Neural mechanisms of proactive and reactive inhibitory control : Studies in healthy volunteers and schizophrenia patients

Abstract

The neural underpinnings of our ability to restrain actions in advance (i.e. proactive inhibition) and stop actions in reaction to some event (i.e. reactive inhibition) remain largely unknown. In this thesis we used neuroimaging (functional magnetic resonance imaging, fMRI) and brain stimulation (transcranial magnetic stimulation, TMS) to explore the mechanisms underlying proactive and reactive inhibition in the healthy brain and the brain affected by schizophrenia. In particular, we focused on how three brain regions – the right inferior frontal cortex (rIFC), the supplementary motor complex (SMC), and the striatum – interact to exert proactive and reactive inhibition over the primary motor cortex (M1). There are three main findings. First, the SMC and the striatum appear to play a role in both proactive and reactive inhibition, whereas the rIFC seems to be involved in reactive inhibition only. Second, during reactive inhibition, the rIFC appears to exert control over M1 via the SMC and the striatum. Third, patients with schizophrenia (as well as their unaffected siblings) are impaired in proactive inhibition, whereas reactive inhibition seems to be spared. Impaired proactive inhibition in schizophrenia is associated with reduced frontostriatal activation and poor working memory. Together, these findings provide insight into the mechanisms at play in behavioral control, highlighting the importance of frontostriatal pathways in restraining and stopping actions.