Functional Connectivity Deficits During Visual Working Memory in First-Episode Psychosis

Scientists specializing in the field of psychosis research have characterized schizophrenia as a syndrome of brain dysconnectivity. Visual working memory, an executive function that relies upon coordinated activity across distributed brain regions to support various cognitive operations, has consistently exhibited impairments in schizophrenia. Indeed, cognitive symptoms account for significant functional and occupational deficits in psychosis, and are present during the early stages of the illness. These cognitive deficits may have subtle manifestations and exhibit greatest sensitivity to increases in cognitive load or task complexity requiring increased executive function.

To improve our understanding of how cognitive load impacts communication across the visual working memory network, a team of researchers including Alfredo Sklar, MD, PhD (Assistant Professor of Psychiatry); Brian Coffman, PhD (Research Instructor in Psychiatry); and Dean Salisbury, PhD (Professor of Psychiatry), from Pitt Psychiatry recently published a study in the Journal of Psychiatric Research examining connectivity within the visual working memory network during first-episode psychosis. 

“The presence of profound working memory deficits in psychosis—and the extensive literature defining the distributed neural systems supporting visual working memory in healthy adults—makes it an excellent model system to examine the consequences of network dysconnectivity in early psychosis,” said Dr. Sklar, the study’s first author. 

The investigators recorded magnetoencephalography (MEG) during a lateralized visual working memory task consisting of low and high memory load conditions to examine load-dependent modulations of alpha-band connectivity in first-episode schizophrenia spectrum individuals. Structural magnetic resonance imaging was obtained separately for each participant to localize MEG activity and identify the synchronized cortical network supporting visual working memory performance. In addition, they explored relationships between the modulation of network connectivity by task load and clinical outcomes. 

Results from the study demonstrated that first-episode schizophrenia spectrum individuals exhibit a load-dependent deficit in visual working memory capacity relative to the unaffected comparison group, and were also unable to enhance connectivity within a portion of the visual working memory network in response to increasing task demands.

Furthermore, first-episode schizophrenia spectrum individuals exhibiting reduced network connectivity experienced greater symptoms of reality distortion.

“The demonstration of impaired brain connectivity with increasing memory and cognitive demands at the first episode of psychosis indicates that distributed brain processing is impaired very early in the disease and manifests in psychotic symptoms and cognitive deficits. However, because structural deficits are minor at this disease stage, the results provide new targets for novel treatment that can improve overall brain function and reduce the ‘circuitopathy’ characteristic of psychosis.” said Dr. Salisbury, the study’s corresponding author. 

Load-dependent functional connectivity deficits during visual working memory in first-episode psychosis
Sklar AL, Coffman BA, Longenecker JM, Curtis M, Salisbury DF.
Journal of Psychiatric Research, Volume 153, 2022, Pages 174-181, ISSN 0022-3956, https://doi.org/10.1016/j.jpsychires.2022.06.042.