Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG

Author:

Rubinstein Daniel Y12,Eisenberg Daniel P12,Carver Frederick W3,Holroyd Tom3,Apud Jose A2,Coppola Richard23,Berman Karen F12

Affiliation:

1. Section on Integrative Neuroimaging, National Institute of Mental Health, Intramural Research Program, NIH, DHHS , Bethesda, MD , USA

2. Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS , Bethesda, MD , USA

3. MEG Core Facility, NIH, DHHS , Bethesda, MD , USA

Abstract

Abstract Background and Hypothesis We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients. Study Design Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14–30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients. Study Results Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses–the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients’ neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls. Conclusions These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis.

Funder

Intramural Research Program of the National Institute of Mental Health

Publisher

Oxford University Press (OUP)

Subject

Psychiatry and Mental health

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