Abstract
Working memory (WM) deficits have been repeatedly observed in people with schizophrenia (PSZ) and their unaffected biological relatives (REL). Given the apparent association with genetic liability for schizophrenia, WM deficits have been proposed as a potential endophenotype for the disorder. Abnormal neural responses during WM performance have likewise been observed in PSZ and REL and may reflect the expression of genetic liability for schizophrenia in brain function. Relatively recent investigations have examined the role of neural oscillatory activity during visuospatial WM function in healthy people, as well as dysfunction in psychopathology. This research was in part motivated by a neural model of WM proposed by Lisman and Idiart (Science 267:1512–1515, 1995) that delineated a mechanism for representing multiple stimuli within WM through systematic interactions between neural oscillations in the theta- and gamma- frequency ranges. Aberrant oscillatory activity in theta and gamma frequency ranges has since been proposed as a potential underlying factor in WM dysfunction in PSZ and REL. The experimental evidence derived from studies of healthy people that pertains to the theta-gamma model of WM is reviewed herein. Although scarce, direct examinations of theta-gamma interactions in PSZ and REL are likewise reviewed in addition to reports of separate deficits in theta and gamma frequencies observed in PSZ during WM. The implications of theta and gamma oscillatory deficits reported in PSZ are discussed in the context of the Lisman and Idiart (Science 267:1512–1515, 1995) model, as well as how these deficits may result in aberrant theta-gamma interactions that give rise to visuospatial WM dysfunction. Given evidence supporting the Lisman and Idiart (Science 267:1512–1515, 1995) model of theta-gamma interactions in WM and the lack of direct exploration of the model in schizophrenia, there is an imperative to carry out formal testing of theta-gamma interactions in PSZ and REL during WM.
Highlights
Visuospatial working memory (WM), comprised by the coordination of processing, maintaining, manipulating, and retrieving spatial and visual information within the brain [1], has been implicated in a variety of tasks necessary for the navigation of dayto-day life, including wayfinding [2] and visuomotor learning [3, 4]
people with schizophrenia (PSZ) have been found to demonstrate deficits in event-related potential (ERP) elicited from Working memory (WM) tasks [17,18,19] and tasks probing sustained attention [20,21,22,23,24], among others; similar deficits have been observed in first-degree relatives of people with the disorder [22, 25, 26]
This study provides evidence for preserved theta-gamma phase-amplitude coupling in PSZ; given the minimal role WM plays in the oddball paradigm, the theta-gamma interactions examined in this study may be distinct from those related to WM
Summary
Visuospatial working memory (WM), comprised by the coordination of processing, maintaining, manipulating, and retrieving spatial and visual information within the brain [1], has been implicated in a variety of tasks necessary for the navigation of dayto-day life, including wayfinding [2] and visuomotor learning [3, 4]. WM working memory, TGC theta-gamma coupling, iEEG intracranial EEG, LFP local field potential, CSD current source density, EC entorhinal cortex, HFO high-frequency oscillation, ACC anterior cingulate cortex, PFC prefrontal cortex
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