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Carpal Tunnel Syndrome (CTS) is an entrapment neuropathy of the median nerve that alters the organization of the brain's primary somatosensory cortex (S1), both structurally and functionally. Our prior research also demonstrated that electro-acupuncture (EA), both local and remote/distal to the wrist, but not sham acupuncture, improved S1 somatotopy and peripheral (median) nerve conduction. However, the mechanisms linking EA-evoked brain response during therapy with improved clinical outcomes are unknown. We investigated functional connectivity during both rest and sustained electro-acupuncture at baseline in healthy controls and CTS patients and after 8 weeks of acupuncture therapy (local, distal, or sham EA) in CTS patients. Six minutes of 3T BOLD fMRI data were collected at rest and during EA. Data were processed with FMRIPREP and FSL to generate maps of connectivity between the S1 hand region and the rest of the brain (z > 2.3, pFWE < 0.05). Compared to healthy controls, CTS patients showed decreased resting state functional connectivity between S1 and the thalamic pulvinar nucleus. Increases in S1/pulvinar functional connectivity strength following verum therapy (combined local and distal group) were correlated with improvements in median nerve velocity (r=0.38, p=0.035). During tonic local EA, compared to healthy controls, CTS patients demonstrated increased functional connectivity between S1 and left anterior hippocampus. Following local EA therapy, S1/hippocampus connectivity significantly decreased and this decrease was associated with improvements in patients’ function (r=0.64, p=0.01) and median nerve velocity (r=-0.62, p=0.013). Stimulus-evoked connectivity adds mechanistic insight to more common resting fMRI connectivity approaches. Decreased resting S1/pulvinar connectivity might reflect changes in sensory information control and sensation awareness, while S1/hippocampus connectivity during delivery of local EA can track improvements in patient function and median nerve health. Functional connectivity between S1 and sub-cortical limbic and association regions may specifically support improved CTS response to local EA therapy. NIH, NCCIH (R61-AT009306, P01-AT002048, R01-AT004714); KIOM (K15050).
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