Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 19;12(6):672.
doi: 10.3390/bioengineering12060672.

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

Marco Muccio  1 , Giuseppina Pilloni  2 , Lillian Walton Masters  2 , Peidong He  1 , Lauren Krupp  2 , Abhishek Datta  3 , Marom Bikson  4 , Leigh Charvet  2 , Yulin Ge  1
Affiliations

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

Marco Muccio et al. Bioengineering (Basel). .

Abstract

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.

Keywords: fractional amplitude of low-frequency fluctuations (fALFFs); healthy controls; multiple sclerosis (MS); neuromodulation; resting-state functional MRI (rs-fMRI); transcranial direct current stimulation (tDCS).

PubMed Disclaimer

Conflict of interest statement

AD is an employee of and has equity in Soterix Medical Inc., which provided the tDCS equipment used for research use. The City University of New York holds patents on brain stimulation with AD as inventor. MB consults, received grants, assigned inventions, and/or serves on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biovisics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple. The City University of New York holds patents on brain stimulation with MB as inventor. MB also has equity in Soterix Medical Inc. LC has consulted for Ceragem, Neuroelectrics and Syntropic and received speaker fees from Soterix Medical. GP has consulted for Ceragem and received speaker fees from Soterix Medical. LK has received research or programmatic funding, or compensation for consulting, serving on DSMB committees, speaking, travel and meal allowances, or legal/expert testimony from Ebix, Gerson Lehrman, WebMD, Novartis, AAN, NIH, Novartis, Biogen, F. Hoffman/LaRoche, Bristol Myers Squibb, Sedgwick CMS, KBR LLP, Faggiano & Associates Risk Management, MCIC Vermont, EMD Serono, Amgen and Alexion. She has also received royalties for use of the Fatigue Severity Scale by various biopharmaceutical entities.

Figures

Figure 1
Figure 1
(A) Transcranial direct current stimulation (tDCS) setup with an anodal left dorsolateral prefrontal cortex (DLPFC; F3) montage within the 3T MRI scanner. (B) Study design showing resting-state fMRI (rs-fMRI) data acquisition at baseline for healthy controls (HCs) and multiple sclerosis (MS) patients and at follow-up (MS only) after undergoing a treatment of 20 at-home tDCS sessions (MS only).
Figure 2
Figure 2
Preprocessing pipeline used to normalize and standardize the structural and functional datasets of both healthy controls (HCs) and multiple sclerosis (MS) patients before undergoing subject-level and group-level statistical analyses.
Figure 3
Figure 3
Group-level analyses results showing clusters of voxels with significant differences between fALFF measures during-tDCS compared to pre-tDCS in healthy controls (HCs) and multiple sclerosis (MS) patients at baseline and follow-up visits. Notice how, especially in the cortical areas, fALFF seems to be greater during tDCS compared to pre-tDCS (yellow voxels), whilst in more subcortical areas, fALFF measures appear to be decreased from pre- to during-tDCS. The statistical threshold was set to p-voxel < 0.001 and p-cluster < 0.05 and corrected for multiple comparisons using the false discovery rate (FDR). Warmer tones in the color scale indicate an increase in fALFF during tDCS compared to pre-tDCS, whilst colder tones indicate the opposite: a decrease in fALFF.
Figure 4
Figure 4
Group-level analyses addressing the cumulative effects of tDCS by comparing fALFF measures in multiple sclerosis (MS) patients at baseline versus follow-up at pre-tDCS (A) and during-tDCS (B). Notice how, at follow-up, most of the voxel clusters show increased brain activity (fALFF; orange voxels) in pre-tDCS compared to baseline measures, even before re-introducing the stimulation. The statistical threshold was set to p-voxel < 0.001 and p-cluster < 0.05 and corrected for multiple comparisons using the false discovery rate (FDR). Warmer tones in the color scale indicate an increase in fALFF in follow-up compared to baseline, whilst colder tones indicate the opposite: a decrease in fALFF.
Figure 5
Figure 5
Group-level analyses addressing the potential disease-linked differences in baseline resting-state activity by comparing pre-tDCS fALFF measures in multiple sclerosis (MS) patients to healthy controls (HCs). Notice how HCs seem to have greater resting-state activity, especially in subcortical areas (orange voxels), whilst the opposite can be seen in more cortical areas (purple clusters). The statistical threshold was set to p-voxel < 0.001 and p-cluster < 0.05 and corrected for multiple comparisons using the false discovery rate (FDR). Warmer tones in the color scale indicate greater fALFF in MS patients compared to healthy controls, whilst colder tones indicate the opposite: a decrease in fALFF.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Bikson M., Grossman P., Thomas C., Zannou A.L., Jiang J., Adnan T., Mourdoukoutas A.P., Kronberg G., Truong D., Boggio P., et al. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016;9:641–661. doi: 10.1016/j.brs.2016.06.004. - DOI - PMC - PubMed
    1. Dedoncker J., Baeken C., De Raedt R., Vanderhasselt M.A. Combined transcranial direct current stimulation and psychological interventions: State of the art and promising perspectives for clinical psychology. Biol. Psychol. 2021;158:107991. doi: 10.1016/j.biopsycho.2020.107991. - DOI - PubMed
    1. Nitsche M.A., Cohen L.G., Wassermann E.M., Priori A., Lang N., Antal A., Paulus W., Hummel F., Boggio P.S., Fregni F., et al. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008;1:206–223. doi: 10.1016/j.brs.2008.06.004. - DOI - PubMed
    1. Fregni F., El-Hagrassy M.M., Pacheco-Barrios K., Carvalho S., Leite J., Simis M., Brunelin J., Nakamura-Palacios E.M., Marangolo P., Venkatasubramanian G., et al. Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. Int. J. Neuropsychopharmacol. 2021;24:256–313. doi: 10.1093/ijnp/pyaa051. - DOI - PMC - PubMed
    1. Breitling C., Zaehle T., Dannhauer M., Bonath B., Tegelbeckers J., Flechtner H.H., Krauel K. Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS) Front. Cell. Neurosci. 2016;10:72. doi: 10.3389/fncel.2016.00072. - DOI - PMC - PubMed

LinkOut - more resources