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.

The authors would like to express their gratitude to Julie Tisserand for her help with data collection. The study was funded by the Scientific Research Council from Le Vinatier, Psychiatrie Universitaire Lyon Métropole (#PRVP07), Bron, France. Le Vinatier, Psychiatrie Universitaire Lyon Métropole, F-69500, Bron, France Nadine Barakat, Jérôme Brunelin, Emmanuel Poulet & Cécilia Neige Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, PSYR2, F-69500, Bron, France Department of Psychiatry and Addiction, University of Montreal, Quebec, Canada CIUSSS de l’Est-de-l’Île-de-Montréal, Quebec, Canada Research Center of the Montreal University Institute for Mental Health, Quebec, Canada Wafae Chinoune, Erika Abrial & Emmanuel Poulet ADDIPSY, Santé Basque Développement Group, Addictology and Psychiatry Outpatient Center, 69007, Lyon, France Centre de Recherche en Epidémiologie et Santé des Populations, DevPsy, INSERM, UVSQ, Université Paris-Saclay, 94807, Villejuif, France The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This study was approved by an ethics committee (CPP Ile de France X 15-2023 on June 6, 2023; ANSM registration number 2023-A00772-43) and was conducted in accordance with the recommendations provided in the current version of the Declaration of Helsinki. All participants gave their written informed consent before their inclusion in the study. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.