The ability to induce neuroplasticity with non-invasive brain stimulation techniques offers a unique opportunity to examine the human brain systems involved in pain modulation. In experimental and clinical settings, the primary motor cortex (M1) is commonly targeted to alleviate pain, but its mechanism of action remains unclear. Using dynamic causal modelling (DCM) and Bayesian model selection (BMS), we tested seven competing hypotheses about how TMS modulates the directed influences (or effective connectivity) between M1 and three distinct cortical areas of the medial and lateral pain systems, including the insular (INS), anterior cingulate cortex (ACC), and parietal operculum (PO). The dataset included a novel fMRI acquisition collected synchronously with M1 stimulation during rest and while performing a simple hand motor task. DCM and BMS showed a clear preference for the fully connected model in which all cortical areas receive input directly from M1, with facilitation of the connections INS®M1, PO®M1, and ACC®M1, plus increased inhibition of their reciprocal connections. An additional DCM analysis comparing the reduced models only corresponding to networks with a sparser connectivity within the full model, showed that M1 input into the INS is the second-best model of plasticity following TMS manipulations. The results reported here provide a starting point forinvestigating whether pathway-specific targeting involving M1«INS improves analgesic response beyond conventional targeting. We eagerly await future empirical data and models that tests this hypothesis.
Hodkinson, D. J., Bungert, A., Bowtell, R. W., Jackson, S. R., & Jung, J. (2021). Operculo-Insular and Anterior Cingulate Plasticity Induced by Transcranial Magnetic Stimulation in the Human Motor Cortex: A Dynamic Casual Modelling Study. Journal of Neurophysiology, 125(4), 1180-1190. https://doi.org/10.1152/jn.00670.2020