Abstract
Carpal Tunnel Syndrome (CTS) is a median nerve entrapment neuropathy that alters primary somatosensory cortex (S1) organization. While electro-acupuncture (EA), a form of peripheral neuromodulation, has been shown to improve clinical and neurophysiological CTS outcomes, the role of EA-evoked brain response during therapy (within and beyond S1) for improved outcomes is unknown. We investigated S1-associated whole brain fMRI connectivity during both a resting and sustained EA stimulation state in age-matched healthy controls (N = 28) and CTS patients (N = 64), at baseline and after 8 weeks of acupuncture therapy (local, distal, or sham EA). Compared to healthy controls, CTS patients at baseline showed decreased resting state functional connectivity between S1 and thalamic pulvinar nucleus. Increases in S1/pulvinar connectivity strength following verum EA therapy (combined local and distal) were correlated with improvements in median nerve velocity (r = 0.38, p = 0.035). During sustained local EA, compared to healthy controls, CTS patients demonstrated increased functional connectivity between S1 and anterior hippocampus (aHipp). Following 8 weeks of local EA therapy, S1/aHipp connectivity significantly decreased and greater decrease was associated with improvement in patients' functional status (r = 0.64, p = 0.01) and increased median nerve velocity (r = −0.62, p = 0.013). Thus, connectivity between S1 and other brain areas is also disrupted in CTS patients and may be improved following EA therapy. Furthermore, stimulus-evoked fMRI connectivity adds therapy-specific, mechanistic insight to more common resting state connectivity approaches. Specifically, local EA modulates S1 connectivity to sensory and affective processing regions, linked to patient function and median nerve health.
Highlights
Carpal tunnel syndrome (CTS) is an entrapment neuropathy of the median nerve characterized by sensations of pain and paresthesia and reduced velocity for impulses traveling over the affected median nerve
Intrinsic, connectivity and state-specific connectivity during EA treatment, revealing dynamic treatment responses that evolve as therapy progresses
We focused our connectivity analyses on the S1 subregion encoding the cortical representation of median-nerve innervated digit 2 (D2), previously shown to exhibit shifted somatotopy in Carpal Tunnel Syndrome (CTS) patients [5]
Summary
Carpal tunnel syndrome (CTS) is an entrapment neuropathy of the median nerve characterized by sensations of pain and paresthesia and reduced velocity (or increased latency) for impulses traveling over the affected median nerve. A longitudinal course of EA therapy applied either locally (i.e., hand/wrist area) or distally (i.e., leg/ankle area) reduced CTS symptoms and improved both peripheral nerve function and central maladaptive neuroplasticity within S1 [3], suggesting the involvement of brain-based mechanisms of action. We hypothesized that [1] CTS-associated functional plasticity extends beyond S1 somatotopy to include resting S1 connectivity between cortical representations for affected digits and other brain regions, [2] S1 connectivity during EA differs between CTS and healthy controls, and [3] longitudinal distal and local EA therapy alter functional connectivity patterns linked to CTS pathology and clinical outcomes
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