Mohammad Zia Ul Haq Katshu

Slow wave sleep deficits as a trait marker in patients with schizophrenia

BACKGROUND Among the sleep abnormalities found in schizophrenia, slow wave sleep deficits have been found to persist even after the resolution of active psychotic symptoms. Further, such abnormalities are observed in young healthy individuals at high risk of schizophrenia, which suggest that slow wave sleep deficits might be trait marker in schizophrenia. METHODS Sleep EEG was recorded in 20 right handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14 first degree relatives and 20 age and sex matched controls. Patients were rated on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) for assessment of psychopathology. RESULTS There was significant difference between the three groups in total sleep period (p<.01), total sleep time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant positive correlation of REM percentage of total sleep time with BPRS total score (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas significant negative correlation of REM latency was found with BPRS total score (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the patients. CONCLUSIONS Slow wave sleep deficits are a possible trait marker in patients with schizophrenia, which needs replication in further studies.

Comparison of Anticraving Efficacy of Right and Left Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized Double-Blind Study

The objective of this study was to compare the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right versus left dorsolateral prefrontal cortex (DLPFC) in patients with alcohol dependence. Twenty patients with alcohol dependence syndrome were randomly allocated to receive either right or left rTMS over the right DLPFC (10 sessions at 10 Hz frequency; 20 trains per session; 4.9 seconds per train and intertrain interval 30 seconds) and were assessed on the Alcohol Craving Questionnaire (ACQ-NOW) to measure craving. Two-way repeated-measures analysis of variance for ACQ-NOW total score showed no main effect of group (F[1,18] = 0.0001 but significant main effect of time (F[1,18] = 185.91, p<0.0001, η(2) = 0.912). The interaction effect between group and time was not significant. There was significant reduction in craving scores in patients receiving either right or left rTMS with large effect size. However, there was no difference in anticraving efficacy between the two groups.

Increased spontaneous gamma power and synchrony in schizophrenia patients having higher minor physical anomalies.

The higher frequency of minor physical anomalies (MPAs) in schizophrenia provides morphological evidence for the neurodevelopmental theory. Abnormal gamma oscillations (>30 Hz) seen in the electroencephalogram (EEG) in schizophrenia have been hypothesized to result from developmental insults. This study investigated spontaneous gamma oscillations in schizophrenia patients having higher and lower number of MPAs. Forty drug naïve/free schizophrenia patients and 20 matched healthy controls were assessed for MPAs on the Extended Waldrop Scale (EWS). All participants underwent an awake, resting 192-channel EEG recording. Spontaneous gamma spectral power and coherence were estimated in the low- (30-50 Hz) and high-gamma (51-70 and 71-100 Hz) bands. Significantly higher power was observed in high-MPA than healthy control group in low-gamma band over right frontal, parietal and temporal regions. Spectral power in the high-gamma band (71-100 Hz) was also significantly higher in the high-MPA schizophrenia subgroup than in the healthy control group over left frontal, parietal and temporal regions. Additionally, regional intra-hemispheric and inter-hemispheric coherence in the low-gamma band was significantly higher in the high-MPA schizophrenia subgroup than on the healthy control group. This study is the first to provide evidence of increased spontaneous gamma power and synchrony in schizophrenia patients having higher MPAs, supporting the idea that it may represent a distinct subgroup of schizophrenia with a neurodevelopmental basis.

Abnormal visuomotor processing in schizophrenia

Subtle disturbances of visual and motor function are known features of schizophrenia and can greatly impact quality of life; however, few studies investigate these abnormalities using simple visuomotor stimuli. In healthy people, electrophysiological data show that beta band oscillations in sensorimotor cortex decrease during movement execution (event-related beta desynchronisation (ERBD)), then increase above baseline for a short time after the movement (post-movement beta rebound (PMBR)); whilst in visual cortex, gamma oscillations are increased throughout stimulus presentation. In this study, we used a self-paced visuomotor paradigm and magnetoencephalography (MEG) to contrast these responses in patients with schizophrenia and control volunteers. We found significant reductions in the peak-to-peak change in amplitude from ERBD to PMBR in schizophrenia compared with controls. This effect was strongest in patients who made fewer movements, whereas beta was not modulated by movement in controls. There was no significant difference in the amplitude of visual gamma between patients and controls. These data demonstrate that clear abnormalities in basic sensorimotor processing in schizophrenia can be observed using a very simple MEG paradigm.

Human Parahippocampal Cortex Supports Spatial Binding in Visual Working Memory.

Abstract Studies investigating the functional organization of the medial temporal lobe (MTL) suggest that parahippocampal cortex (PHC) generates representations of spatial and contextual information used by the hippocampus in the formation of episodic memories. However, evidence from animal studies also implicates PHC in spatial binding of visual information held in short term, working memory. Here we examined a 46‐year‐old man (P.J.), after he had recovered from bilateral medial occipitotemporal cortex strokes resulting in ischemic lesions of PHC and hippocampal atrophy, and a group of age‐matched healthy controls. When recalling the color of 1 of 2 objects, P.J. misidentified the target when cued by its location, but not shape. When recalling the position of 1 of 3 objects, he frequently misidentified the target, which was cued by its color. Increasing the duration of the memory delay had no impact on the proportion of binding errors, but did significantly worsen recall precision in both P.J. and controls. We conclude that PHC may play a crucial role in spatial binding during encoding of visual information in working memory.

