Cortical reorganization in motor cortex after graft of both hands

Paris, June 24, 2001

It is known that the organization of the cerebral cortex is modified after an amputation, but until now no studies had been made of the possible reversibility of this reorganization. A team of neuropsychologists from the CNRS "Institut des sciences cognitives" (ISC, Institute for cognitive science*) in Lyon, together with the Centre hospitalier universitaire de Saint-Etienne (Saint-Etienne University Hospital Center) and the Edouard Herriot Hospital in Lyon used functional magnetic resonance imaging (fMRI) to investigate the dynamics of cortical reorganization in a patientÕs motor cortex before and after bilateral hand transplantation. They demonstrated that the transplanted hands are integrated into the representation of the body scheme and that the transplant reversed the cortical organization that had been induced by the amputation.

How is the brain influenced by changes that occur at the body's periphery? Contrary to the classical view of a predetermined neural wiring pattern, the motor system shows considerable plasticity. In human amputees, the representation of muscles unaffected by the amputation invades the regions of the sensorimotor cortex previously dedicated to the amputated segment. Patients who have undergone transplantation of an upper limb following amputation provide the opportunity to investigate the reversibility of cortical organization after peripheral injury. This was the case of C.D., a patient who underwent a bilateral hand graft performed by Professor J-M Dubernard and his team in Lyon (France) in January 2000.

The members of the neuropsychological research team of the ISC focused on the activations of the motor cortex (M1) and on their evolution over time. The motor cortex, which contains a somatotopic (point-by-point) representation of the body, is the region that sends the motor commands that allow movement. In this study, the movements of the hands and elbows were examined. Before surgery, the movements of the right or left ÒhandÓ (with the forearm muscles active) activated the most lateral part of the hand area in M1, a region spatially close to the face area. Six months after the transplant, this activation expanded medially towards M1, occupying the entire region usually defined as that of the arm. This displacement had already become evident two months after the operation. An analysis of the center of gravity of the activations revealed that after six months, there was a 10 mm displacement for the right hand and a 6 mm displacement for the left hand, going from the lateral to the central part of the hand region.

The activations caused by the elbow movements developed similarly, moving from a central region in M1, which normally corresponds to the area of the hand, toward the upper part of the limb representation, classically defined as the arm region. There too, the centers of gravity of elbow activity moved gradually (six months later, by 8 mm for the right elbow and 7 mm for the left elbow).

There is a strong correlation between the changes observed in the motor cortex for hand and elbow representations in both time and space. The activations of the hand and elbow show a high degree of overlap, which increased before surgery and up to six months afterwards. Similar changes were observed in the somatosensory cortex.

The main findings of this study shows that grafted hands come to be recognized and activated normally by the sensorimotor cortex. This suggests that new peripheral inputs allow a global remodeling of the limb cortical map, leading to the reversal of the functional reorganization caused by the amputation. Furthermore, the spatial trajectories of these activations over time indicate that the cortical rearrangement takes place in an orderly fashion. Thus cortical plasticity follows the normal body representation, i.e. the plan the body used before amputation.

What are the mechanisms underlying this cortical plasticity? The changes within M1 might be the result of a shift in the strength of the activations among the existing connections. The activation of the hand area triggered by elbow movements during the phase prior to the transplant could be explained as resulting from a change in the weight of these connections. In other words, the representation of the elbow appears to have invaded the region of the amputated hand because of the absence of peripheral inputs that target this region. The hand graft seems to have restored the efficacy of the original connections at the expense of the elbow representation, thus allowing typical features of cortical organization to reappear in the cortical map.

Reference: Cortical reorganization in motor cortex after graft of both hands, Pascal Giraux, Angela Sirigu, Fabien Schneiderandt, Jean-Michel Dubernard. Nature Neuroscience, July 2001.

- Pascal Giraux: Institute for Cognitive Science, CNRS, Bron, and Department of Physical Medicine (Doctor and Rehabilitation Specialist), CHU, Saint-Etienne
- Angela Sirigu: Neuropsychology team (Scientific Director), Institute for Cognitive Science, CNRS, Bron
- Fabien Schneider (research engineer): Radiology Department, CHU, Saint-Etienne
- Jean-Michel Dubernard: Head of the Department of Surgical Transplantation, Edouard Herriot Hospital, Lyon

Figure A
Movements of the right hand	Movements of the left hand
Figure B
Before transplantation	Six months after transplantation
Caption of figures A and B: Activation maps obtained in the motor cortex when the patient makes hand movements. Figure A : The representation of the body in the brain is reversed. The image on the left shows the activations in the left primary motor cortex (M1), which controls the movements of the right hand, and vice versa in the image on the right. The activations obtained during the examination prior to transplantation are shown in red, and those six months after are shown in blue. The areas of overlap between the two examinations are shown in green. Figure B : Horizontal view of the cerebral cortex of the transplanted patient. The image on the left shows that, before transplantation, a contraction of the muscles that control the right hand activates the facial region but not the hand region. On the right, the same muscular contraction six months after transplantation activates the hand region.

Researcher contact:
Angela Sirigu
Tel: + 33 4 37 91 12 31/ + 33 4 37 91 12 12
Fax: +33 4 37 91 12 10
E-mai l: sirigu@isc.cnrs.fr

Department of Life Sciences contact:
Thierry Pilorge
Tel: +33 1 44 96 40 26
E-mail : thierry.pilorge@cnrs-dir.fr

Press contact :
Martine Hasler
Tel : +33 1 44 96 46 35
E-mail : martine.hasler@cnrs-dir.fr