Effective connectivity and pharmacological modulation in schizophrenia

Aside from the characteristic psychopathological symptoms, cognitive deficits, particular in the domains of working memory and executive functions, are a core feature of schizophrenia. Univariate statistical analyses have provided evidence that extended neuronal systems are subserving these cognitive functions. Schizophrenia has been conceptualized as a “dysconnection syndrome“ affecting the underlying neuronal circuitry.

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, the direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs.

The findings are suggesting that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of “cognitive dysmetria“ in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. Atypical antipsychotics appear to have beneficial effects on interhemispheric communication thereby presumably alleviating the effect of structural deficits as described in previous studies.

Schlösser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P (2003) Neuroimage, in press