Modulation of neural networks and symptom correlated in fibromyalgia: A randomized double-blind multi-group explanatory clinical trial of home-based transcranial direct current stimulation

Rael Lopes Alves; Maxciel Zortea; Paul Vicuña Serrano; Vani Dos Santos Laranjeira; Betina Franceschini Tocchetto; Leticia Ramalho; Camila Fernanda da Silveira Alves; Rafaela Brugnera Tomedi; Rodrigo Pereira de Almeida; Samara Machado Bruck; Liciane Medeiros; Paulo R S Sanches; Danton P Silva Jr; Iraci L S Torres; Felipe Fregni; Wolnei Caumo

doi:10.1371/journal.pone.0288830

Modulation of neural networks and symptom correlated in fibromyalgia: A randomized double-blind multi-group explanatory clinical trial of home-based transcranial direct current stimulation

PLoS One. 2024 Nov 13;19(11):e0288830. doi: 10.1371/journal.pone.0288830. eCollection 2024.

Authors

Rael Lopes Alves^{1

2}, Maxciel Zortea^{2

3}, Paul Vicuña Serrano^{1

2}, Vani Dos Santos Laranjeira^{1

2}, Betina Franceschini Tocchetto^{1

2}, Leticia Ramalho^{1

2}, Camila Fernanda da Silveira Alves^{1

2}, Rafaela Brugnera Tomedi², Rodrigo Pereira de Almeida², Samara Machado Bruck², Liciane Medeiros^{2

4}, Paulo R S Sanches⁵, Danton P Silva Jr⁵, Iraci L S Torres^{1

6}, Felipe Fregni⁷, Wolnei Caumo^{1

2

8

9}

Affiliations

¹ Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
² Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
³ Health School, University of Vale do Rio dos Sinos, São Leopoldo, Porto Alegre, Brazil.
⁴ Post-Graduate Program in Health and Human Development, Universidade La Salle, Canoas, Brazil.
⁵ Laboratory of Biomedical Engineer, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁶ Pharmacology of Pain and Neuromodulation: Pre-Clinical Investigations Research Group, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.
⁷ Laboratory of Neuromodulation and Center for Clinical Research Learning, Physics and Rehabilitation Department, Spaulding Rehabilitation Hospital, Boston, Massachusetts, United States of America.
⁸ Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁹ Department of Surgery, School of Medicine, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Abstract

Background: Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity in patients with fibromyalgia (FM). This multi-group randomized clinical trial compared home-based active tDCS (HB-a-tDCS) on the left dorsolateral prefrontal cortex (l-DLPFC) or home-based sham tDCS (HB-s-tDCS), and HB-a-tDCS or HB-s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies.

Methods: We included 48 women with FM, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of HB-a-tDCS 2mA or HB-s-tDCS, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC).

Results: In the EC condition, comparing pre to post-treatment, the HB-a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t = -3.542, p = .048). The l-DLPFC HB-a-tDCS compared to HB-s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t = -4.000, p = .017). In the EO condition, the l-DLPFC HB-a-tDCS compared to M1 HB-s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t = -4.059, p = .048). Regression analysis demonstrated that the HB-a-tDCS effect on the l-DLPFC was positively correlated with sleep quality. On the other hand, the HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing.

Conclusions: These results show that HB-a-tDCS affects the neural connectivity between parts of the brain that control pain's emotional and attentional aspects, which are most noticeable at lower EEG frequencies in a rest state. This effect on neural oscillations could serve as a neural marker associated with its efficacy in alleviating fibromyalgia symptoms.

Clinical trial registration: identifier [NCT03843203].

Copyright: © 2024 Lopes Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Aged
Dorsolateral Prefrontal Cortex / physiopathology
Double-Blind Method
Electroencephalography*
Female
Fibromyalgia* / physiopathology
Fibromyalgia* / therapy
Humans
Middle Aged
Motor Cortex / physiopathology
Nerve Net / physiopathology
Prefrontal Cortex / diagnostic imaging
Prefrontal Cortex / physiopathology
Transcranial Direct Current Stimulation* / methods

Associated data

ClinicalTrials.gov/NCT03843203

Grants and funding

The following provided support for this study: (i) Committee for the Development of Higher Education Personnel (CAPES) through the academic excellence program (PROEX) (grants doctorate scholarships to RLA, and PVS), and the post-graduation national program (PNPD) (grant to MZ, LR, and CFSA). (ii) National Council for Scientific and Technological Development (CNPq) (Grants no 420826/2018-1 and 19/2551-0000716-7 to WC). (iii) Postgraduate Research Group at the Hospital de Clínicas de Porto Alegre (FIPE-HCPA) to WC (project no. 2020-0369). (iv) Brazilian Innovation Agency (FINEP) to WC, and ILST (process no. 1245/13). (v) Foundation for the Support of Research at Rio Grande do Sul (FAPERGS) Ministry of Science and Technology. National Council for Scientific and Technological Development - (CNPq)/ Health Secretary of State of Rio Grande do Sul, Brazil (SEARS) n. 03/2017 (PPSUS) to WC (Grant no: 17/2551-0001). Study design, data collection, analysis, manuscript preparation, or publication decisions had no interference from funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.