Peter Fenwick

Alcohol and Sleep I: Effects on Normal Sleep

This review provides a qualitative assessment of all known scientific studies on the impact of alcohol ingestion on nocturnal sleep in healthy volunteers. At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep and an increase in sleep disruption in the second half of sleep. The effects on rapid eye movement (REM) sleep in the first half of sleep appear to be dose related with low and moderate doses showing no clear trend on REM sleep in the first half of the night whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percentage is decreased in the majority of studies at moderate and high doses with no clear trend apparent at low doses. The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep followed by the reduction in total night REM sleep. The majority of studies, across dose, age and gender, confirm an increase in slow wave sleep (SWS) in the first half of the night relative to baseline values. The impact of alcohol on SWS in the first half of night appears to be more robust than the effect on REM sleep and does not appear to be an epiphenomenon REM sleep reduction. Total night SWS is increased at high alcohol doses across gender and age groups.

Widely Distributed Magnetoencephalography Spikes Related to the Planning and Execution of Human Saccades

With sufficiently fast data sampling, ubiquitous sharp transients appear in magnetoencephalography (MEG) data. Initially, no known collective neuronal activity could explain MEG signal generation well above 100 Hz, so it was assumed that these transients were entirely composed of background electronic noise that could be eliminated by filtering and averaging. Recent studies at the cellular level provided evidence for synchronous synaptic input to dendrites and volleys of near-simultaneous action potentials. MEG studies have also identified high-frequency oscillations well above 200 Hz after averaging large number of somatosensory evoked responses. In this study, we searched for evidence of high-frequency neuronal activity in the raw MEG signal using the highest sampling rate available with our hardware. Two human subjects participated in three experiments using visual cues to define planning, preparation, and execution or inhibition of saccades. Tomographic analysis identified “MEG spikes” that were widely distributed across the cortex, cerebellum, and brainstem during cue presentations and saccades. Here we demonstrate how these MEG spikes can be recorded and localized in real time and show that task demands influence their properties. The MEG spikes were organized into feedforward and corollary discharge sequences that could, when combined with the slower activity-linked processing in discrete brain areas over long periods, lasting hundreds of milliseconds. Preparation for impending saccade began as soon as relevant information became available. Cues providing partial information initiated competing motor programs for as yet undecided future actions that were maintained until cues with new information resolved the uncertainty.

Repetitive and non-repetitive violent offending behaviour in male patients in a maximum security mental hospital--clinical and neuroimaging findings.

Objective: To examine if different violent offending behaviours are associated with different clinical and neuroimaging profiles. Method: Thirty-nine schizophrenic and schizoaffective offenders from a maximum security mental hospital – 20 repetitive violent offenders (RVOs) and 19 non-repetitive violent offenders (NRVOs) – were selected for clinical and neuroimaging assessments. Results: Both groups had positive family history of mental illness and violence. Age, diagnosis, duration of illness, victim profiles and use of weapons at the time of the index offence were similar. RVOs had a higher prevalence of early parental separation, juvenile conduct problem, previous convictions of crimes not involving violence, impulsive suicide attempts, delusion of their lives being threatened at the time of the index offence and electroencephalographic (EEG) abnormalities localized to temporal lobes. NRVOs had a higher prevalence of sexual inexperience and command hallucinations to kill at the time of the index offence. Asymmetric gyral patterns at the temporo-parietal region were particularly common in RVOs and absent in NRVOs. Non-specific white matter changes in magnetic resonance imaging (MRI) and generalized cortical hypometabolism in positron emission tomography (PET) were present in both groups. Conclusions: Different structural and metabolic changes in the brain were associated with different violent offending behaviours. The complex interaction between violent behaviour, clinical features and neuroimaging findings in schizophrenia requires further studies.

Averaged and single‐trial analysis of cortical activation sequences in movement preparation, initiation, and inhibition

We compare estimates of three‐dimensional brain activity extracted from averaged and from selected single‐trial magnetoencephalographic signals, in order to study activation sequences related to motor preparation, inhibition, and movement, cued on two tones (S1 and S2). We studied all possible hand‐ear combinations in a right‐handed subject in both initiation and inhibition, and found some marked differences between combinations. Averaging revealed activity in the right motor cortex in all combinations requiring movement inhibition, irrespective of laterality of finger and ear, and in the contralateral motor cortex during movement (but considerably reduced for the task with the practiced ear and finger). These activation patterns are seen in single trials with variability of latency but not position. In the average signal, a long silent period between the warning and imperative stimuli is seen; in single trials, however, recurring sequences of activation linking frontal and posterior areas are seen throughout the analysis period in all combinations. These results show that single‐trial analysis is needed to understand all the significant neural correlates of this task.

