Connectome-Guided Personalization of Optimal TDCS Intervention Selection in Alzheimer's Disease: A Modeling Study.

Overview

1. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Amsterdam 1081 HZ, The Netherlands
2. Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 HZ, The Netherlands
3. Department of Clinical Neurophysiology and MEG, Amsterdam UMC, Amsterdam 1081 HZ, The Netherlands
4. EQT Life Sciences Dementia Fund, Amsterdam 1071 DV, The Netherlands

Abstract

Transcranial direct current stimulation (tDCS) could reduce the neurophysiological effects in Alzheimer's disease (AD), but progress is hampered by variable outcomes across studies, likely related to both methodological and individual differences. We recently described a virtual brain network simulation method for optimizing tDCS interventions and now propose a method for further personalizing this approach. We now personalized the model for six female and four male biomarker-confirmed AD patients based on their brain structure and functional connectivity by using individual structural magnetic resonance imaging data and amplitude envelope correlation-based connectivity matrices extracted from magnetoencephalography (MEG) scans, respectively. We then assessed a set of previously established stimulation strategies based on their ability to improve relevant neurophysiological outcome parameters in each personalized model while undergoing AD damage. Personalized tDCS strategies were able to delay neurophysiological deterioration, but while the general model favored posterior anodal stimulation targeting the precuneus region, the personalized models favored frontal anodal stimulation targeting the dorsolateral prefrontal cortex region in 90% of the cases. This may be explained by higher connectivity levels of frontal regions in the personalized connectivity matrices, as anodal stimulation of highly connected regions produced more beneficial effects. In this methodological study, we propose several ways to improve personalized computational tDCS stimulation prediction modeling. We conclude that connectome-guided personalization of tDCS effects lead to different strategies with potentially better intervention outcomes. For external validation of this model-guided tDCS approach, model predictions are being tested in an ongoing clinical tDCS–MEG trial in AD patients.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

Code accessibility

As the data were generated using the graphical interface of the BrainWave software, there is no relevant code to be made available. However, the Brainwave software is made freely available at https://github.com/CornelisStam/BrainWave. The generated data have also been made available on a Zenodo repository at https://doi.org/10.5281/zenodo.14861689.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

• zenodo:14861689, at Zenodo; found in “Code accessibility”

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 4 keywords, 13 MeSH terms, 2 funders, 93 references.

Cite

This paper

Luppi, J. J., Koomen, A. P., Stam, C. J., Scheltens, P., & de Haan, W. (2026). Connectome-Guided Personalization of Optimal TDCS Intervention Selection in Alzheimer's Disease: A Modeling Study. eNeuro, 13(8), ENEURO.0407-25.2026. https://doi.org/10.1523/eneuro.0407-25.2026

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41598-026-45549-3

Effects of single-session anodal transcranial direct current stimulation (tDCS) on cognitive and motor performance in athletes and healthy adults: a systematic review and meta-analysis.

Journal: Scientific reports

In common: other, 4 references

[2] doi:10.1093/braincomms/fcag117

Connectome disruptions after hypoxic-ischaemic injury associate with consciousness disorder severity.

Journal: Brain communications

In common: structural MRI / diffusion, 4 references

[3] doi:10.1038/s41467-026-69866-3 [code]

Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology.

Journal: Nature communications

In common: Alzheimer's / dementia, 3 references

[4] doi:10.1002/hbm.70484 [code]

Frequency-Resolved Cortical Functional Connectivity Across the Adult Lifespan.

Journal: Human brain mapping

In common: MEG, 3 references

[5] doi:10.1038/s41598-026-56387-8 [code]

Alterations in topological and dynamical parameters correlate with disease biomarkers and neuropsychological scores in prodromic stages of dementia.

Journal: Scientific reports

In common: Alzheimer's / dementia, structural MRI / diffusion, 3 references

[6] doi:10.1371/journal.pcbi.1014022 [code]

Emergence of multifrequency activity in a laminar neural mass model.

Journal: PLoS computational biology

In common: Alzheimer's / dementia, 3 references

[7] doi:10.1162/imag.a.1109

Simultaneous tDCS-fMRI reveals limited and inconsistent changes in functional connectivity: Insights from a temporal dynamics study.

Journal: Imaging neuroscience (Cambridge, Mass.)

In common: other, 3 references

[8] doi:10.1007/s00429-025-03012-5 [code]

The neurophysiology of healthy and pathological aging: a comprehensive systematic review

Journal: n/a

In common: MEG, Alzheimer's / dementia, 2 references

[9] doi:10.1038/s41467-026-71961-4 [code]

Spatiotemporal asymmetries on brain energy landscape uncover system entrapment related to depression severity.

Journal: Nature communications

In common: structural MRI / diffusion, 3 references

[10] doi:10.1371/journal.pcbi.1014222 [code]

Neural population models for EEG: From Canonical models to alternative model structures.

Journal: PLoS computational biology

In common: 3 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.