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Personalizing neuromodulation for chronic pain: A connectivity-guided trial.
Enrico De Martino1, Margit Midtgaard Bach1, Bruno Nascimento Couto1
1Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Faculty of Medicine, Aalborg University, Aalborg, Denmark.
Repetitive transcranial magnetic stimulation (rTMS) for chronic pain did not show improved pain relief when targeting brain regions based on connectivity. The study found no significant differences between connectivity-based targeting and standard motor cortex stimulation for pain reduction.
Area of Science:
- Neuroscience
- Pain Management
- Neuromodulation
Background:
- Chronic pain affects millions globally, with limited effective treatments.
- Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique explored for pain relief.
- Current rTMS protocols often target the primary motor cortex (M1), but optimizing target selection remains a challenge.
Purpose of the Study:
- To evaluate the efficacy of rTMS for chronic pain using a novel target-selection strategy based on pre-therapy cortical connectivity.
- To compare the analgesic effects of stimulating cortical sites with low versus high pre-therapy global connectivity.
- To compare these novel strategies against the classic M1 stimulation approach.
Main Methods:
- A randomized, double-blind, controlled trial involving 90 patients with chronic pain.
- rTMS treatment administered over 8 weeks, with patients randomized to Low-Connectivity, High-Connectivity, or Classic-M1 groups.
- Cortical connectivity quantified using the debiased weighted phase lag index (wPLI) from TMS-evoked EEG potentials.
Main Results:
- No significant differences in the primary outcome (≥30% pain reduction) or secondary outcomes were observed between the three groups.
- Exploratory analyses suggested a potential association between lower local M1 connectivity and greater pain reduction in the Classic-M1 group, requiring further validation.
- Global connectivity-based target selection did not enhance the analgesic efficacy of rTMS for chronic pain.
Conclusions:
- The study did not support the hypothesis that targeting brain regions based on pre-therapy global connectivity improves rTMS efficacy for chronic pain.
- Findings suggest that optimizing rTMS for chronic pain may require different strategies than those explored here.
- Further research is needed to validate the exploratory findings regarding local M1 connectivity and its association with pain relief.
