Functional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis

Abstract

Introduction: Semantic verbal fluency (SVF) impairments are debilitating and present early in the course of psychotic illness. Deficits within frontal, parietal, and temporal brain regions contribute to this deficit, as long-range communication across this functionally integrated network is critical to SVF. This study sought to isolate disruptions in functional and structural connectivity contributing to SVF deficits during first-episode psychosis in the schizophrenia spectrum (FESz).

Methods: Thirty-three FESz and 34 matched healthy controls (HC) completed the Animal Naming Task to assess SVF. Magnetoencephalography was recorded during an analogous covert SVF task, and phase-locking value (PLV) used to measure functional connectivity between inferior frontal and temporoparietal structures bilaterally. Diffusion imaging was collected to measure fractional anisotropy (FA) of the arcuate fasciculus, the major tract connecting frontal and temporoparietal language areas.

Results: SVF scores were lower among FESz compared to HC. While PLV and FA did not differ between groups overall, FESz exhibited an absence of the left-lateralized nature of both measures observed in HC. Among FESz, larger right-hemisphere PLV was associated with worse SVF performance (ρ = -0.51) and longer DUP (ρ = -0.50).

Discussion: In addition to worse SVF, FESz exhibited diminished leftward asymmetry of structural and functional connectivity in fronto-temporoparietal SVF network. The relationship between theta-band hyperconnectivity and poorer performance suggests a disorganized executive network and may reflect dysfunction of frontal cognitive control centers. These findings illustrate an aberrant pattern across the distributed SVF network at disease onset and merit further investigation into development of asymmetrical hemispheric connectivity and its failure among high-risk populations.

Keywords: Connectivity; Duration of untreated psychosis; First-episode psychosis; Magnetoencephalography; Semantic fluency; diffusion spectral imaging.