors with the continued passage of time. Recent findings regarding the learning of skilled sensory and motor tasks ('procedural learning') have refined this definition, suggesting that consolidation can be more strictly determined by time spent in specific brain states such as wake, sleep or certain stages of sleep. There is also renewed interest in the possibility that recalling or 'reactivating' a previously consolidated memory renders it once again fragile and susceptible to interference, therefore requiring periods of reconsolidation. Using a motor skill finger-tapping task, here we provide evidence for at least three different stages of human motor memory processing after initial acquisition. We describe the unique contributions of wake and sleep in the development of different forms of consolidation, and show that waking reactivation can turn a previously consolidated memory back into a labile state requiring subsequent reconsolidation.

Fingers↗

Dreaming and episodic memory: a functional dissociation?

The activity that takes place in memory systems during sleep is likely to be related to the role of sleep in memory consolidation and learning, as well as to the generation of dream hallucinations. This study addressed the often-stated hypothesis that replay of whole episodic memories contributes to the multimodal hallucinations of sleep. Over a period of 14 days, 29 subjects kept a log of daytime activities, events, and concerns, wrote down any recalled dreams, and scored the dreams for incorporation of any waking experiences. While 65% of a total of 299 sleep mentation reports were judged to reflect aspects of recent waking life experiences, the episodic replay of waking events was found in no more than 1-2% of the dream reports. This finding has implications for understanding the unique memory processing that takes place during the night and is consistent with evidence that sleep has no role in episodic memory consolidation.

Consciousness↗

The prefrontal cortex in sleep.

Experimental data indicate a role for the prefrontal cortex in mediating normal sleep physiology, dreaming and sleep-deprivation phenomena. During nonrandom-eye-movement (NREM) sleep, frontal cortical activity is characterized by the highest voltage and the slowest brain waves compared to other cortical regions. The differences between the self-awareness experienced in waking and its diminution in dreaming can be explained by deactivation of the dorsolateral prefrontal cortex during REM sleep. Here, we propose that this deactivation results from a direct inhibition of the dorsolateral prefrontal cortical neurons by acetylcholine, the release of which is enhanced during REM sleep. Sleep deprivation influences frontal executive functions in particular, which further emphasizes the sensitivity of the prefrontal cortex to sleep.

Journal Article↗

Emotional experience during rapid-eye-movement sleep in narcolepsy.

STUDY OBJECTIVES: To describe emotional experience during sleep-onset rapid-eye-movement [(REM) SOREM] sleep and nighttime REM in narcoleptic patients and to relate any differences in REM emotion to the more general abnormalities of this disorder. DESIGN: Awakenings were performed from SOREM (REM at the onset of daytime naps and nighttime sleep) and nighttime emergent (ascending) REM in 15 patients with narcolepsy and from nighttime REM in 9 normal healthy participants. Subjects rated the occurrence and intensity of discrete emotion types for each line in their REM-mentation reports. Fragmentation of REM was measured and related to emoton. SETTING: Subjects were studied in their own homes over 2 consecutive days and nights (3 nights for normals) and were monitored by ambulatory polysomnography. PARTICIPANTS: Fifteen patients with narcolepsy, aged 17 to 70 years (mean = 45.3) and 9 normal healthy subjects, aged 31 to 60 years (mean = 43.0). RESULTS: Emotions were found more often and were more intense in narcoleptic SOREM than in nighttime REM of either narcoleptic or normal subjects, with anxiety/fear exhibiting the strongest increase, followed by joy/elation. Comparing nighttime REM in narcoleptic and normal subjects, narcoleptics were found to have more intense feelings of anxiety/fear and of joy/elation but to have a less frequent experience of surprise and anger. Positive and negative emotions occurred in a balanced fashion in SOREM and nighttime REM in narcoleptic subjects. In the SOREM of narcoleptic patients, high levels of positive emotions, in particular of joy/elation, were associated with a less fragmented (more stable) REM sleep. CONCLUSION: The REM sleep of patients with narcolepsy affords a unique opportunity to study emotion and to analyze its psychophysiology. Narcolepsy intensifies REM-dream emotion, especially anxiety/fear and joy/elation, and this is most clearly seen during SOREM sleep. The changes in REM emotion of narcoleptic patients could reflect the effect of the fundamental pathology of this disorder upon neurobiologic systems that support cognitive-emotional functions.

Adolescent↗

Practice with sleep makes perfect: sleep-dependent motor skill learning.

