Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex.
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 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 functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels ofN-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (n =19) compared with the analogous hand territory of age- and 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 deafferentation. 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 levels of 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.NEW & NOTEWORTHYThis study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory and motor cortices consequent to upper extremity amputation and its potential reversal through hand replantation or transplantation. We provide evidence for selective alteration of cortical neuronal integrity associated with amputation-related deafferentation that may not be reversible.
Department of Physical Medicine and Rehabilitation, University of Missouri, Columbia, Missouri; cirsteac@health.missouri.edu.|Department of Neurology, Kansas University Medical Center, Kansas City, Kansas.
Carmen M
CM
Cirstea
Department of Neurology, Kansas University Medical Center, Kansas City, Kansas.
In-Young
IY
Choi
Department of Molecular and Integrative Physiology, Kansas University Medical Center, Kansas City, Kansas.
Phil
P
Lee
Department of Psychological Sciences, University of Missouri, Columbia, Missouri.|Brain Imaging Center, University of Missouri, Columbia, Missouri; and.
Huiling
H
Peng
Christine M. Kleinert Institute, Louisville, Kentucky.
Christina L
CL
Kaufman
Department of Psychological Sciences, University of Missouri, Columbia, Missouri.
Scott H
SH
Frey
D000328:Adult; D000368:Aged; D000672:Amputation Stumps / Q000294:innervation / Q000503:physiopathology*; D000674:Amputees; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006225:Hand / Q000294:innervation* / Q000503:physiopathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010591:Phantom Limb / Q000503:physiopathology; D066191:Sensorimotor Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*
D001224:Aspartic Acid; C000179:N-acetylaspartate
N-acetylaspartate; allogeneic hand transplantation and hand replantation; functional MRI-guided 1H-MR spectroscopy; sensorimotor hand territory; unilateral hand amputees