Fronto-thalamic dysconnectivity and cognitive control in schizophrenia

Abstract

Introduction

Several lines of evidence suggest that cognitive deficits represent a core feature of schizophrenia.

Objectives

The concept of “cognitive dysmetria” has been introduced to characterize disintegration at the system level of frontal-thalamic-cerebellar circuitry which has been regarded as a key network for a wide range of neuropsychological symptoms in schizophrenia.

Aims

The present multimodal study aimed at investigating effective and structural connectivity of the frontal-thalamic circuitry in schizophrenia.

Methods

Univariate fMRI data analysis and effective connectivity analysis using dynamic causal modeling (DCM) were combined to examine cognitive control processes in 40 patients with schizophrenia and 40 matched healthy controls. BOLD signal and parameters of effective connectivity were related to parameters of corresponding white matter integrity assessed with diffusion tensor imaging (DTI).

Results

In the DTI analysis, significantly decreased fractional anisotropy (FA) was detected in patients in the right anterior limb of the internal capsule (ALIC), the right thalamus and the right corpus callosum. During Stroop task performance patients demonstrated significantly lower activation relative to healthy controls in a predominantly right lateralized frontal-thalamic-cerebellar network. An abnormal effective connectivity was observed in the right lateralized connections between thalamus, anterior cingulate and dorsolateral prefrontal cortex. FA in the right ALIC was significantly correlated with the fronto-thalamic BOLD signal, effective connectivity and cognitive performance in patients.

Conclusions

Present data provide evidence for the notion of a structural and functional defect in the prefrontal-thalamic-cerebellar circuitry, which seems to be the basis of the cognitive control deficits in schizophrenia.

Disclosure of interest

The authors have not supplied their declaration of competing interest.