EEG responses to visual erotic stimuli in men with normal and paraphilic interests

Contingent negative variation and evoked potentials to visual erotic stimuli were recorded from 8 brain sites in a sample of 62 right-handed men aged 20–50, half of whom declared paraphilic interests and half claimed “normal” heterosexual interests. To quantify erotic preferences, a “variance quotient” (VQ) was calculated from scores on the Wilson Sex Fantasy Questionnaire using the formula VQ = Impersonal + Sadomasochistic fantasies/Intimate + Exploratory fantasies. Stimuli consisted of 57 paraphilic slides (depicting fetishistic and sadomasochistic themes), 57 heterosexual erotic slides (explicit pictures of nude women, coitus, and oral sex), and 57 neutral slides (landscapes and street scenes). The P600 response appeared to be the best indicator of erotic preferences, but the locus of maximum arousal was different for paraphilic and heterosexual stimuli. The primary brain site for heterosexual arousal was P4 (right parietal), where there was a −.34 (p < .01) correlation between VQ and P600 (i.e., nonvariant males showed greater responses to normal erotic stimuli at this location). For paraphilic stimuli, there was a correlation of .26 (p < .05) between the VQ and P600 response at the F3 (left frontal) site (i.e., paraphilic men showed greater responses to paraphilic stimuli than normal men at this brain location). Dividing the sample into groups of 23 paraphilics and 23 heterosexual controls on the basis of their VQs showed that “normals” differentiated between stimulus types more at the P4 than paraphilics. Theoretical and clinical implications of these findings are discussed.

Imaging cerebellum activity in real time with magnetoencephalographic data

The cerebellum has traditionally been associated with motor movements but recent studies suggest its involvement with fine timing, sensory analysis and cognition. Much of the new data comes from neuroimaging techniques such as fMRI and PET, which have high spatial resolution and show that for even simple stimuli many cerebellar and cortical areas are involved. We use examples from recent studies to demonstrate that magnetic field tomography (MFT) offers a new and powerful tool for studying cerebellar function through real time localization of cortical, brainstem and cerebellar activations over timescales ranging from a fraction of a millisecond to seconds, minutes and hours. The examples include demonstration of cerebellar activations along well-established anatomical pathways during saccades and the visualization of the ascending medullar volley after median nerve stimulation. MFT analysis of single trial MEG signals elicited by the presentation of faces in emotion and object recognition tasks, show changes in cerebellar activation between schizophrenics and normal subjects in agreement with proposals for disturbed cerebellar function in schizophrenia. The ability of MFT to identify cerebellar, brainstem and cortical activations in real time can add new insights about dynamics of brain activity to the recent findings about cerebellar function from PET and fMRI.

Sleep-related automatism and the law

Crimes carried out during or arising from sleep highlight many difficulties with our current law and forensic sleep medicine clinical practice. There is a need for clarity in the law and agreement between experts on a standardised form of assessment and diagnosis in these challenging cases. We suggest that the time has come for a standardised, internationally recognised diagnostic protocol to be set as a minimum standard in all cases of suspected sleep-related forensic cases. The protocol of a full medical history, sleep history, psychiatric history, neuropsychiatric and psychometric examination and electroencephalography (EEG), should be routine. It should now be mandatory to carry out routine polysomnography (PSG) to establish the presence of precipitating and modulating factors. Sleepwalking is classified as insane automatism in England and Wales and sudden arousal from sleep in a non-sleepwalker as sane automatism. The recent case in England of R v. Lowe (2005) highlights these anomalies. Moreover, the word insanity stigmatises sleepwalkers and should be dropped. The simplest solution to these problems would be for the law to be changed so that there is only one category of defence for all sleep-related offences – not guilty by reason of sleep disorder. This was rejected by the House of Lords for cases of automatism due to epilepsy, and is likely to be rejected for sleepwalkers. Removing the categories of automatism (sane or insane) would be the best solution. Risk assessment is already standard practice in the UK and follow up, subsequent to disposal, by approved specialists should become part of the sentencing process. This will provide support for the defendant and protection of the public.

