Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the 
median nerve at the wrist. Acupuncture is a minimally-invasive and conservative 
therapeutic option, and while rooted in a complex practice ritual, acupuncture 
overlaps significantly with many conventional peripherally-focused 
neuromodulatory therapies. However, the neurophysiological mechanisms by which 
acupuncture impacts accepted subjective/psychological and 
objective/physiological outcomes are not well understood. Eligible patients (n = 
80, 65 female, age: 49.3 ± 8.6 years) were enrolled and randomized into three 
intervention arms: (i) verum electro-acupuncture 'local' to the more affected 
hand; (ii) verum electro-acupuncture at 'distal' body sites, near the ankle 
contralesional to the more affected hand; and (iii) local sham 
electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy 
was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome 
Questionnaire assessed pain and paraesthesia symptoms at baseline, following 
therapy and at 3-month follow-up. Nerve conduction studies assessing median 
nerve sensory latency and brain imaging data were acquired at baseline and 
following therapy. Functional magnetic resonance imaging assessed somatotopy in 
the primary somatosensory cortex using vibrotactile stimulation over three 
digits (2, 3 and 5). While all three acupuncture interventions reduced symptom 
severity, verum (local and distal) acupuncture was superior to sham in producing 
improvements in neurophysiological outcomes, both local to the wrist (i.e. 
median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 
cortical separation distance). Moreover, greater improvement in second/third 
interdigit cortical separation distance following verum acupuncture predicted 
sustained improvements in symptom severity at 3-month follow-up. We further 
explored potential differential mechanisms of local versus distal acupuncture 
using diffusion tensor imaging of white matter microstructure adjacent to the 
primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 
49.7 ± 9.9 years old), patients with carpal tunnel syndrome demonstrated 
increased fractional anisotropy in several regions and, for these regions we 
found that improvement in median nerve latency was associated with reduction of 
fractional anisotropy near (i) contralesional hand area following verum, but not 
sham, acupuncture; (ii) ipsilesional hand area following local, but not distal 
or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not 
local or sham, acupuncture. As these primary somatosensory cortex subregions are 
distinctly targeted by local versus distal acupuncture electrostimulation, 
acupuncture at local versus distal sites may improve median nerve function at 
the wrist by somatotopically distinct neuroplasticity in the primary 
somatosensory cortex following therapy. Our study further suggests that 
improvements in primary somatosensory cortex somatotopy can predict long-term 
clinical outcomes for carpal tunnel syndrome.