Dreams, reality and memory: confabulations in lucid dreamers implicate reality-monitoring dysfunction in dream consciousness.

INTRODUCTION: Dreams might represent a window on altered states of consciousness with relevance to psychotic experiences, where reality monitoring is impaired. We examined reality monitoring in healthy, non-psychotic individuals with varying degrees of dream awareness using a task designed to assess confabulatory memory errors - a confusion regarding reality whereby information from the past feels falsely familiar and does not constrain current perception appropriately. Confabulatory errors are common following damage to the ventromedial prefrontal cortex (vmPFC). Ventromedial function has previously been implicated in dreaming and dream awareness. METHODS: In a hospital research setting, physically and mentally healthy individuals with high (n = 18) and low (n = 13) self-reported dream awareness completed a computerised cognitive task that involved reality monitoring based on familiarity across a series of task runs. RESULTS: Signal detection theory analysis revealed a more liberal acceptance bias in those with high dream awareness, consistent with the notion of overlap in the perception of dreams, imagination and reality. CONCLUSIONS: We discuss the implications of these results for models of reality monitoring and psychosis with a particular focus on the role of vmPFC in default-mode brain function, model-based reinforcement learning and the phenomenology of dreaming and waking consciousness.

Abstinence-related changes in sleep during treatment for cocaine dependence.

BACKGROUND: Former sleep studies among non-treatment seeking chronic cocaine users had captured polysomnographic changes for as long as three weeks of abstinence. METHODS: 20 cocaine dependent participants, randomized to placebo in an ongoing clinical trial, received 12 days of inpatient substance abuse treatment followed by 6 weeks of outpatient cognitive behavioral therapy. Polysomnographic recording was performed on consecutive nights during the 1st and 2nd inpatient and 3rd and 6th outpatient weeks. Number of days abstinent was determined from thrice weekly urine toxicology and self-report. Polysomnographic sleep was compared between study week 1 and 2, using paired t-tests. Trajectory of total sleep time (TST) was modeled both as a linear and a quadratic function of days abstinent. RESULTS: Despite reporting an improvement in overall sleep quality, polysomnographic sleep worsened from week 1 to 2. Among all participants, TST and stage 2 sleep time decreased, while REM sleep latency increased. Among participants who began the study with a positive urine test, there was also a decrease in REM and a trend for decreased slow wave sleep. TST compared to number of days abstinent (up to 54 days) was best fit with a quadratic model (p=0.002), suggesting the possibility of an improvement in total sleep time with extended abstinence. CONCLUSIONS: This is the first polysomnographic characterization of sleep in a large sample of cocaine users in treatment. Present findings confirm earlier results of poor and deteriorating sleep early in abstinence, and raise the possibility of improvement after an extended abstinence.

Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans.

N-methyl-D-aspartate glutamate receptor (NMDA-R) antagonists produce schizophrenia-like positive and negative symptoms in healthy human subjects. Preclinical research suggests that NMDA-R antagonists interfere with the function of gamma-aminobutyric acid (GABA) neurons and alter the brain oscillations. These changes have been hypothesized to contribute to psychosis. In this investigation, we evaluated the hypothesis that the NMDA-R antagonist ketamine produces alterations in cortical functional connectivity during rest that are related to symptoms. We administered ketamine to a primary sample of 22 subjects and to an additional, partially overlapping, sample of 12 subjects. Symptoms before and after the experimental session were rated with the Positive and Negative Syndrome Scale (PANSS). In the primary sample, functional connectivity was measured via functional magnetic resonance imaging almost immediately after infusion began. In the additional sample, this assessment was repeated after 45 min of continuous ketamine infusion. Global, enhanced functional connectivity was observed at both timepoints, and this hyperconnectivity was related to symptoms in a region-specific manner. This study supports the hypothesis that pathological increases in resting brain functional connectivity contribute to the emergence of positive and negative symptoms associated with schizophrenia.

A single-day paradigm of self-regulated human cocaine administration.

UNLABELLED: Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs. METHODS: Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed. RESULTS: Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects ("high") were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses. CONCLUSIONS: These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).

