Abstract
BACKGROUND: Deficient mirror neuron system (MNS)-activity is associated with social cognition deficits in schizophrenia. However, it is not known how socio-emotional contexts modulate the MNS-response. In a Transcranial Magnetic Stimulation (TMS)-experiment, we aimed to compare putative MNS-responses to action observation stimuli with and without a context, in patients with schizophrenia and healthy subjects. METHOD: TMS-evoked motor cortical reactivity was measured by single and paired [short interval intracortical inhibition (SICI) and facilitation (ICF)] pulse-paradigms in schizophrenia patients (n = 39) and healthy subjects (n = 28) while they observed three experimental-blocks: a static image, a neutral hand action (NA) and a context-based hand action (CA). The degree of cortical reactivity facilitation with the two action observation blocks, relative to the static block provided indirect measures of premotor MNS-activity. A subset of patients (n = 31) also underwent comprehensive social cognition assessments. RESULTS: RMANOVA demonstrated significantly higher cortical reactivity during the CA-block in both groups (all TMS-paradigms); albeit significantly less pronounced in patients (SICI and ICF paradigms). MNS-activity during the CA-block was significantly higher compared to that during the NA-block in both groups (all TMS-paradigms), but significantly less pronounced in patients (SICI and single-pulse paradigms). MNS-activity during the CA-block measured by the ICF paradigm was positively correlated with social cognition performance. CONCLUSION: Providing a context to the action modulates MNS-activity. This modulation is diminished in schizophrenia patients, suggestive of a diminished sensorimotor associative learning process. This novel, ecologically valid paradigm to tap into the MNS may serve as a neuro-marker of social cognition performance in schizophrenia.