Transdiagnostic investigation into the relationship between mirror neuron system activity, echo-phenomena, and theory of mind in major psychoses

The association between social cognition and putative mirror neuron system (MNS)-activity in major psychoses might be contingent upon frontal dysregulation. We used a transdiagnostic ecological approach to enrich a specific behavioral phenotype (echophenomena or hyper-imitative states) across clinical diagnoses (mania and schizophrenia) to compare behavioral and physiological markers of social cognition and frontal disinhibition. We examined 114 participants with schizophrenia (N = 53) and mania (N = 61) for the presence and severity of echo-phenomena (echopraxia, incidental, and induced echolalia) using an ecological paradigm to simulate real-life social communication. Symptom severity, frontal release reflexes, and theory of mind performance were also assessed. In a proportion of these participants with (N = 20) and without (N = 20) echo-phenomena, we compared motor resonance (motor evoked potential facilitation during action observation compared to static image viewing) and cortical silent period (CSP) as putative markers of MNS-activity and frontal disinhibition, respectively, using Transcranial Magnetic Stimulation. While the prevalence of echo-phenomena was similar between mania and schizophrenia, incidental echolalia was more severe in mania. Participants with echo-phenomena (compared to those without) had significantly greater motor resonance with singlepulse (not with paired-pulse) stimuli, poorer theory of mind scores, higher frontal release reflexes but similar CSP, and greater symptom severity. None of these parameters significantly differed between participants with mania and schizophrenia. We observed relatively better phenotypic and neurophysiological characterization of major psychoses by categorizing participants based on the presence of echophenomena than clinical diagnoses. Higher putative MNS-activity was associated with poorer theory of mind in a hyper-imitative behavioral state.