Sleep related violence, alcohol and sleepwalking

Sir, We read with interest the review article in Brain by Siclari et al . (2010). Although the authors cite some relevant studies, in our opinion, they do not adequately discuss the possible causal link between alcohol ingestion and disorders of arousal. Siclari and colleagues state ‘criteria for establishing the putative role of an underlying sleep disorder in a specific violent act have been proposed by Mahowald and coworkers (1990)’; and the authors partially reproduce, as Table 4 at page 3505, material from that earlier publication including the statement: ‘Alcohol or drug intoxication precludes the use of disorder of arousal in forensic cases’. Our reading of the cited paper from 1990, involving several of the same authors, is subtly different: ‘To assist in the determination of the putative role of an underlying sleep disorder in a specific …

Interocular yoking in human saccades examined by mutual information analysis

Background Saccadic eye movements align the two eyes precisely to foveate a target. Trial-by-trial variance of eye movement is always observed within an identical experimental condition. This has often been treated as experimental error without addressing its significance. The present study examined statistical linkages between the two eyes’ movements, namely interocular yoking, for the variance of eye position and velocity. Methods Horizontal saccadic movements were recorded from twelve right-eye-dominant subjects while they decided on saccade direction in Go-Only sessions and on both saccade execution and direction in Go/NoGo sessions. We used infrared corneal reflection to record simultaneously and independently the movement of each eye. Quantitative measures of yoking were provided by mutual information analysis of eye position or velocity, which is sensitive to both linear and non-linear relationships between the eyes’ movements. Our mutual information analysis relied on the variance of the eyes movements in each experimental condition. The range of movements for each eye varies for different conditions so yoking was further studied by comparing GO-Only vs. Go/NoGo sessions, leftward vs. rightward saccades. Results Mutual information analysis showed that velocity yoking preceded positional yoking. Cognitive load increased trial variances of velocity with no increase in velocity yoking, suggesting that cognitive load may alter neural processes in areas to which oculomotor control is not tightly linked. The comparison between experimental conditions showed that interocular linkage in velocity variance of the right eye lagged that of the left eye during saccades. Conclusions We conclude quantitative measure of interocular yoking based on trial-to-trial variance within a condition, as well as variance between conditions, provides a powerful tool for studying the binocular movement mechanism.

Alcohol and sleep review: sound statistics and valid conclusions.

HANK YOU FOR forwarding to us the letter fromPressman and colleagues (2015) and for inviting ourresponse.The role of alcohol and its impact on sleep has been stud-ied for more than a century, and a substantial knowledgebase has been created. The studies, like most scientific stud-ies, are dependent on the technology available at the timeandtheavailabilityofdata.Thisissomethingwetookintoconsiderationwhenprepar-ing our qualitative review on the impact of alcohol on nor-malsleep.Theissuesraisedcanbesummarizedasfollows:1. The use of percentages to represent the difference inthe mean values of sleep architecture variables in ourtables,2. Our results and conclusions as they pertain to the impactofalcohol onslowwavesleep(SWS),3. Ourinclusion–exclusioncriteriaforstudies,and4. Alcohol, N3, sleepwalking, and medico-legal conse-quences.1. The use of the mean value as a percentage to representsleeparchitecturevariables:1.1. In our article, we made clear how we have presentedthedata:Valuesforsleep architecturevariablesareprovidedinper-centage terms only. Where the researchers have reportedsleep stage data in minutes we have converted these intopercentages. Some variables, such as sleep onset latencyand rapid eye movement onset latency are reported inminutes only. Only the mean value is displayed for allvariables in the tables to enable a uniform approachthroughout(Ebrahimet al.,2013).1.2. This was accepted by the Journal and the peerreviewers as this review was based on highlighting 2specificareas:1.2.1. The impact of various alcohol doses and their tim-ing on nocturnal sleep in healthy controls and nor-mal populations.1.2.2. The impact of these alcohol doses on various sleepstages.1.3. Asthis was a qualitative reviewand not a quantitativemeta-analysis, it was our aim to provide a broadunderstanding to the “nonsleep specialist”readershipoftheimpactofalcoholonsleep.1.4. Furthermore, in routine clinical practice, sleepstages are reported both in actual time and as apercentage of total sleep, a simple difference in themeans between alcohol and placebo nights wasthought to be the best way to demonstrate theeffect.2. Alcohol andSWS:2.1. Alcohol andfirsthalfofnightSWS(N3):2.1.1. Low dose alcohol studies—Of the 4 studiesreported, 2 showed a significant increase in SWS(MacLean and Cairns, 1982; Van Reen et al., 2011)and the other 2 studies failed to find a significantdifference;2.1.2. Moderatedose studies—Ofthe 5 studies reported,2studies demonstrated a significant increase in SWS(Roehrs et al., 1999; Williams et al., 1983). Theother3 studiesfailedtodemonstrateany significantfindings;2.1.3. High dose studies—Five of the 9 studies reported astatistically significant increase in SWS with alco-hol (Arnedt et al., 2011; Feige et al., 2006;MacLean and Cairns, 1982; Prinz et al., 1980; Wil-liams et al., 1983) and 4 studies did not show anysignificantdifferences.The direction of evidence confirms that at low and moder-ate doses alcohol is not clearly associated with increased