Improvement in motor skill performance is known to continue for at least 24 hr following training, yet the relative contributions of time spent awake and asleep are unknown. Here we provide evidence that a night of sleep results in a 20% increase in motor speed without loss of accuracy, while an equivalent period of time during wake provides no significant benefit. Furthermore, a significant correlation exists between the improved performance overnight and the amount of stage 2 NREM sleep, particularly late in the night. This finding of sleep-dependent motor skill improvement may have important implications for the efficient learning of all skilled actions in humans.

Adolescent↗

Nightcap: a reliable system for determining sleep onset latency.

Previous studies have demonstrated that the Nightcap home-based sleep-monitoring system can differentiate waking, NREM and REM sleep based on eyelid movements (ELMs) and head movement behavior. The present study aims at determining the reliability of the Nightcap in determining the human sleep onset latency (SOL) as revealed by standard polysomnography (PSG). Four naps were recorded in each of ten normal subjects using both PSG and the Nightcap simultaneously. The Nightcap algorithm scored sleep onset as the first of 4 consecutive 30-sec epochs with less than 5 ELMs. The mean percentage of agreement between the Nightcap and PSG was 93% (k = 0.79), and the average absolute difference was 45 sec (13.3% of SOL(PSG)). SOL(NC) differed by less than 1 min in 85% of onsets. Recordings of EEG activity from 90 sec before and after PSG-identified sleep onsets were subjected to spectral analysis. Changes in spectral power in the theta (4-7 Hz) and alpha (8-12 Hz) frequency bands during the transition into light sleep correlated well with eyelid behavior. However, changes in ELM density predicted sleep onset better than did changes in theta and alpha spectral power. These results suggest that the Nightcap may be a potential alternative to the PSG technique in the assessment of SOL in normal subjects.

Adult↗

Emotion and cognition: feeling and character identification in dreaming.

This study investigated the relationship between dream emotion and dream character identification. Thirty-five subjects provided 320 dream reports and answers to questions on characters that appeared in their dreams. We found that emotions are almost always evoked by our dream characters and that they are often used as a basis for identifying them. We found that affection and joy were commonly associated with known characters and were used to identify them even when these emotional attributes were inconsistent with those of the waking state. These findings are consistent with the finding that the dorsolateral prefrontal cortex, associated with short-term memory, is less active in the dreaming compared to the wake brain, while the paleocortical and subcortical limbic areas are more active. The findings are also consistent with the suggestion that these limbic areas have minimal input from the dorsolateral prefrontal cortex in the dreaming brain.

Adolescent↗

Cognitive flexibility across the sleep-wake cycle: REM-sleep enhancement of anagram problem solving.

Flexible or 'fluid' cognitive processes are regarded as fundamental to problem solving and creative ability, requiring a specific neurophysiological milieu. REM-sleep dreaming is associated with creative processes and abstract reasoning with increased strength of weak associations in cognitive networks. REM sleep is also mediated by a distinctive neurophysiological profile, different to that of wake and NREM sleep. This study compared the performance of 16 subjects on a test of cognitive flexibility using anagram word puzzles following REM and NREM awakenings across the night, and waking performances during the day. REM awakenings provided a significant 32% advantage in the number of anagrams solved compared with NREM awakenings and was equal to that of wake time trials. Correlations of individual performance profiles suggest that REM sleep may offer a different mode of problem solving compared with wake and NREM. When early and late REM and NREM awakening data were separated, a dissociation was evident, with NREM task performance becoming more REM-like later in the night, while REM performance remained constant. These data suggest that the neurophysiology of REM sleep represents a brain state more amenable to flexible cognitive processing than NREM and different from that in wake, and may offer insights into the neurocognitive properties of REM-sleep dreaming.

Adolescent↗

Sleep and dream suppression following a lateral medullary infarct: a first-person account.

Consciousness can be studied only if subjective experience is documented and quantified, yet first-person accounts of the effects of brain injury on conscious experience are as rare as they are potentially useful. This report documents the alterations in waking, sleeping, and dreaming caused by a lateral medullary infarct. Total insomnia and the initial suppression of dreaming was followed by the gradual recovery of both functions. A visual hallucinosis during waking that was associated with the initial period of sleep and dream suppression is described in detail. Since the changes in sleep and their recovery are comparable to results of animal experiments, it can be concluded that damage to the medullary brain stem causes extreme but short-lived alterations in conscious state and that substantial recovery occurs even though the damage to the brain stem endures.

Aged↗