Altered prefrontal activity and connectivity predict different cognitive deficits in schizophrenia.
BACKGROUND
Cognitive dysfunction is considered a core feature of schizophrenia, and impaired performances in episodic memory (EM) and executive function (EF) tasks are consistently reported in schizophrenia patients. Traditional fMRI and EEG studies have helped identifying brain areas, including the prefrontal cortex (PFC), involved in these tasks. However, it is unclear whether intrinsic defects in prefrontal function per se contribute to poor performance in schizophrenia, given the presence of confounds like reduced motivation and psychotic symptoms. 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 patients (N=20). Source modeling of TMS-evoked responses was performed, and measures of cortical activity (significant current density, SCD) and connectivity (significant current scattering, SCS) were computed. Patients with schizophrenia also performed Penn Word memory delayed (CPWd) and Penn Conditional Exclusion Test (PCET). CPWd evaluates EM and involves primarily PFC, whereas PCET reflects EF and implicates PFC with other brain regions.


RESULTS
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.


CONCLUSIONS
These findings indicate that schizophrenia patients have intrinsic defects in both activity and connectivity of PFC, and that these defects are specifically associated with impairments in cognitive abilities.
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.|Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Fabio
F
Ferrarelli
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Brady A
BA
Riedner
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Michael J
MJ
Peterson
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Giulio
G
Tononi
D000328:Adult; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology*; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
TMS; cognitive function; hd-EEG; prefrontal cortex; schizophrenia; source modeling