Global connectivity-based target selection for rTMS did not enhance analgesic efficacy in chronic pain patients compared to classic M1 stimulation
In a randomized, double-blind trial, 90 chronic pain patients received 12 sessions of rTMS over 8 weeks, comparing stimulation of the cortical site with lowest pre-therapy global connectivity, highest connectivity, or classic M1 stimulation. No significant between-group differences were found for the primary outcome (≥30% pain reduction) or secondary outcomes (all p > 0.05). Exploratory analyses showed that lower local M1 connectivity was associated with greater pain reduction only in the Classic-M1 group (r = 0.50, p = 0.005).
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Global connectivity-based target selection for rTMS did not enhance analgesic efficacy in chronic pain patients compared to classic M1 stimulation The current body of evidence comprises 1 study, including 1 randomized controlled trial. EvidenceHub rates the overall confidence at 48/100 (low).
The Claim
Global connectivity-based target selection for rTMS did not enhance analgesic efficacy in chronic pain patients compared to classic M1 stimulation
This conclusion is most relevant to: 90 patients with chronic pain.
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Personalizing neuromodulation for chronic pain: A connectivity-guided trial. (Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026) —
How It Works
The proposed biological pathway:
- ▸Pre-therapy TMS-evoked EEG potentials recorded from four cortical targets
- ▸Connectivity quantified using distance-weighted, phase-based measure (debiased wPLI)
- ▸Stimulation applied to site with lowest global connectivity (Low-Connectivity group), highest connectivity (High-Connectivity group), or classic M1 (Classic-M1 group)
- ▸No significant difference in pain reduction between groups; local M1 connectivity correlated with outcome only in Classic-M1 group
Who Might Benefit
Evidence fit by population:
- ▸90 patients with chronic pain
Recommended Dose
12 rTMS sessions over 8 weeks
Limitations & Caveats
Important context when interpreting this evidence:
- ▸Exploratory mechanistic analyses were prespecified but not primary, limiting causal inference
- ▸Findings from local M1 connectivity association are hypothesis-generating and require prospective validation
Frequently Asked Questions
Did the novel connectivity-guided rTMS approach improve pain relief compared to standard M1 stimulation?▼
No, the study found no significant differences between the connectivity-guided groups and the classic M1 stimulation group for any primary or secondary outcomes.
What was the primary outcome measure in this trial?▼
The primary outcome was the proportion of patients achieving at least 30% reduction in pain intensity after 8 weeks of rTMS.
How was cortical connectivity measured in this study?▼
Connectivity was quantified using a distance-weighted, phase-based measure called the debiased weighted phase lag index (wPLI), derived from TMS-evoked EEG potentials recorded from four cortical targets.
What did the exploratory analysis reveal about local M1 connectivity?▼
Lower pre-therapy local M1 connectivity was associated with greater pain reduction in the Classic-M1 group (r = 0.50, p = 0.005), but not in the Low- or High-Connectivity groups.
References
- 1.De Martino E, Midtgaard Bach M, Nascimento Couto B, Jakobsen A, Nascimento Martins P, Ingemann-Molden S, Casali AG, Graven-Nielsen T, Ciampi de Andrade D. “Personalizing neuromodulation for chronic pain: A connectivity-guided trial..” Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. PMID: 42456233 DOI: 10.1016/j.neurot.2026.e00960