SEX DIFFERENCES IN BRAIN EXCITABILITY REVEALED BY CONCURRENT ITBS/FNIRS
Authors: Kan *Rebecca Laidi , Zhang Bella B B , Lin Tim T Z , Tang Alvin H P , Li Ami S M , Xia Adam W L , Qin Penny P I , Jin Minxia , Fong Kenneth N K , Becker Benjamin , Yau Suk-Yu , Kranz Georg S 
Published: February 2025

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&lt;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&gt;=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
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