S1 Brain Connectivity in Carpal Tunnel Syndrome Underlies Median Nerve and Functional Improvement Following Electro-Acupuncture

Harrison Fisher; Roberta Sclocco; Yumi Maeda; Jieun Kim; Cristina Malatesta; Jessica Gerber; Joseph Audette; Norman Kettner; Vitaly Napadow

doi:10.3389/fneur.2021.754670

S1 Brain Connectivity in Carpal Tunnel Syndrome Underlies Median Nerve and Functional Improvement Following Electro-Acupuncture

Front Neurol. 2021 Oct 27:12:754670. doi: 10.3389/fneur.2021.754670. eCollection 2021.

Authors

Harrison Fisher¹, Roberta Sclocco^{1

2

3}, Yumi Maeda^{1

2}, Jieun Kim⁴, Cristina Malatesta³, Jessica Gerber¹, Joseph Audette⁵, Norman Kettner², Vitaly Napadow^{1

2

3}

Affiliations

¹ Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
² Department of Radiology, Logan University, Chesterfield, MO, United States.
³ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, United States.
⁴ Division of Clinical Medicine, Korea Institute of Oriental Medicine, Daejeon, South Korea.
⁵ Department of Pain Medicine, Harvard Vanguard Medical Associates, Atrium Health, Boston, MA, United States.

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.

Keywords: carpal tunnel syndrome; electro-acupuncture; functional connectivity; functional magnetic resonance imaging; peripheral nerve function.