Cortico-cortical paired associative stimulation of inhibitory control networks in borderline personality disorder

Impaired inhibitory control is a core feature of borderline personality disorder (BPD) and a key driver of impulsive behaviors, particularly in emotionally salient contexts. Dysfunction within fronto-cortical networks, including the inferior frontal cortex (IFC) and pre-supplementary motor area (pre-SMA), has been implicated, yet causal evidence remains scarce. We used cortico-cortical paired associative stimulation (ccPAS) to target IFC-pre-SMA connectivity and test its impact on inhibitory control in BPD. In a randomized, double-blind, controlled study, 40 individuals with BPD received a single ccPAS session with either a 4-ms (active) or 100-ms (control) interstimulus interval (ISI). The primary outcome was the change in stop-signal reaction time (SSRT) during an affective stop-signal task. Baseline measures included self-reported impulsivity (UPPS-P), short-interval intracortical inhibition (SICI), and SSRT. ccPAS significantly reduced SSRT, indicating improved response inhibition, with no difference between ISI conditions. SICI was not associated with SSRT or UPPS-P scores. In contrast, SSRT correlated with positive urgency, suggesting a specific link between inhibitory performance and affect-driven impulsivity. These findings suggest that dual-site IFC-pre-SMA stimulation may improve inhibitory control in BPD. However, the absence of ISI-specific effects precludes attributing this improvement to pathway-specific modulation and may reflect mechanisms beyond canonical spike-timing-dependent plasticity, possibly involving broader network engagement. The dissociation between SICI and behavioral or trait measures further indicates that local motor cortical inhibition does not capture higher-order affective control processes. Together, this study supports the potential of dual-site stimulation approaches for impulsivity in BPD, while highlighting the need for further work to clarify the network-level mechanisms involved.