Efficacy of Cortical-Hippocampal Target Intermittent Theta Burst Stimulation (iTBS) on Associative Memory of Schizophrenia: A Double-Blind, Randomized Sham-Controlled Trial

Objective: The objective of our study was to evaluate whether intermittent theta burst stimulation(iTBS) applied to the regions with the strongest cortico-hippocampal connectivity within the lateral parietal cortical (LPC) or dorsolateral prefrontal cortical (DLPFC) areas in individuals with schizophrenia could enhance associative memory. Methods: We randomized 96 participants with schizophrenia to receive either active iTBS applied to the right DLPFC, left LPC or sham iTBS for 20 days. Clinical and cognitive assessments were performed at baseline and at the end of treatment. The primary outcome was change in associative memory. The secondary outcome was change in other cognitive functions and psychiatric symptoms. Results: In comparison to the sham group, iTBS targeting the right DLPFC or left LPC in schizophrenia did not yield significant improvements in auditory-auditory associative memory (F=1.27, p=0.294), auditory-visual associative memory (F=0.49, p=0.617), or visual-visual associative memory (F=1.094, p=0.347). Furthermore, after adjusting for variables such as education, disease duration, and negative symptoms, no significant changes were observed in any of these three memory domains. Conclusion: Although our study suggests that iTBS applied to the cortical-hippocampal did not lead to a significant change in associative memory. However, further investigation combining hippocampal-targeted iTBS with functional magnetic resonance imaging (fMRI) is warranted to elucidate the regulatory effects of iTBS on hippocampal function. Trial Registration: clinicaltrials.gov NCT03608462.