A multistudy analysis of the effects of early cocaine abstinence on sleep.

OBJECTIVE: To describe the sleep patterns of early cocaine abstinence in chronic users by polysomnographic and subjective measures. METHODS: 28 cocaine-dependent participants (ages 24-55) underwent polysomnographic sleep (PSG) recording on the 1st, 2nd and 3rd weeks of abstinence on a research dedicated inpatient facility. Objective measures of total sleep time, total REM time, slow wave sleep, sleep efficiency and a subjective measure (sleep quality) along with demographic data were collected from three different long term research studies over a five year period. Data were reanalysed to allow greater statistical power for comparisons. RESULTS: Progressive weeks of abstinence had main effects on all assessed PSG sleep measures showing decreased total sleep time, REM sleep, stages 1 and 2 sleep, and sleep efficiency; increases in sleep onset and REM latencies and a slight increase in slow-wave sleep time were also present. Total sleep time and slow wave sleep were negatively associated with years of cocaine use. Total sleep time was positively associated with the amount of current ethanol use. Sex differences were found with females having more total REM time and an increase at a near significance level in slow wave sleep. Subjective measures were reported as improving with increasing abstinence over the same time period. CONCLUSIONS: Chronic cocaine users show a general deterioration in objective sleep measures over a three-week period despite an increase in subjective overall sleep quality providing further evidence for "occult insomnia" during early cocaine abstinence.

Intrinsic and extrinsic modulation of a single central pattern generating circuit.

Intrinsic and extrinsic neuromodulation are both thought to be responsible for the flexibility of the neural circuits (central pattern generators) that control rhythmic behaviors. Because the two forms of modulation have been studied in different circuits, it has been difficult to compare them directly. We find that the central pattern generator for biting in Aplysia is modulated both extrinsically and intrinsically. Both forms of modulation increase the frequency of motor programs and shorten the duration of the protraction phase. Extrinsic modulation is mediated by the serotonergic metacerebral cell (MCC) neurons and is mimicked by application of serotonin. Intrinsic modulation is mediated by the cerebral peptide-2 (CP-2) containing CBI-2 interneurons and is mimicked by application of CP-2. Since the effects of CBI-2 and CP-2 occlude each other, the modulatory actions of CBI-2 may be mediated by CP-2 release. Although the effects of intrinsic and extrinsic modulation are similar, the neurons that mediate them are active predominantly at different times, suggesting a specialized role for each system. Metacerebral cell (MCC) activity predominates in the preparatory (appetitive) phase and thus precedes the activation of CBI-2 and biting motor programs. Once the CBI-2s are activated and the biting motor program is initiated, MCC activity declines precipitously. Hence extrinsic modulation prefacilitates biting, whereas intrinsic modulation occurs during biting. Since biting inhibits appetitive behavior, intrinsic modulation cannot be used to prefacilitate biting in the appetitive phase. Thus the sequential use of extrinsic and intrinsic modulation may provide a means for premodulation of biting without the concomitant disruption of appetitive behaviors.

Expression of Kv1.1 delayed rectifier potassium channels in Lec mutant Chinese hamster ovary cell lines reveals a role for sialidation in channel function.

Kv1.1 potassium (K+) channels contain significant amounts of negatively charged sialic acids. To examine the role of sialidation in K+ channel function, Chinese hamster ovary cell lines deficient in glycosylation (Lec mutants) were transfected with rat brain Kv1.1 cDNA. The K+ channel was functionally expressed in all cell lines, but the voltage dependence of activation (V1/2) was shifted to more positive voltages and the activation kinetics were slower in the mutant cell lines compared with control. A similar positive shift in V1/2 was recorded in control cells expressing Kv1.1 following treatment with sialidase or by raising extracellular Ca2+. In contrast, these treatments had little or no effect on the Lec mutants, which indicates that channel sialic acids appear to be the negative surface charges sensitive to Ca2+. The data suggest that sialic acid addition modifies Kv1.1 channel function, possibly by influencing the local electric field detected by its voltage sensor, but that these carbohydrates are not required for cell surface expression.