The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia

Abstract Background The two subtypes of primary progressive aphasia (PPA) associated with Frontotemporal Lobar Degeneration (FTLD)—non-fluent (nfvPPA) and semantic (svPPA)—have distinct structural and functional abnormalities. Transcranial direct current stimulation (tDCS) targets the language netwo...

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Main Authors: Sagarika Bhattacharjee, P. T. Sivakumar, Ganesan Venkatasubramanian, Kenichi Oishi, Kyrana Tsapkini, S. H. Annabel Chen, Brenda Rapp, John E. Desmond, T. N. Sathyaprabha, Kaviraja Udupa, Rajan Kashyap
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Alzheimer’s Research & Therapy
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Online Access:https://doi.org/10.1186/s13195-025-01737-3
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author Sagarika Bhattacharjee
P. T. Sivakumar
Ganesan Venkatasubramanian
Kenichi Oishi
Kyrana Tsapkini
S. H. Annabel Chen
Brenda Rapp
John E. Desmond
T. N. Sathyaprabha
Kaviraja Udupa
Rajan Kashyap
author_facet Sagarika Bhattacharjee
P. T. Sivakumar
Ganesan Venkatasubramanian
Kenichi Oishi
Kyrana Tsapkini
S. H. Annabel Chen
Brenda Rapp
John E. Desmond
T. N. Sathyaprabha
Kaviraja Udupa
Rajan Kashyap
author_sort Sagarika Bhattacharjee
collection DOAJ
description Abstract Background The two subtypes of primary progressive aphasia (PPA) associated with Frontotemporal Lobar Degeneration (FTLD)—non-fluent (nfvPPA) and semantic (svPPA)—have distinct structural and functional abnormalities. Transcranial direct current stimulation (tDCS) targets the language network to address deficits, yet a single, arbitrary montage is often applied despite pathophysiological differences. Since tDCS current distribution depends on brain structure and function, variant-specific montages are essential. This study presents a pathology-specific approach for tDCS montage selection, identifying the optimal montage for each PPA variant. Method T1-weighted and resting-state fMRI data from 38 healthy, 31 nfvPPA and 32 svPPA subjects were obtained. Grey matter volume and functional entropy were analysed across 116 brain regions. Patients and controls were compared to identify significant differences in atrophy and entropy. Electric-field modelling of three widely used dorsal, ventral, and frontal tDCS montages provided current intensity estimates in the language network. Canonical Correlation Analysis examined the relationship between current intensity, atrophy, and entropy. Results Structural and functional changes differed between the two PPA variants: nfvPPA showed left frontal atrophy and reduced entropy in the left parietal/cerebellar areas, while svPPA exhibited left temporal atrophy and reduced entropy in the left frontal and right temporal regions. Atrophy distribution primarily influenced tDCS current spread, determining montage suitability. In nfvPPA, the frontal montage showed a strong association between delivered current and grey mettwr volume of atrophied areas, whereas in svPPA, a similar pattern was observed for the ventral montage. Conclusion The study identifies the frontal montage as the most suitable for nfvPPA and the ventral montage for svPPA. This study highlights the importance of pathology-specific tDCS montage selection, emphasizing the need for variant-based modulation of the language network in PPA.
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spelling doaj-art-2d905ce06b9b46cf8da394b207c907fe2025-08-20T04:01:53ZengBMCAlzheimer’s Research & Therapy1758-91932025-07-0117111610.1186/s13195-025-01737-3The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasiaSagarika Bhattacharjee0P. T. Sivakumar1Ganesan Venkatasubramanian2Kenichi Oishi3Kyrana Tsapkini4S. H. Annabel Chen5Brenda Rapp6John E. Desmond7T. N. Sathyaprabha8Kaviraja Udupa9Rajan Kashyap10Department of Neurophysiology, NIMHANSDepartment of Psychiatry, NIMHANSDepartment of Psychiatry, NIMHANSThe Johns Hopkins University School of MedicineThe Johns Hopkins University School of MedicineDepartment of Psychology, Nanyang Technological UniversityDepartment of Cognitive Sciences, The Johns Hopkins UniversityThe Johns Hopkins University School of MedicineDepartment of Neurophysiology, NIMHANSDepartment of Neurophysiology, NIMHANSDepartment of Neuroimaging and Interventional Radiology, NIMHANSAbstract Background The two subtypes of primary progressive aphasia (PPA) associated with Frontotemporal Lobar Degeneration (FTLD)—non-fluent (nfvPPA) and semantic (svPPA)—have distinct structural and functional abnormalities. Transcranial direct current stimulation (tDCS) targets the language network to address deficits, yet a single, arbitrary montage is often applied despite pathophysiological differences. Since tDCS current distribution depends on brain structure and function, variant-specific montages are essential. This study presents a pathology-specific approach for tDCS montage selection, identifying the optimal montage for each PPA variant. Method T1-weighted and resting-state fMRI data from 38 healthy, 31 nfvPPA and 32 svPPA subjects were obtained. Grey matter volume and functional entropy were analysed across 116 brain regions. Patients and controls were compared to identify significant differences in atrophy and entropy. Electric-field modelling of three widely used dorsal, ventral, and frontal tDCS montages provided current intensity estimates in the language network. Canonical Correlation Analysis examined the relationship between current intensity, atrophy, and entropy. Results Structural and functional changes differed between the two PPA variants: nfvPPA showed left frontal atrophy and reduced entropy in the left parietal/cerebellar areas, while svPPA exhibited left temporal atrophy and reduced entropy in the left frontal and right temporal regions. Atrophy distribution primarily influenced tDCS current spread, determining montage suitability. In nfvPPA, the frontal montage showed a strong association between delivered current and grey mettwr volume of atrophied areas, whereas in svPPA, a similar pattern was observed for the ventral montage. Conclusion The study identifies the frontal montage as the most suitable for nfvPPA and the ventral montage for svPPA. This study highlights the importance of pathology-specific tDCS montage selection, emphasizing the need for variant-based modulation of the language network in PPA.https://doi.org/10.1186/s13195-025-01737-3PathologySpecific tDCS, Primary progressive aphasiaSemantic and nonFluent, structural atrophy, functional entropy, currentAtrophyEntropy relationship
spellingShingle Sagarika Bhattacharjee
P. T. Sivakumar
Ganesan Venkatasubramanian
Kenichi Oishi
Kyrana Tsapkini
S. H. Annabel Chen
Brenda Rapp
John E. Desmond
T. N. Sathyaprabha
Kaviraja Udupa
Rajan Kashyap
The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
Alzheimer’s Research & Therapy
Pathology
Specific tDCS, Primary progressive aphasia
Semantic and non
Fluent, structural atrophy, functional entropy, current
Atrophy
Entropy relationship
title The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
title_full The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
title_fullStr The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
title_full_unstemmed The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
title_short The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia
title_sort role of structural and functional parameters in designing pathology specific tdcs protocols for primary progressive aphasia
topic Pathology
Specific tDCS, Primary progressive aphasia
Semantic and non
Fluent, structural atrophy, functional entropy, current
Atrophy
Entropy relationship
url https://doi.org/10.1186/s13195-025-01737-3
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