Intermittent theta burst stimulation for negative symptoms in schizophrenia patients with moderate to severe cognitive impairment: A randomized controlled trial

Aims This study aims to assess the therapeutic effects of intermittent theta burst stimulation (iTBS) targeting the bilateral dorsomedial prefrontal cortex (DMPFC) on negative symptoms in patients with schizophrenia, utilizing functional near‐infrared spectroscopy for evaluation. Methods Thirty‐five schizophrenia patients with negative symptoms and moderate to severe cognitive impairment were randomly assigned to a treatment group ( n = 18) or a control group ( n = 17). The treatment group received iTBS via bilateral DMPFC. Negative symptoms, cognitive function, emotional state, and social function were assessed using Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Montreal Cognitive Assessment (MoCA), Calgary Depression Scale for Schizophrenia (CDSS), and Social Dysfunction Screening Questionnaire (SDSS) scales at pretreatment, posttreatment, and follow‐up at 4, 8, and 12 weeks. Brain activation in regions of interest (ROIs) was evaluated through verbal fluency tasks. Results Prior to treatment there was no significant difference in the two groups. After 20 iTBS sessions, a significant difference was observed in SANS total score, its related subscales, PANSS total score, and PANSS‐negative symptoms (all P < 0.05). The group‐by‐time interaction showed statistical significance, indicating improvements in negative symptoms and related dimensions over time, with therapeutic effects persisting for at least 8 weeks posttreatment. Prior to treatment, there were no significant differences in activation across all ROIs between the two groups. Posttreatment, the activation of right inferior frontal gyrus ( t = 2.19, P = 0.036) and right frontal eye field ( t = 2.14, P = 0.04) in the treatment group was significantly higher than in the control group. Conclusions iTBS stimulation of bilateral DMPFC demonstrates therapeutic effects in improving negative symptoms in schizophrenia patients, and this treatment approach has the potential to enhance activation within the prefrontal cortex.