Altered prefrontal activity and connectivity predict different cognitive deficits in schizophrenia

Authors:

Ferrarelli F; Riedner BA; Peterson MJ; Tononi G. Institution Ferrarelli,Fabio. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin. Ferrarelli,Fabio. Department of Psychiatry, University of Pittsb urgh, Pittsburgh, Pennsylvania. Riedner,Brady A. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin. Peterson,Michael J. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin. Tononi,Giulio. Department of Psychiatry, University of Wis consin-Madison, Madison, Wisconsin.

Title:

Altered prefrontal activity and connectivity predict different cognitive deficits in schizophrenia.

Source:

Human Brain Mapping. 36(11):4539-52, 2015 Nov.

Abstract

BACKGROUND: Cognitive dysfunction is considered a core featur e of schizophrenia, and impaired performances in episodic memory (E M) and executive function (EF) tasks are consistently reported in schi zophrenia patients. Traditional fMRI and EEG studies have helped identif ying brain areas, including the prefrontal cortex (PFC), involved in these tasks. However, it is unclear whether intrinsic defects in prefront al function per se contribute to poor performance in schizophrenia, gi ven the presence of confounds like reduced motivation and psychotic sympto ms. TMS/hd- EEG measurements are obtained without cognitive effort, and can be calculated in any cortical area.

METHODS: We performed TMS/hd-EEG recordings in parietal, motor, premotor, and PFC in healthy individuals (N=20) and schizophrenia p atients (N=20). Source modeling of TMS-evoked responses was performed, and measures of cortical activity (significant current density, SCD) and c onnectivity (significant current scattering, SCS) were computed. Patients w ith schizophrenia also performed Penn Word memory delayed (CPWd) and Penn Conditional Exclusion Test (PCET). CPWd evaluates EM and in volves primarily PFC, whereas PCET reflects EF and implicates PFC with o ther brain regions. FINDINGS: We found no difference in SCD and SCS after TMS of parietal/motor cortices, whereas those parameters were reduced in premotor/prefrontal areas in schizophrenia patients. In PFC, where these measures were most defective, SCD was negatively correlated with performance in CPWd whereas higher SCS values were associated with more errors in PCET.

CONCLUSION: These findings indicate that schizophrenia patients h ave intrinsic defects in both activity and connectivity of PFC, and that these defects are specifically associated with impairments in cogniti ve abilities.Copyright © 2015 Wiley Periodicals, Inc.

Publication Type: Journal Article.

Research Support, Non-U.S. Gov’t.