Pharmacological Modulation of Cognitive Functions: Studies with fMRI

There is ample evidence that normal cognitive and emotional information processing is functionally dependent on the concerted activity of different interacting neurotransmitter systems. In a series of studies, we employed acute pharmacological challenge paradigms and subchronic pharmacological interventions in order to elucidate GABAergic and dopaminergic effects on functional brain imaging patterns subserving short-term working memory, learning processes and prediction uncertainty. An acute lorazepam challenge was associated with decreased cortical and subcortical activity during a 2-back working memory task. For alcohol-dependent patients, a blunted dopaminergic cerebellar response could be observed suggesting altered cerebellar GABAergic setpoints. On the other hand, fMRI activation during a prediction uncertainty task was found to be pronounced in the DLPFC after a dopaminergic methylphenidate challenge. Additionally, atypical antipsychotic drugs with a potential to enhance dopaminergic functions were associated with altered information processing not only in the PFC but also in an entire cortical-subcortical cerebellar circuitry in schizophrenic patients. Taken together, these findings indicate the regulatory capacity of both GABAergic and dopaminergic mechanisms and the existence of propagated effects involving changes in effective connectivity between segregated brain areas. Functional MRI appears to be a suitable tool to monitor the restoration of normal activation patterns during psychopharmacological interventions.