Non-invasive neuromodulation of the right temporoparietal junction using theta-burst stimulation in functional neurological disorder

Janine Bühler; Samantha Weber; Serafeim Loukas; Sebastian Walther; Selma Aybek

doi:10.1136/bmjno-2023-000525

Non-invasive neuromodulation of the right temporoparietal junction using theta-burst stimulation in functional neurological disorder

BMJ Neurol Open. 2024 Feb 14;6(1):e000525. doi: 10.1136/bmjno-2023-000525. eCollection 2024.

Authors

Janine Bühler^{1

2}, Samantha Weber¹, Serafeim Loukas^{1

3}, Sebastian Walther⁴, Selma Aybek^{1

5}

Affiliations

¹ Psychosomatic Medicine, Department of Neurology, Inselspital University Hospital Bern, Bern, Switzerland.
² Graduate School for Health Sciences (GHS), University of Bern, Bern, Switzerland.
³ Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
⁴ University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
⁵ Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.

Abstract

Background: Disrupted sense of agency (SoA)-the sense of being the agent of one's own actions-has been demonstrated in patients with functional neurological disorder (FND), and a key area of the corresponding neuronal network is the right temporoparietal junction (rTPJ). Several functional MRI (fMRI) studies have found hypoactivation as well as hyperactivation of the rTPJ in FND. In a proof-of-concept study, we tested whether repetitive transcranial magnetic stimulation (rTMS) over the rTPJ could restore this aberrant activity.

Methods: In a randomised, crossover, single-blinded, sham-controlled study design, theta-burst stimulation (tb-rTMS) was applied over the rTPJ in 23 patients with FND and 19 healthy controls (HC), with each participant undergoing three stimulatory visits (inhibitory continuous TBS (cTBS), excitatory intermittent TBS (iTBS) and sham). During fMRI, participants played a visuomotor task artificially reducing their SoA (manipulated agency, MA), repeated after each neurostimulation. We compared brain activity and behavioural SoA as primary outcomes before and after tb-rTMS and investigated the feasibility of tb-rTMS over the rTPJ in FND as secondary outcome.

Results: At baseline, patients showed decreased accuracy in detecting reduced agency compared with controls (p<0.001), paralleled by lower brain activation in the rTPJ during MA (p=0.037, volume of interest). A region of interest analysis on the rTPJ showed no effect of the sham condition in FND or HC (p=0.917; p=0.375) but revealed a significant effect of stimulation protocol (cTBS/iTBS, p=0.037) in patients with FND, with the excitatory protocol increasing the blood-oxygen-level-dependent (BOLD) signal, whereas this effect was not found in HC. In neither group, a behavioural effect of tb-rTMS was observed.

Conclusion: Aberrant processing of agency in FND was confirmed at baseline, reflected in behavioural outcome and reduced activity in the rTPJ. Tb-rTMS over this key region elicited neuronal changes in patients, paving ways for future studies exploring TMS as neurobiologically informed intervention to restore SoA in FND. We critically discuss methodological intricacies and outline further steps in this research line.

Keywords: CONVERSION DISORDER; FUNCTIONAL IMAGING; FUNCTIONAL NEUROLOGICAL DISORDER; MAGNETIC STIMULATION; NEUROPSYCHIATRY.