SEX DIFFERENCES IN BRAIN EXCITABILITY REVEALED BY CONCURRENT ITBS/FNIRS

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (lDLPFC) is a demonstrably efficacious therapy for various symptoms of psychiatric disorders (Kan et al., 2023b). Recent evidence indicates sex differences is an imperative factor in optimizing pharmacotherapeutic antidepressant treatments (Wilson et al., 2023). However, sex differences in rTMS over lDLPFC and the underlying neural mechanisms remain unclear. Aims & Objectives Here, we investigated whether the real-time neural response to intermittent theta- burst stimulation (iTBS) differs between men and women, and which mechanisms may mediate these differences. Methods In a series of experiments, we investigated potential sex differences in healthy, right-handed participants. We measured prefrontal hemoglobin concentrations during rest, during cognitive tasks (N- back and verbal fluency), as well as during concurrent brain stimulation with iTBS using functional near- infrared spectroscopy (fNIRS). We capitalized on a concurrent iTBS/fNIRS setup developed in our lab that allows measuring the instantaneous neuronal response of iTBS over lDLPFC (Kan et al., 2023a). A figure- of-eight shaped cooling coil (Cool-B65) and the MagPro magnetic stimulator (MagVenture) were used for stimulation Results We found (1) a biological sex difference in absolute hemoglobin concentrations in the left DLPFC (p<0.001, n=66, 38 females); (2) that this sex difference is amplified by iTBS (p=0.001, n=56, 23 females) but not by cognitive tasks (both p>=0.05, n=71, 46 females); and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity (p=0.004, n=24, 12 females, see Figure 1). Discussion & Conclusion Our results indicate that sex-specific effects of stimulation-induced prefrontal excitability are an important aspect to consider in the advancement of brain stimulation protocols towards precision psychiatry (Mauvais-Jarvis et al., 2020). References KAN, R. L. D., LIN, T. T. Z., ZHANG, B. B. B., GIRON, C. G., JIN, M., QIN, P. P. I., XIA, A. W. L., CHAN, S. K. W., CHAU, B. K. H. &KRANZ, G. S. 2023a. Moderators of stimulation-induced neural excitability in the left DLPFC: A concurrent iTBS/fNIRS case study. Brain Stimul. KAN, R. L. D., PADBERG, F., GIRON, C. G., LIN, T. T. Z., ZHANG, B. B. B., BRUNONI, A. R. &KRANZ, G. S. 2023b. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta- analysis. Lancet Psychiatry, 10, 252-259. MAUVAIS-JARVIS, F., BAIREY MERZ, N., BARNES, P. J., BRINTON, R. D., CARRERO, J. J., DEMEO, D. L., DE VRIES, G. J., EPPERSON, C. N., GOVINDAN, R., KLEIN, S. L., LONARDO, A., MAKI, P. M., MCCULLOUGH, L. D., REGITZ-ZAGROSEK, V., REGENSTEINER, J. G., RUBIN, J. B., SANDBERG, K. &SUZUKI, A. 2020. Sex and gender: modifiers of health, disease, and medicine. Lancet, 396, 565-582. WILSON, J. D., GERLACH, A. R., KARIM, H. T., AIZENSTEIN, H. J. &ANDREESCU, C. 2023. Sex matters: acute functional connectivity changes as markers of remission in late-life depression differ by sex. Mol Psychiatry.