Intermittent theta burst stimulation improved visual-spatial working memory in treatment-resistant schizophrenia: A pilot study

Visual-spatial working memory (vsWM) impairment in treatment-resistant schizophrenia (TRS) currently has no satisfactory treatment. Our study aimed to improve vsWM function in TRS through intermittent theta burst stimulation (iTBS) using neuronavigation equipment to target the left dorsolateral prefrontal cortex. TRS patients (n = 59) were randomly allocated to receive iTBS (n = 33) or a sham treatment (n = 26) over 2 weeks. The participants including TRS patients and healthy controls (HCs) performed the vsWM n-back task, and TRS patients' neuroimaging data were acquired before and after treatment. All patients also underwent a battery of symptom measures to assess the severity of illness. The main outcome measure was the accuracy (ACC) of n-back target responses, particularly 3-back ACC. The iTBS group showed considerable improvement in n-back ACC compared to the sham group, especially 3-back ACC. After iTBS, performance on the n-back task was comparable to that of HCs. The interaction (group × time) results showed increased fractional amplitude of low frequency fluctuations (fALFF) in the right occipital areas and decreased fALFF in the right precuneus. However, there was a negative correlation between the 3-back ACC and improved clinical symptoms scores. Improvements in 3-back ACC were positively correlated with activity in the right visual cortex. Our study suggested that 2 weeks of iTBS intervention may be a novel, efficacious treatment for vsWM deficits in TRS, which can modulate the activity of local brain regions. iTBS can provide a solution for clinical treatment of TRS and may help patients approach normalcy.