Enhancing Social Cognition in Mild Cognitive Impairment with Non-Invasive Brain Stimulation: A Randomized Clinical Trial

Background The effectiveness of non-invasive neuromodulation to improve social cognition (SC) in neurological disorders remains unclear. However, repetitive transcranial magnetic stimulation (rTMS) shows promise for treating cognitive abnormalities by promoting neuroplasticity. Objective In this randomized, double-blind, sham-controlled study, we investigated the effects of high-frequency rTMS on the medial prefrontal cortex (mPFC) and right temporal parietal junction (rTPJ) in patients with mild cognitive impairment (MCI) to enhance SC abilities and other cognitive and functional abilities related to the stimulated network, and their maintenance effects post-treatment. Methods Twenty-four MCI patients were assigned to 2 groups: a Real-Real group (RR-Gr) that received 4 weeks of rTMS, and a Sham-Real group (SR-Gr) that received 2 weeks of sham stimulation followed by 2 weeks of real rTMS. All subjects underwent cognitive/functional assessments at baseline, week 2, and week 4 of the treatment, and 8 weeks post-intervention (12 weeks). Results After 2 weeks of treatment, the RR-Gr improved in empathy performance ( P < .001), emotion-recognition ( P < .001), social-behavior (SB) ( P = .04), and executive function ( P = .014). Following 4 weeks of rTMS, emotion-recognition improved further, and the benefits persisted at follow-up observation (all P s < .001). In RR-Gr, patients with higher education exhibited more significant improvements in SB abilities ( P = .032). Both groups also improved attention, mobility, and quality of life over time ( P range :<.001-.02). Conclusions Excitatory rTMS treatment targeting 2 key social brain regions (mPFC and rTPJ) shows promise as a sustained intervention to improve SC and associated cognitive functions in the MCI population. Trial registration ClinicalTrials.gov ID: NCT04490616