Increasing target engagement via customized electrode positioning for personalized transcranial electrical stimulation: A biophysical modeling study

Griffin Rodgers; Mahyar Joodaki; Alois Hopf; Emiliano Santarnecchi; Raphael Guzman; Bert Müller; Bekim Osmani

doi:10.1016/j.neuroimage.2025.121206

Increasing target engagement via customized electrode positioning for personalized transcranial electrical stimulation: A biophysical modeling study

Neuroimage. 2025 May 1:311:121206. doi: 10.1016/j.neuroimage.2025.121206. Epub 2025 Apr 12.

Authors

Griffin Rodgers¹, Mahyar Joodaki², Alois Hopf³, Emiliano Santarnecchi⁴, Raphael Guzman⁵, Bert Müller⁶, Bekim Osmani¹

Affiliations

¹ Bottneuro AG, Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland.
² Bottneuro AG, Basel, Switzerland.
³ Bottneuro AG, Basel, Switzerland. Electronic address: alois.hopf@bottneuro.ch.
⁴ Precision Neuroscience and Neuromodulation Program, Gordon Center for Medical Imaging Massachusetts General Hospital, Harvard Medical School, Boston, USA; Department of Neurology, Radiology & Psychiatry Massachusetts General Hospital, Boston, USA.
⁵ Department of Neurosurgery, University Hospital and University Children's Hospital Basel, Basel, Switzerland.
⁶ Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland; Department of Clinical Research, University Hospital Basel, Basel, Switzerland.

PMID: 40228684
DOI: 10.1016/j.neuroimage.2025.121206

Abstract

Background: Transcranial electric stimulation (TES) is a non-invasive neuromodulation technique with therapeutic potential for diverse neurological disorders including Alzheimer's disease. Conventional TES montages with stimulation electrodes in standardized positions suffer from highly varying electric fields across subjects due to variable anatomy. Biophysical modelling using individual's brain imaging has thus become popular for montage planning but may be limited by fixed scalp electrode locations.

Objective: Here, we explore the potential benefits of flexible electrode positioning with 3D-printed neurostimulator caps.

Methods: We modeled 10 healthy subjects and simulated montages targeting the left angular gyrus, which is relevant for restoring memory functions impaired by Alzheimer's disease. Using quantitative metrics and visual inspection, we benchmark montages with flexible electrode placement against well-established montage selection approaches.

Results: Personalized montages optimized with flexible electrode positioning provided tunable intensity and control over the focality-intensity trade-off, outperforming conventional montages across the range of achievable target intensities. Compared to montages optimized on a reference model, personalized optimization significantly reduced variance of the stimulation intensity in the target. Finally, increasing available electrode positions from 32 to around 86 significantly increased target engagement across a range of target intensities and current limits.

Conclusions: In summary, we provide an in silico proof-of-concept that digitally designed and 3D-printed TES caps with flexible electrode positioning can increase target engagement with precise and tunable control of applied dose to a cortical target. This is of interest for stimulation of brain networks such as the default mode network with spatially proximate correlated and anti-correlated cortical nodes.

Keywords: 3D-printing; Biophysical modeling; Electrode positioning; Target engagement; Transcranial electrical stimulation.

MeSH terms

Adult
Electrodes
Female
Humans
Male
Models, Neurological*
Parietal Lobe* / physiology
Printing, Three-Dimensional
Transcranial Direct Current Stimulation* / instrumentation
Transcranial Direct Current Stimulation* / methods