Abstract

Paresthesia-and pain-dominant subgroups have been noted in carpal tunnel syndrome (CTS), a peripheral neuropathic disorder characterized by altered primary somatosensory/motor (S1/M1) physiology. We aimed to investigate whether brain morphometry dissociates these subgroups. CTS subjects were evaluated with nerve conduction studies, while symptom severity ratings were used to allocate subjects into paresthesia-dominant (CTS-paresthesia), pain-dominant (CTS-pain), and pain/paresthesia non-dominant (not included in further analysis) subgroups. Structural brain MRI data were acquired at 3T using a multi-echo MPRAGE T1-weighted pulse sequence, and gray matter cortical thickness was calculated across the entire brain using validated, automated methods. CTS-paresthesia subjects demonstrated reduced median sensory nerve conduction velocity (p=0.05) compared to CTS-pain. In addition, cortical thickness in pre- and post-central gyrus (S1/M1 hand area) contralateral to the more affected hand was significantly reduced in CTS-paresthesia compared to CTS-pain. Moreover, in CTS-paresthesia subjects, pre-central cortical thickness was negatively correlated with paresthesia severity (r(34)=-0.40, p=0.016) and positively correlated with median nerve sensory velocity (r(36)=0.51, p=0.001), but not with pain severity. Conversely, in CTS-pain subjects, contralesional S1 (r(9)=0.62, p=0.042) and M1 (r(9)=0.61, p=0.046) cortical thickness was correlated with pain severity, but not median nerve velocity or paresthesia severity. This double dissociation in somatotopically-specific S1/M1 areas suggests a neuroanatomical substrate for symptom-based CTS subgroups. Such fine-grained subgrouping of CTS may lead to improved personalized therapeutic approaches, based on superior characterization of the linkage between peripheral and central neuroplasticity.