572. Effects of 10Hz transcranial focused ultrasound stimulation of the posterior cingulate cortex on working memory performance – initial findings

Abstract

Abstract Background Working memory impairments are common across various neuropsychiatric disorders (1). The posterior cingulate cortex (PCC) plays a central role in working memory function (2, 3). Low intensity transcranial focused ultrasound stimulation (TUS) offers a method to non-invasively modulate neuronal activity of deep brain structures. Although TUS of the PCC has been shown to induce neurochemical and functional connectivity changes (4), it remains unclear, whether the stimulation affects working memory performance. Aims & Objectives This work aims to determine whether TUS targeting the PCC alters working memory performance. Method In a randomized, double-blind, sham-controlled parallel-group design, 16 healthy participants (8 females, mean age: 22.2 ± 2.1 years) received active TUS (n=9) or sham (n=7). Neuronavigated TUS (500 kHz) targeted the PCC (MNI coordinate x=-5, y=-35, z=35). The protocol (10Hz PRF, 5% duty cycle, 10 pause-interleaved blocks of 30s; 10min in total) was applied with a free field Isppa of 30W/cm2. Acoustic simulations estimated a mean in situ Isppa: 4.77 ± 0.94W/cm2, adhering to ITRUSST safety standards (5). Sham consisted of an auditory control to mimic TUS audibility. Working memory was assessed using the 2-back task from the TAP (6) pre- and post-intervention (interval≈60min). Performance outcomes were Biscores, combining accuracy and reaction time (ZAccuracy–ZRT) and accuracy improvement, defined as the absolute error reduction. Intervention effects were analyzed using Mann Whitney U tests (α=0.05) conducted in R (7). Results Regarding global performance (Biscores), the active group showed a descriptive increase (mean change: +0.78), whereas the sham group exhibited a decline (-0.19). However, this difference was not statistically significant (p=0.29). Regarding specific improvement (accuracy), the active group showed significantly greater error reduction compared to sham (U=51, p=0.035). Discussion & Conclusions Active TUS at the PCC was associated with improved response accuracy, however, the observed improvement of global working memory performance was not statistically significant. Thus, although effects of TUS on working memory performance appear to be possible, the data are inconclusive. A major limitation is the small sample size of this pilot project. Future, adequately powered studies will be required to clarify whether TUS of the PCC holds potential for improving working memory function, specifically in neuropsychiatric patients.