Biology subjects

Law, R. G.

Publications and source records attributed to Law, R. G..

3 recordsLinked to original sources

bioRxiv2021

Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key NREM sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 130 schizophrenia (SCZ) patients and controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that only slow spindles predicted symptom severity, and that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.

neuroscience↗

bioRxiv2020

A group refactorization procedure for sleep electroencephalography

[WORKING DRAFT] In order to relate health and disease to brain state, patterns of activity in the brain must be phenotyped. In this regard, polysomnography datasets present both an opportunity and a challenge, as although sleep data are extensive and multidimensional, features of the sleep EEG are known to correlate with clinical outcomes. Machine learning methods for rank reduction are attractive means for bringing the phenotyping problem to a manageable size. The whole-night power spectrogram is nonnegative, and so applying nonnegative matrix factorization (NMF) to separate spectrograms into time and frequency factors is a natural choice for dimension reduction. However, NMF converges differently depending on initial conditions, and there is no guarantee that factors obtained from one individual will be comparable with those from another, hampering inter-individual analysis. We therefore reseed time-frequency NMF with group frequency factors obtained from the entire sample. This "refactorization" extends classical frequency bands to frequency factors. The group reseeding procedure coerces factors into equivalence classes, making them comparable across individuals. By comparing frequency factor properties, we illustrate age-related effects on the sleep EEG. The procedure can presumably be adapted to higher resolutions, e.g. to local field potential datasets, for characterizing individual time-frequency events.

bioinformatics↗

bioRxiv2019

A supragranular nexus for the effects of neocortical beta events on human tactile perception

Transient neocortical events with high spectral power in the 15-29Hz beta band are among the most reliable predictors of sensory perception: High prestimulus beta event rates in primary somatosensory lead to sensory suppression, most effective at 100-300ms prestimulus latency. However, the synaptic and neuronal mechanisms inducing betas perceptual effects have not been completely localized. We combined human MEG with neural modeling designed to account for these macroscale signals to interpret the cellular and circuit mechanisms that underlie the influence of beta on tactile detection. Extending prior studies, we modeled the hypothesis that higher-order thalamic bursts, sufficient for beta event generation in cortex, recruit supragranular GABAB inhibition acting on a 300ms time scale to suppress sensory information. Consistency between model and MEG data supported this hypothesis and led to a further prediction, validated in our data, that stimuli are perceived when beta events occur simultaneously with tactile stimulation. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.\n\nSignificance statementSomatosensory beta events - transient 15-29Hz oscillations in electromagnetic recordings - are thought to be generated when \"top-down\" bursts of spikes presumably originating in higher-order thalamus arrive in upper layers of somatosensory cortex. Physiological evidence had shown that the immediate action of these top-down projections should be excitatory; however, after a beta event, sensory perception is noticeably inhibited for approximately 300ms. The source of this post-event sensory suppression, in particular, had been unresolved. Using a detailed computational model of somatosensory cortex, we find evidence for the hypothesis that these bursts couple indirectly to GABAB inhibition in upper layers of cortex, and that beta events first briefly disinhibit sensory relay before a longer period of inhibition.

neuroscience↗