Accelerated DMN-targeted cTBS improves processing speed deficits in schizophrenia

Cognitive deficits are a leading cause of disability in schizophrenia and are linked to poor functional outcomes. There are no first line treatments for these deficits, and their neural basis is poorly understood. While schizophrenia is associated with widespread cognitive deficits, information processing speed is most profoundly impaired. Processing speed deficits have been associated with hyperconnectivity in the Default Mode Network (DMN). We therefore tested if modulating DMN connectivity with single or multiple sessions of transcranial magnetic stimulation (TMS) applied to an individualized DMN target would affect processing speed. In the first study, 10 individuals with schizophrenia received single TMS sessions and underwent resting-state neuroimaging and processing speed assessment (Brief Assessment of Cognition in Schizophrenia digit symbol coding) acutely before and after each session. These sessions included excitatory (intermittent theta burst stimulation, iTBS); inhibitory (continuous theta burst stimulation, cTBS); and sham stimulation sessions. In the second study, 29 individuals (17 schizophrenia, 12 non-psychosis controls) received 5 accelerated sessions of cTBS with resting-state neuroimaging and processing speed assessment before and after the course of TMS sessions. In the accelerated, multi-session DMN-targeted TMS trial, cTBS improved processing speed in the schizophrenia group (p = 0.0124). In individuals with schizophrenia, reduction in DMN connectivity was linked to improvement in processing speed (p = 0.021). These changes were dependent on age, where younger participants experienced greater processing speed improvements than older participants (p = 0.006). In sum, personalized network targeted TMS may be a novel method for reducing cognitive impairment associated with schizophrenia.