Comparing local brain activity and distant functional connectivity in transgender women compared to cisgender controls

To date, the knowledge about the neurobiological mechanisms associated with transgender populations, especially transgender women (TW), remains limited and lacks consensus. This study aims to fill such gaps using the functional magnetic resonance imaging (fMRI) method. Resting-state fMRI data was obtained from 16 TW, 16 cisgender men (CM), and 16 cisgender women (CW). Measures of local brain activity and distant functional connectivity (FC) were compared among groups. Several corresponding dynamic measures were also explored based on the assumption of fluctuating brain functional organizations over time. For local brain activity, TW showed higher amplitude of low-frequency fluctuation within the cerebellum, precentral gyrus, and thalamus, as well as lower regional homogeneity in the precuneus than cisgender participants. For FC measures, TW showed weaker FCs mainly involving the ventral attention and sensorimotor networks, as well as lower local efficiency than cisgender participants. In most of these measures, CM were intermediate among the three groups (i.e., TW < CM < CW, or TW > CM > CW). Our results suggest that TW have distinct patterns of brain function compared with cisgender people, while they are more aligned with those of CM (their sex assigned at birth) rather than CW.