Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous...

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Main Authors: Marco Muccio, Giuseppina Pilloni, Lillian Walton Masters, Peidong He, Lauren Krupp, Abhishek Datta, Marom Bikson, Leigh Charvet, Yulin Ge
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Bioengineering
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Online Access:https://www.mdpi.com/2306-5354/12/6/672
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author Marco Muccio
Giuseppina Pilloni
Lillian Walton Masters
Peidong He
Lauren Krupp
Abhishek Datta
Marom Bikson
Leigh Charvet
Yulin Ge
author_facet Marco Muccio
Giuseppina Pilloni
Lillian Walton Masters
Peidong He
Lauren Krupp
Abhishek Datta
Marom Bikson
Leigh Charvet
Yulin Ge
author_sort Marco Muccio
collection DOAJ
description Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills.
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spelling doaj-art-fd144f21c5bc408d8eb75432a929db722025-08-20T03:32:31ZengMDPI AGBioengineering2306-53542025-06-0112667210.3390/bioengineering12060672Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI StudyMarco Muccio0Giuseppina Pilloni1Lillian Walton Masters2Peidong He3Lauren Krupp4Abhishek Datta5Marom Bikson6Leigh Charvet7Yulin Ge8Department of Radiology, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Neurology, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Neurology, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Radiology, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Neurology, NYU Grossman School of Medicine, New York, NY 10016, USAResearch and Development, Soterix Medical, Inc., Woodbridge, NJ 07095, USADepartment of Biomedical Engineering, City College of New York, New York, NY 10031, USADepartment of Neurology, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Radiology, NYU Grossman School of Medicine, New York, NY 10016, USATranscranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills.https://www.mdpi.com/2306-5354/12/6/672transcranial direct current stimulation (tDCS)multiple sclerosis (MS)healthy controlsresting-state functional MRI (rs-fMRI)neuromodulationfractional amplitude of low-frequency fluctuations (fALFFs)
spellingShingle Marco Muccio
Giuseppina Pilloni
Lillian Walton Masters
Peidong He
Lauren Krupp
Abhishek Datta
Marom Bikson
Leigh Charvet
Yulin Ge
Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
Bioengineering
transcranial direct current stimulation (tDCS)
multiple sclerosis (MS)
healthy controls
resting-state functional MRI (rs-fMRI)
neuromodulation
fractional amplitude of low-frequency fluctuations (fALFFs)
title Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
title_full Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
title_fullStr Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
title_full_unstemmed Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
title_short Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
title_sort resting state activity changes induced by tdcs in ms patients and healthy controls a simultaneous tdcs rs fmri study
topic transcranial direct current stimulation (tDCS)
multiple sclerosis (MS)
healthy controls
resting-state functional MRI (rs-fMRI)
neuromodulation
fractional amplitude of low-frequency fluctuations (fALFFs)
url https://www.mdpi.com/2306-5354/12/6/672
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