Corlier et al. (2025)
- Authors: Juliana Corlier, Hrag Peltekian, Thomas E. Valles, Cole D. Matthews, Doan Ngo, Reza Tadayonnejad, Evan H. Einstein, Scott A. Wilke, Aaron Slan, Margaret G. Distler, Gil Hoftman, Adesewa E. Adelekun, Hanadi A. Oughli, Michael K. Leuchter, Hewa Artin, Ralph J. Koek, Nathaniel D. Ginder, David E. Krantz, Thomas Strouse, Andrew F. Leuchter.
- Institutes: TMS Clinical and Research Service, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA; Division of the Humanities and Social Sciences, California Institute of Technology.
- Publisher: Transcranial Magnetic Stimulation
- Link: DOI
Summary
This study provides preliminary evidence that a non-invasive brain stimulation technique, rTMS, can be safely adapted for ME/CFS patients and may help reduce a wide range of symptoms, including fatigue, pain, and sleep disturbances. The success of the modified protocol underscores the importance of designing flexible clinical trials that can accommodate the limitations imposed by the illness. The finding that baseline brainwave activity might predict who responds best is a promising step toward personalizing treatments and developing objective biomarkers for ME/CFS. While encouraging, these are early findings from a small study that require confirmation in larger, more rigorous controlled trials.
What was researched?
This pilot study evaluated the feasibility, tolerability, and short-term effectiveness of a novel repetitive transcranial magnetic stimulation (rTMS) protocol for treating the primary symptoms of ME/CFS. The protocol involved stimulating two separate brain regions—the left dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1). The researchers also used electroencephalography (EEG) to see if baseline brainwave activity could predict treatment outcomes.
Why was it researched?
ME/CFS is a complex illness with debilitating symptoms and no specific approved treatments. Since rTMS has shown effectiveness in treating similar symptoms (like pain, fatigue, and mood issues) in other conditions, the researchers hypothesized that a dual-target approach could have synergistic effects and benefit multiple ME/CFS symptom domains simultaneously. Previous rTMS studies in ME/CFS were limited, using only a single target or a short course of treatment, so this study aimed to test a more comprehensive protocol.
How was it researched?
This was an open-label pilot study involving 15 female participants diagnosed with ME/CFS. After the first five participants dropped out due to poor tolerability of the initial protocol, the researchers implemented a modified, more flexible protocol for the remaining 10 participants. This modified protocol included 30 sessions of dual-target rTMS with adjustments for stimulation intensity and a less demanding schedule (e.g., multiple sessions in one day to reduce travel). Symptom improvement was measured across five domains (fatigue, pain, mood, sleep, and cognition) from baseline to the end of treatment.
What has been found?
The modified rTMS protocol was found to be safe and well-tolerated, with all 10 participants completing the full 30 sessions. Participants showed, on average, some improvement in all five symptom domains. 70% of the completers were classified as “overall responders,” defined as showing meaningful improvement in at least two of the five symptom areas. The study also found that baseline EEG patterns were associated with outcomes; specifically, lower levels of slow-wave (delta and theta) activity and higher levels of alpha activity were linked to better improvement in fatigue and sleep.
Discussion
The authors emphasize that the study highlights the necessity of adapting clinical trial protocols to the specific needs of the ME/CFS population, as their initial rigid design was not feasible. They acknowledge several limitations, including the open-label design (which can increase placebo effects), the small sample size, and the lack of long-term follow-up to assess the durability of the clinical benefits. The heterogeneity of patient responses suggests that future research should focus on personalizing treatment based on individual symptom profiles.
Conclusion & Future Work
The authors conclude that dual-target rTMS is a potentially safe, tolerable, and promising treatment for the primary symptoms of ME/CFS. The positive results support conducting larger, randomized, and sham-controlled studies to definitively establish the efficacy of this novel treatment approach. Future research should also aim to replicate the EEG findings, which could serve as a biomarker to predict treatment response and guide clinical decisions.