Transcranial direct current stimulation affect neural connectivity and subsequent fibromyalgia symptoms

1. Home-based active transcranial direct current stimulation (HB-a-tDCS) can affect the neural connectivity between the brain regions connecting pain and emotions which can be used as a neural marker for fibromyalgia (FM) management.

2. HB-a-tDCS on the l-DLPFC was positively correlated with sleep quality.

3. HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain. catastrophizing

Evidence Rating Level: 1 (Excellent)

Study Rundown: Fibromyalgia (FM) is a chronic pain condition that is classified as nociplastic pain due to the absence of a straightforward pathophysiological process and intense emotional distress. The neural circuit responsible for pain is highly interconnected and can be represented by functional connectivity (FC). FC and FM symptoms are positively correlated and have been shown to respond to transcranial direct current stimulation (tDCS). The targeted brain regions show different symptomatic management for patients with FM. This randomized clinical study looked to evaluate the effectiveness of self-administered home-based active-tDCS (HB-a-tDCS). 43 women with FM were analyzed after being randomized to receive the treatment (HB-a-tDCS over the left DLPFC or M1) or the sham treatment (HB-a-tDCS over the left DLPFC or M1). Symptomatically, the effect of HB-a-tDCS was positively correlated with sleep quality. HB-a-tDCS on the left DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing. EEG readings also showed specific changes in the lagged coherence connectivity via delta and theta waves. Therefore, HB-a-tDCS can affect the neural connectivity between the brain regions connecting pain and emotions which can be used as a neural marker for FM management. 

Click to read the study in PLoSOne

Relevant Reading: 

Transcranial Direct Current Stimulation (tDCS)

Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials

In-Depth [randomized clinical trial]: Fibromyalgia (FM) is a chronic pain condition that is classified as nociplastic pain due to the absence of a straightforward pathophysiological process and intense emotional distress. This can cause fatigue, musculoskeletal pain, depressive symptoms and other correlates of autonomic dysfunction such as irritable bowel syndrome. The neural circuit responsible for pain is highly interconnected and can be represented by functional connectivity (FC). Patients with FM show changes in the FC of various brain regions including the motor cortex (MC) and left prefrontal cortex (PFC). Increased FC shows a reduction in the efficacy of the descending pain modulatory system (DPMS) which contributes to central sensitization and can explain the pathophysiology of FM. One proposed treatment modality for FM is transcranial direct current stimulation (tDCS) as it modulates neural cortical and subcortical networks. Previous studies have shown tDCS over the primary motor cortex enhanced pain pressure thresholds and improved quality of life for FM patients. When done over the left dorsolateral prefrontal cortex (DLPFC), fatigue levels and pain catastrophizing were reduced suggesting treatment at different regions of the brain changes which symptoms are managed. This randomized clinical trial aimed to evaluate the effectiveness of self-administered home-based active-tDCS (HB-a-tDCS) on the functional connectivity between pain-related areas of the brain, specifically the left DLPFC and M1. 

Participants included women aged 30 to 65 who were diagnosed with FM according to the American College of Rheumatology (ACR) 2016 guidelines and also had a pain score of >6 on the Numerical Pain Scale (NPS 0–10). Of 133 screened participants 43 were included in analysis due to exclusion for logistical concerns, failure to meet FM or pain criteria, and complication with other uncompensated clinical disease. Participants received an HB-tDCS device which was used on the weekdays for 4 weeks, totalling 20 sessions. 2mA of current was applied for 20 minutes over the left M1 (n = 13) or over the DLPFC (n = 16). The sham treatment (HB-s-tDCS and HB-s-M1) were randomized to have half as man participants (n = 8 and n = 6 respectively). The primary outcome looked for lagged coherence connectivity in different EEG frequency bands (delta, theta, alpha-1, alpha-2, beta-1, beta-2, beta-3, and gamma) at resting state. Signals were acquired between related regions in the pain network. EEG recordings were taking post-treatment either with eyes open (EO) or eyes closed (EC).

HB-a-tDCS on the left DLPFC showed a decrease in lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) after treatment (p = 0.048). When comparing this to the sham treatment, there was a decrease in the lagged coherence connectivity in the delta frequency between the two structures (p = 0.017). The EO condition showed left DLPFC HB-a-tDCS increased the lagged coherence connectivity between the left DLPFFC and left ACC in the theta band more than M1 HB-s-tDCS (p = 0.048). Symptomatically, the effect of HB-a-tDCS was positively correlated with sleep quality. HB-a-tDCS on the left DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing. Therefore, modulation of the emotional response to pain was possible with HB-a-tDCS. These were especially seen at lower EEG frequencies and could serve as a neural marker for the alleviation of FM symptoms. The main limitations of this study include the small patient population and the self-administered nature of the treatment. The EEG placement was also chosen to favour ease of use over resolution which could have reduced the rigor of the data collected. Finally, only women were included in this study which is due to most patients with FM being female. Findings should be validated in a larger, more diverse group in the future. Sham tDCSC has also been shown to have high variability which could have led to inconsistent results (see suggested reading for more). 

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