Evaluation of spontaneous dense array gamma oscillatory activity and minor physical anomalies as a composite neurodevelopmental endophenotype in schizophrenia.

Minor physical anomalies (MPAs) and gamma oscillatory activity have been proposed as associated endophenotypes in schizophrenia. Combining these endophenotypes to create a composite endophenotype may help identify those at risk for schizophrenia better. The present study aims to investigate MPAs and gamma oscillatory activity in schizophrenia patients, their unaffected first degree relatives and healthy controls and appreciate whether they can be used together as a composite endophenotype.

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with “residual schizophrenia”, in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione–glutamate component; an insula-visual glutathione–glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione–glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response.

T144. THE ROLE OF TRANSIENT BETA OSCILLATIONS IN ABERRANT SELECTIVE ATTENTION TO SALIENT EVENTS IN SCHIZOPHRENIA

Abstract Background Selective attention to situationally salient information is aberrant in schizophrenia. Following the presentation of behaviourally relevant stimuli, oscillatory power in the beta-band (13-30Hz) typically decreases (Event-Related Desynchronisation – ERD) then increases (Event-Related Synchronisation – ERS). The ERD-ERS pattern is a potential marker for the processing of behaviourally salient events. In a previous magnetoencephalography (MEG) study (Liddle et al Hum. Brain Mapp. 2016; 37:1361–74) we found that in people with schizophrenia, ERS was reduced. Recently, Jones (Curr. Opin. Neurobiol, 2016; 40: 72–80) proposed that the relatively continuous beta-synchronisation observed in trial-averaged data may reflect the probability distribution of transient beta events discernible in single trial data. She cited both animal and human data consistent with a neural model in which these beta bursts are generated by transient input to pyramidal neurons via distal dendrites concurrent with input to deeper layers presumed to be from thalamus. External stimuli are less likely to be perceived during the time period immediately following a transient beta event. The model is consistent with the hypothesis that transient beta bursts are an index of top-down modulation of the processing of perceptual information, and raises the possibility that aberrant control over this modulation might contribute to aberrant selective attention in schizophrenia. We hypothesized that in relevant trials, the beta-burst probability distribution would be skewed towards the latter part of the trial, reflecting a period of suppressed beta-burst probability, and thus of enhanced stimulus perception, followed by a period of increased burst probability, possibly reflecting sensory suppression following stimulus processing. Methods We recorded MEG data in 23 patients with schizophrenia and 37 healthy controls during the performance of a relevance modulation task designed to assess neural effects of situational salience. Data were recorded using a 275-channel CTF system (Coquitlam, Canada). Visual stimuli that were either task-relevant or task-irrelevant were presented in alternating, predictable, order. Beamformed data time courses were computed for 8 previously defined brain networks. Time-frequency spectrograms were computed for each trial, from 0 to 1500 ms following stimulus presentation. A 2-D peak-detection algorithm was used to identify transient increases in oscillatory power. The time point of any peak occurring within the beta band (~15–25 Hz) was recorded, and the median of these time-points computed for each trial. These medians were averaged within each participant for each trial type (relevant; irrelevant) as a measure of central tendency of the probability distribution of the beta-bursts. Results On average, between one or two beta-bursts were recorded per trial. As predicted, these occurred significantly later during behaviorally relevant trials than during irrelevant trials, in all networks, F(1,58)= 93.5, p<0.001), consistent with normal post-event beta enhancement. This effect was significantly attenuated in schizophrenia, F(1,58)=6.01, p=.017. Discussion These findings add to the evidence that patients with schizophrenia have reduced ability to allocate attention to behaviorally relevant information. Furthermore, the demonstration of an abnormality potentially accounted for by neural modelling of top-down influence on perceptual processing opens the way to understanding the relevant neural mechanism and to developing neuromodulatory treatments that might alleviate aberrant selective attention in schizophrenia.

36 Human parahippocampal cortex supports spatial binding in visual working memory

Objective Studies investigating the functional organisation of the medial temporal lobe (MTL) suggest that parahippocampal cortex (PHC) generates representations of spatial and contextual information used by the hippocampus in the formation of episodic memories. However, evidence from animal studies also implicates PHC in spatial binding of visual information held in working memory. This study focussed on elucidating the role of PHC in spatial binding in working memory in humans. Method We assessed a 46-year-old man (PJ), after he had recovered from bilateral medial occipitotemporal cortical mOTC strokes resulting in lesions in PHC but sparing the hippocampus, and a group of age-matched healthy controls on a series of visual working memory tasks. Results When recalling the colour of one of two objects, PJ misidentified the target when cued by its location, but not shape. When recalling the position of one of three objects, he frequently misidentified the target, which was cued by its colour. Increasing the duration of the memory delay had no impact on the proportion of binding errors, but did significantly worsen recall precision in both PJ and controls. Conclusion We conclude that PHC plays a crucial role in spatial binding during encoding of visual information in working.