Summary: Researchers identified specific neurochemical changes in brain regions that reorganize after hand amputation, and found that some of these changes may remain even after surgical reattachment or transplantation of the hand.
How Hand Amputation and Reattachment Affect the Brain
Source: University of Missouri Columbia.
When a hand is lost through amputation, the nerves that transmit sensation and control movement are severed. This deafferentation triggers substantial functional and structural reorganization in the brain regions that previously served the missing limb. A team at the University of Missouri used noninvasive magnetic resonance spectroscopy (MRS) to detect neurochemical changes in those brain areas, finding evidence of reduced neuronal integrity. Importantly, they observed that some of these neurochemical alterations persisted in patients who regained a hand through replantation or transplantation, even when sensory and motor function improved.
“When there is a sudden increase or decrease in stimulation that the brain receives, the function and structure of the brain begin to change,” said Carmen M. Cirstea, M.D., Ph.D., research assistant professor of Physical Medicine and Rehabilitation and lead author of the study. “Using MRS to examine areas of the brain that once controlled hand function, we observed specific changes at the neurochemical level after amputation and after surgical reattachment or transplantation.”
Cirstea and co-author Scott Frey, Ph.D., Miller Family Chair in Cognitive Neuroscience, evaluated three groups: current hand amputees, former amputees who had their hands replanted or transplanted, and healthy control subjects. While participants performed simple finger-flexing tasks to activate sensorimotor regions on both sides of the brain, the team measured levels of N-acetylaspartate (NAA), a metabolite commonly used as a marker of neuronal health and integrity.
The study found that NAA concentrations in the cortical hand territories of current amputees were significantly lower than those in matched healthy controls. Unexpectedly, NAA values in the small group of replantation and transplantation patients were similar to those of current amputees rather than matching control levels. These results suggest that chronic deafferentation is associated with persistently altered neuronal integrity, and that surgical restoration of the hand does not always reverse these neurochemical changes.
“Previous work has documented large-scale cortical reorganization after limb injuries that reduce sensory and motor input,” Frey explained. “Our findings add a neurochemical perspective: nerve injuries appear to affect neuronal integrity in the mature brain, and these effects may persist even when some sensory and motor abilities return following surgical repair.”
The study used a functional MRI-guided proton magnetic resonance spectroscopy approach to localize and measure metabolites in the primary sensorimotor hand territories contralateral to the missing or restored hand. The principal finding was lower NAA in current amputees compared with age- and sex-matched healthy controls. NAA levels in replanted and transplanted patients fell within the same reduced range as current amputees rather than resembling control values, suggesting limited or incomplete neurochemical recovery after reafferentation in these individuals.
Researchers emphasize caution in interpreting the findings for replantation and transplantation cases because only five such patients were included in the study (three replanted, two transplanted). The small sample size limits definitive conclusions about reversibility of neurochemical changes and highlights the need for additional research with larger patient groups and longitudinal follow-up.
The study, titled “Magnetic Resonance Spectroscopy of Current Hand Amputees Reveals Evidence for Neuronal-level Changes in Former Sensorimotor Cortex,” was published in the Journal of Neurophysiology and was recognized by the American Physiological Society as one of the top original research papers published in April 2017.
Funding: This work was supported by grants from the United States Army Medical Research Acquisition Activity, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, and the U.S. Department of Defense. The authors reported no conflicts of interest related to the study.
Source: University of Missouri Columbia
Image source: Image adapted from the University of Missouri news release.
Original research: Carmen M. Cirstea, In-Young Choi, Phil Lee, Huiling Peng, Christina L. Kaufman, and Scott H. Frey. “Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex,” Journal of Neurophysiology. Published online April 1, 2017. doi:10.1152/jn.00329.2016
Abstract
Deafferentation following upper-limb amputation is accompanied by large-scale functional reorganization of primary sensory and motor cortical maps contralateral to the injury. Animal models indicate a range of cellular-level consequences, including depressed neuronal metabolism and potential neuronal loss. To investigate whether similar neuronal-level changes occur in chronic human amputees, the study used fMRI-guided proton magnetic resonance spectroscopy to compare N-acetylaspartate (NAA) levels in the sensorimotor hand territory contralateral to the missing hand with those in matched healthy controls. Current amputees (n = 19) showed lower NAA levels than controls (n = 28), and NAA decreased with increasing time since amputation. Contrary to expectations, former amputees who had hands replanted (n = 3) or transplanted (n = 2) exhibited NAA levels within the range seen in current amputees rather than resembling controls. These findings suggest altered neuronal integrity in the deafferented cortex of chronic amputees and indicate that neurochemical changes may not be readily reversible following surgical reafferentation.
This summary presents findings from the published peer-reviewed study cited above. Further research is needed to clarify the time course and potential reversibility of neurochemical changes after limb loss and surgical restoration of peripheral connections.