Carmen M Cirstea, In-Young Choi, Phil Lee, Huiling Peng, Christina L Kaufman, Scott H Frey

Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level structural changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used a functional MRI-guided proton magnetic resonance spectroscopy (1H-MRS) to test the hypothesis that unilateral deafferentation is associated with lower absolute levels of N-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (N=19) as compared to the analogous hand territory of age/sex-matched healthy controls (N=28). We also tested whether former amputees (i.e., recipients of replanted (N=3) or transplanted (N=2) hands) exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentiation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus, local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation.