CEREBRAL PLASTICITY IN CROSSED C7 GRAFTS OF THE BRACHIAL PLEXUS: AN fMRI STUDY

JEAN-YVES BEAULIEU, M.D.,1* JERRY BLUSTAJN, M.D.,1 FREDERIC TEBOUL, M.D.,1 PATRICE BAUD, M.D.,3 SCANIA DE SCHONEN, M.D.,4 JEAN-BAPTISTE THIEBAUD, M.D.,3 and CHRISTOPHE OBERLIN, M.D.1

In order to rescue elbow exion after complete accidental avulsion of one brachial plexus, seven patients underwent a neurotization of the biceps with bers from the contralateral C7 root. The C7 bers used for the graft belonged to the pyramidal pathway, which descends from the cerebral hemisphere ipsilateral to the damaged plexus, and which controls extension and abduction of the contralateral arm. After several months of reeducation, a functional magentic resonance imaging study was performed with a 1.5 tesla clinical magnetic resonance scan system, in order to investigate the central neural networks involved in the recovery of elbow exion. Functional brain images were acquired under four conditions: exion of each of the two elbows, and imagined exion of each elbow. Results show that exion of the neurotized arm is associated with a bilateral network activity. The contralateral cortex originally involved in control of the rescued arm still participates in the elaboration and control of the task through the bilateral premotor and primary motor cortex. The location of the ipsilateral clusters in the primary motor, premotor, supplementary motor area, and posterior parietal areas is similar among patients. The location of C contralateral activations within the same areas differs across patients. V 2006 Wiley-Liss, Inc. Microsurgery 26:303310, 2006.

Studies of cortical reorganization in adults with peripheral neuropathologies show an increasing recruitment of networks within cortical motor areas when patients perform tasks which normally involve the pathological pathway.1,2 Similarly, young adults who undergo a neurotization connecting the bers of the intercostal nerve with the biceps show a recovery of elbow exion. Within 23 years after surgery, in most cases, exion and ventilatory commands become segregated. Functional investigations (with transcranial magnetic stimulation and motor evoked potential, and functional magnetic resonance imaging) showed relocalization of the motor command within the motor cortex, and progressive reorganization of cortical networks activated.36 Another method for rescuing arm exion consists of neurotization of the biceps with contralateral root C7.710 This technique results in no long-term critical decits of the donor limb.11,12 However, it is not known how conscious motor cortical control is reorganized in these cases. Here, we report on 7 adults who had severe damage of the brachial plexus on one side, and who underwent neurotization of the biceps with a crossed C7 graft. These bers are normally involved in adduction and extension of the intact arm. By neurotization and the crossed C7 graft, exion of the deafferented arm is no longer under the control of the contralateral hemisphere, but rather under the control of the ipsilateral hemisphere. Ultimately, the cerebral hemi1 2

sphere ipsilateral to the injured plexus will control extension of the intact arm and exion of the neurotized arm. In order to identify the cortical neural networks involved in recovery of the arm exion command, functional magnetic resonance imaging (fMRI) was performed under four conditions. Cortical activation area, correlated with real exion and with imagined exion of the injured and the preserved arm, were compared. A greater knowledge concerning the locus of neural reorganization and the relationships between the locus and the degree of recovery can contribute to improve reeducation procedures, as well as to further the progress of neurotization. This study was approved by the Committee for Ethics of Ambroise Pare Hospital (Paris, France).
METHODS Patients

Department of Orthopedics and Trauma, CHU-Bichat, Paris, France Department of Radiology, Foundation Rothschild, Paris, France 3 Department of Neurosurgery, Foundation Rothschild, Paris, France 4 UMR8605, CNRS-Paris 5, and E9935 INSERM, Hopital Robert Debre, Paris, France Grant sponsor: Department of Neurosurgery, Foundation Rothschild. *Correspondence to: J.Y. Beaulieu, Service de Chirurgie Orthopedique et Traumatologique, CHU-Bichat, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. E-mail: Jean-Yves.BEAULIEU@wanadoo.fr Received 25 November 2005; Accepted 15 January 2006 Published online 2 May 2006 in Wiley InterScience (www.interscience.wiley. com). DOI 10.1002/micr.20243
C V

Seven male patients (Table 1) with severe trauma of the brachial plexus due to a trafc accident, and who were treated with a cross-C7 neurotization of the paralyzed biceps, were selected for this study. Ages ranged from 2047 years (mean age, 29 years), and all patients were right-handed, except for one (P6). Additional patients were excluded from the sample either because they did not show any clinically detected contraction of the neurotized muscle or because they could not perform an MRI (due to claustrophobia, a pacemaker, or an intraocular metallic object). All patients had complete avulsion of the ve roots of the superior member. Each patient underwent a clinical evaluation for residual motor functions and signs of associated neurological lesions. A cervical myeloscan was performed for each patient. Avulsion of the plexus roots was observed in all patients. All surgical interventions were performed by the same medical team at Bichat Hospital between 19982001.

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Table 1. Population of Patients Age (years) 36 20 33 25 25 24 47 Time course for surgery (months) right right right right right left left 2 6 5 2 5 1 4 Cross Cross Cross Cross Cross Cross Cross C7 C7 C7 C7 C7 C7 C7 to to to to to to to Muscle grade nerve nerve nerve M4 M2 M1 M2 M2 M2 M4 Time course for fMRI (months) 18/36 27 18/36 18 21 13 25

Patients 1 2 3 6 7 4 5

Handedness Right-handed Right-handed Right-handed Left-handed Right-handed Right-handed Right-handed Total Total Total Total Total Total Total

Lesions avulsion, avulsion, avulsion, avulsion, avulsion, avulsion, avulsion,

Surgery musculocutaneous musculocutaneous musculocutaneous lateral cord lateral cord musculocutaneous musculocutaneous

nerve nerve

Neurotization was performed with part of the C7 root contralateral to the musculocutaneous nerve or lateral cord of the damaged brachial plexus. Electrical stimulation during surgery was used to select neural bers innervating proximal muscles within the C7 root (i.e., bers involved in extension and adduction of the contralateral healthy arm). In all cases, grafts taken from the sural nerves were used to perform grafting of the C7 root onto the musculocutaneous nerve or the lateral cord, in order to restore elbow exion. Surgery was performed within 16 months after injury (average delay, 3 months and 8 days). After surgery, screening was regularly performed in each patient: the Tinel sign was regularly assessed; reinnervated muscle strength was evaluated on a 5-degree scale; and motor command was clinically evaluated. The contralateral intact arm was screened for sensitivity and muscular strength, to detect any decit in the C7 root territory (Tables 1 and 2). The rst fMRI brain imaging was performed after the rst clinical sign of contractions in the reinnervated muscle. The delay between surgery and fMRI ranged from 13 25 months (average delay, 17 months and 5 days). A second functional brain imaging was performed in 2 patients 18 months after the rst, which was 36 months after surgery.
Tasks

extension of the arm, placing the arm back in the same extended position after each exion. The rate of exion was about one exion every 2 s. 3. Imaginary arm exion: intact arm. The rate of imaginary exion was similar to that of the injured arm. 4. Flexion of the preserved arm: exion was performed in the same way as for the injured arm. Extension was passively performed by the experimenter. The rate of exion was similar to that in condition 2. During each task, rest and action periods were alternated. The duration of each rest period (R) was 30 s, followed by a 30 s active period (A), for a total of four resting and four action periods (RARARARA). Patients were trained to perform each of the four tasks at the same rate before the scan and at the same rate as during the scan session. Tasks 1 and 3 were part of the reeducational procedure for all patients. Before scanning, the experimenter checked visually and by touch that no contraction was clinically detectable in the muscles, while patients were practicing tasks 1 and 3. Similarly, during scanning, the experimenter watched whether any sign of contraction was visible on the patients arm while performing tasks 1 and 3. No contractions were observed. The experimenter held the hand corresponding to the moving arm or the imaginary moving arm during the four tasks. The patient was informed of his task through earphones by a short word (right arm, imagine, ex, or rest). He knew that the two rst sessions were concerned with the injured arm. All patients performed the four tasks in the same order, i.e., tasks 14. Patients 1 and 3 participated in a second-session fMRI scan with the same tasks, 18 months after the rst scan (Table 3).
Functionnal Magnetic Resonance Imaging

Tasks were performed in the following order: 1. Imaginary arm exion: injured arm. The patient was asked to imagine he was exing his injured arm at a rate of exion of every second and a half. He was told not to imagine extension. An experimenter held the patients hand on the side of the imaginary moving arm, in order to keep the stimulations constant across the four conditions. 2. Flexion of the injured arm: the patient was asked to ex the injured elbow. None of the patients were able to initiate a exion in the injured arm without a contraction (adduction or extension) of the preserved arm. All exions were performed with the intention of exing. An experimenter who was holding the patients hand during the four conditions performed the passive
Microsurgery DOI 10.1002/micr

The fMRI scan was performed on a 1.5 tesla (T) clinical magnetic resonance scan system (Philips Gyro-Scan). A head-holder was used to avoid movements of the head. Subjects were instructed to keep their eyes closed and to remain relaxed, avoiding even minimal movement. Short instructions were given by means of earphones.

fMRI Study of Cerebral Plasticity

Table 2. Brain Activity During Executed and Imagined Movements on Healthy Side* Ipsilateral M1 Patients 1 1 2 3 3 6 7 4 5 (rst time) (second time) (rst time) (second time) Y E I E Y Y Y Y Y Y Y Y PMA I Y E Y Y Y Y Y SMA I Parietal E Y Y I E Y Y Y Y Y Y Y Y Y Y Y M1 I Y Y E Y Y Y Y Y Y Y Y Y Contralateral PMA I E Y Y SMA I

305

Parietal E Y Y Y I

Y Y Y

Y Y

Y Y Y Y Y

Y Y

Y Y

Y Y Y Y

Y Y

Y Y Y Y

Y Y

*Presence of activity in areas ipsilateral and contralateral to exion. M1, primary motor area; PMA, premotor area; SMA, supplementary motor; E, effective exion; I, imagined exion; Y, activity present. Cells are empty when task was not performed.

Table 3. Brain Activity During Executed and Imagined Movements on Neurotised Side* Ipsilateral M1 Patients 1 1 2 3 3 6 7 4 5 (rst time) (second time) (rst time) (second time) E Y Y Y Y Y Y Y Y I E Y Y PMA I Y E Y Y SMA I Y E Y Y Y Y Y Y Y Y Y PAR I E Y Y Y M1 I E Y Y Y Contralateral PMA I Y E Y Y SMA I E Y Y Y PAR I Y

Y Y Y Y

Y Y

Y Y Y Y

Y Y Y

Y Y Y Y

Y Y Y

Y Y Y

Y Y Y

Y Y

*Presence of activity in areas ipsilateral and contralateral to exion. M1, primary motor area; PMA, premotor area; SMA, supplementary motor; PAR, parietal areas; E, effective exion; I, imagined exion; Y, activity present. Cells are empty when task was not performed.

Anatomical slices were acquired in T2 turbo spin echo with a 512 3 512 matrix (repetition time, 4,522 ms; echo time, 100 ms; focus of view, 220 mm) in the horizontal plane, parallel to a line joining the anterior commissure and the posterior commissure (CA-CP line). The number of slices per scan was 24; slice thickness was 4 mm. Functional images were acquired using a T2*echoplanar imaging single-shot sequence with a 64 3 64 matrix (repetition time, 3,000 ms; echo time, 100 ms; focus of view, 220 mm) in the horizontal plane, parallel to the CA-CP line. The number of slices per scan were 12; slice thickness was 8 mm (voxel size was 3.5 3 3.5 3 8 mm). Each functional study consisted of a time-course series of 80 scans (total duration, 4 min), alternating four periods of rest and four periods of action. During each period, 10 scans were performed.
Image Analysis

Data were analyzed with statistical parametric mapping (SPM99 software, Wellcome Department of Cognitive Neurology, London, UK), running under Matlab 5.3

(Matchworks, Inc.). Scans were realigned and resliced from the 40th image for each sequence (to control head motion) and transformed into the standard stereotactic anatomical space corresponding to the atlas of Talairach and Tournoux,13 and voxels were smoothed at full width at half maximum. We made a boxcar analysis for all sessions with a T-contrast, and retained only voxels with Zscore >3 and clusters >3, for an uncorrected threshold P < 0.0001 for single-subject analysis. For group analysis for each session across subjects, we used a sample t-test and retained voxels value (Z score) >3 and clusters >3 for an uncorrected threshold P < 0.001. We also made a subtraction analysis between active movement and imaginary movement, in order to isolate the voxels involved in motion without imagination. The functional maps were studied in the Talairach domain.13 Sensorimotor areas were identied by their anatomical location. In order to get a relative measure of each hemispheres involvement in each task, we computed a score of hemispheric activation by adding the activated clusters
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in the motor and parietal areas of each hemisphere. The difference between the activation score in the hemisphere ipsilateral to the movement minus the activation score in the contralateral hemisphere was divided by the sum of the activations in the two hemispheres. A value of l > 0 reveals an activation in the hemisphere contralateral to the movement greater than in the ipsilateral hemisphere; a value of l < 0 means that the activation in the hemisphere ipsilateral to the movement is greater than in the contralateral hemisphere [S(contralateral clusters) S(ipsilateral clusters)]/[S(contralateral clusters) S(ipsilateral clusters)].

with Z-score 3.78; 28, 20 and 64, with Z-score 3.71). The laterality score for this group revealed a dominance of the contralatral hemisphere (l 0.7).
Real Flexion: Neurotized Elbow

RESULTS Real Flexion: Intact Arm

The activated areas are summarized in Table 2. Activations associated with the preserved arm were observed for all patients in the contralateral primary motor area (M1). The coordinates of activations were identical or symmetrical according to the side of the preserved arm across patients. A bilateral activation of premotor areas was observed in all but one patient (P1, in the rst fMRI session). However, the coordinates of the clusters within this area varied from patient to patient. Activation was found in supplementary motor area (SMA) in all patients except P7. Parietal activations were present in all patients except P2. Parietal activation was located in the posterior parietal Broadman areas 5 and 7. In 2 patients (P4 and P7), additional activations were found in anterior parietal areas (Broadman areas 1, 2, and 3). The lateralization scores were positive in 5 of 7 patients, indicating greater activation in the contralateral hemisphere. Among these patients, P6, who is left-handed and whose preserved arm was the left one, showed a positive index. Similarly, 2 right-handed patients whose right arms were preserved had positive scores. In 2 patients (P2 and P3, rst fMRI), scores were weakly negative. It can be concluded that arm exion tends to be correlated with greater activation in the contralateral hemisphere. A group analysis was performed on the 4 right handed patients whose left arm was intact (P1, P2, P3, and P7). A good overlap between the coordinates of their activated areas was observed (uncorrected P 0.001), i.e., right primary motor area: 34, 20 and 62, with Z-score 3.95; right premotor area: 18, 16 and 72, with Z-score 3.80; right anterior parietal areas: 48, 38 and 36, with Z-score 3.90; 42, 10 and 52, with Z-score 3.81; 26, 20 and 54, with Z-score 3.7; 26, 26 and 52, with Z-score 3.29; and right posterior parietal area 5: 8, 32 and 50, with Z-score 3.38). Activation of the cerebral hemisphere ipsilateral to the exion was observed in the left premotor area (14, 14 and 70,
Microsurgery DOI 10.1002/micr

All patients had a contraction of the contralateral arm while exing their neurotized arm, but they all had the intention to ex their neurotized elbow exclusively (Table 3). Patients 1, 2, 4, 6, and 7 showed bilateral rolandic activations with very similar coordinates in both right and left areas. Patient 5 showed contralateral solcus centralis activation only. Patient 3 showed ipsilateral solcus centralis activation only. Premotor activations were bilateral in 4 patients, contralateral in P5, and absent in 2 patients. Localizations of these activations were only partly overlapping across patients. Differences between patients in the coordinates of clusters were also observed for SMA activations, except in patient 5, who showed ipsilateral activation only. Clusters of parietal activation were found in all patients only in the posterior areas. These activations were bilateral in 3 patients, contralateral in P1 and P5, and ipsilateral in P3. Anterior parietal activations were observed in P4 and P8 only, with no relationship with the grafted arm side. The 2 patients with the best exion recovery (P1 and P5) had a particular pattern in that they showed posterior parietal activation in the contralateral side only, and activation in the contralateral insula. In contrast with exion with the preserved elbow, the lateralization scores were massively negative in all patients showing greater activation in the ipsilateral hemisphere. Thus, movements involving neurotization with root C7 were related to a greater activation of the hemisphere controlling C7. We compared the activation pattern observed under exion of the intact arm with that observed under exion of the neurotized arm. Flexion of the neurotized arm is associated with a bilaterally primary motor activation. This is not the case with exion of the intact arm. There is no clear symmetry in the localization of the clusters in each hemisphere during exion of the neurotized arm. Some of the primary motor activations ipsilateral to the neurotized arm might be due to the extension of the contralateral arm. The regions of the primary motor area contralateral to the neurotized arm and activated during exion of the neurotized are close, but not symmetrical to those activated by exion of the preserved arm. Similarly, the locations of activation in the premotor, SMA, and parietal areas are not similar. It seems then that regions involved in movements of the neurotized arm are specic to this new motor program. A group analysis was performed on the 4 righthanded patients (P1, P2, P3, and P8) whose right arms

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were neurotized. A good overlap between the coordinates of their activated areas was observed in the ipsilateral hemisphere (uncorrected P 0.001), i.e., right primary motor area: 22, 34 and 64, with Z-score 3.36; right premotor area: 34, 16 and 68, with Z-score 3.76; right posterior parietal area: 38, 68 and 46, with Zscore 3.24; and SMA area bilaterally: 4, 34 and 50, with Z-score 3.85; 4, 28 and 54, with Z-score 3.23. In these 4 patients, the laterality score revealed a dominance of the ipsilateral hemisphere (l 1).
Changes Across 18-Month Time Interval Between Two fMRIs (P1 and P3)

The laterality score of the group was positive, revealing greater activation in the contralateral hemisphere.
Imagined Flexion: Neurotized Arm

During exion of the preserved arm, P1 showed the same activation pattern of the primary motor area in both scans. In P3, premotor activation was conserved. During exion of the neurotized arm, P1 showed the same activation pattern in the ispsi- and contralateral primary motor areas in the rst and second scans. More variation between the two scans data was observed for activations in the premotor and parietal areas. Despite the stability of the activation pattern in the primary motor area, P1s lateralization score reveals a shift from an ipsilaterally to a contralaterally greater activation. In P3, activations in the ispsi-primary motor area were conserved. In this patient, activation emerged (under the same statistical threshold) in the contralateral premotor area; the negative laterality score decreased but remained negative.
Imagined Flexion: Intact Arm

Four patients performed this task (P1, P3, P6, and P7; Table 2). No visible contraction of the biceps was observed during the imagined exion. Only P3 showed rolandic activation, in the cortex contralateral to the exing arm. In all patients, premotor activity was observed in the cortex contralateral to the exing arm. Bilateral premotor and SMA activations were also observed, but there was no clear similarity between the locations of clusters across patients. Bilateral parietal activation in Broadman area 40 was found in P1 and P6, and contralateral activation of area 40 in P7. P3 did not show any parietal activation. In summary, imagined exion of the preserved arm is correlated with contralateral premotor and parietal activations. The group analysis for the 3 right-handed patients (P1, P3, and P6) conrms the contralateral location of the common activations (uncorrected P 0.001): right premotor area 8 (10, 52 and 40, with Z-score 3.47); right area 44 (36, 14 and 32, with Z-score 3.63; 42, 6 and 32, with Z-score 3.27); bilateral SMA (2, 12 and 56, with Z-score 3.81; 4, 0 and 54, with Z-score 3.32); and right posterior parietal area 7 (38, 46 and 56, with Z-score 3.42). Activation in the central grey nuclei and cerebellum was also observed.

P1, P3, P6, and P7 performed imaginary exion of the injured arm (Table 3). No contraction of the biceps was visually detected during the task. Only P7 showed contralateral rolandic activation. P3 showed rolandic activation in the cortex ipsilateral to the imagined exing arm. Activation clusters were found in the contralateral premotor area for all 4 patients, with a good correlation between coordinates across patients. Premotor activations were bilateral in 3 patients (P1, P3, and P6). Parietal activations were also observed, but with no similarity in location across patients, and no specic lateralization. The lateralization scores were positive in P1, P6, and P7, showing greater activity in the contralateral cortex. P3 showed rolandic ipsilateral activation, and had a negative lateralization score. Imaginary exion of the neurotized arm was related to greater activity in the cortex which originally controlled exion before the accident. Cortical motor programs were somehow still available in the contralateral hemisphere, despite the deprivation of connections with the corresponding arm. Group analysis with right-handed patients P1, P3, and P6 (uncorrected P 0.001) showed activation in the left primary motor area (40, 20 and 60, with Z-score 4.55); right premotor areas (10, 12 and 60, with Zscore 3.66; 18, 12 and 58, with Z-score 4.21); and left posterior parietal area (12, 28 and 54, with Zscore 3.47). The overall laterality score did not reveal any predominance (l 0). The imaginary exion of the neurotized arm involved an activation of the contralateral primary motor area which was not present when the imaginary exion was performed for the intact arm.
Subtractions Analysis: Elbow Flexion Minus Imaginary Elbow Flexion in the Intact Arm

Three patients (P1, P3, and P7) showed rolandic activation contralateral to the target arm. Coordinates were similar across patients, and were similar to the coordinates of rolandic activation during real exion of the same arm. Bilateral premotor activation was observed in 3 patients (P3, P6, and P7). The coordinates of these activations was relatively symmetrical across both hemispheres. In P1, only an ipsilateral premotor activation was observed, in a region partly similar to the activation observed under exion of the same arm. Bilateral parietal clusters were found in P6 and P7. Activation was also present during exion of the same arm. Parietal activation in P3 was localized in the hemisphere ipsilateral to the target arm, as with real exion of this arm. Laterality
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scores were all positive, showing greater contralateral than ipsilateral activity associated with real arm exion. All in all, bilateral, premotor, and posterior parietal clusters, and some contralateral rolandic clusters, were conserved after subtraction, showing that the exion program of the preserved arm involved both hemispheres, while part of the imaginary action involved a more lateralized activity. A group analysis performed with the 3 right-handed patients (P1, P3, and P7) (uncorrected P 0.001) revealed a cluster of activation in the contralateral primary motor area (24, 20 and 62, with Z-score 3.8). A cluster was observed bilaterally in SMA (4, 26 and 56, with Z-score 4.42; 4, 26 and 58, with Z-score 3.88). No premotor activation was common in the group. The laterality score of the group was l 0.12, showing greater activity in the left compared to the right hemisphere.
Subtractions Analysis: Elbow Flexion Minus Imagined Elbow in the Neurotized Arm

area (10, 54 and 66, with Z-score 3.97). Due to the latter activation, the laterality score showed greater activation in the left contralateral hemisphere. However, activation in the other motor regions was essentially ipsilateral. Activated areas in all conditions were summarized in case of patient 1 on Figure 1.
DISCUSSION

Clusters of activation were found in the primary motor area ipsilateral to the target arm in all patients. The coordinates of these clusters were similar across patients. In contrast with this conservation of activation, no primary motor activity was observed in the cortex contralateral to the target arm. Bilateral premotor activities were observed in P6 (left-handed); premotor activity in P7 was ipsilateral, associated with bilateral SMA activity. Parietal activations were found bilaterally in P3 and P6, and ipsilateral activations in P1. The unique cluster in the anterior parietal cortex was observed contralaterally in P3. The laterality score was positive (0.4) for lefthanded patient P7, showing greater contralateral activity. The score was negative for the 3 right-handed patients (P1, P3, and P7), showing greater ipsilateral activity. Subtraction revealed that activities specic to neurotized real exion do not include primary contralateral activities, and include fewer contralateral premotor and parietal activities than when imagined exion is not subtracted. Activation which was not shared by both real and imaginary exion of the neurotized arm, and which was specic to real exion of this arm in the primary motor cortex, was only ipsilateral. Moreover, activation in the contralateral premotor and parietal areas was decreased. This suggests that part of the cortical motor pathway is ipsilateral, while another part (probably more related to attention, preparation, and representation) remains active in the contralateral cortex original. A group study performed on the 3 right-handed patients (P1, P3, and P7) (uncorrected P 0.001) revealed activation in the ipsi- (right) premotor area (32, 2 and 54, with Z-score 3.66) and in the contralateral postero-parietal
Microsurgery DOI 10.1002/micr

The aim of our study was to identify the neural network involved in the recovery of elbow exion after neurotization of the biceps with bers originating from the contralateral C7 root, which were previously involved in contralateral arm extension. In other words, exion performed with a neurotization between the biceps and contralateral C7 root was performed with a cortico-medullar pathway previously used for extension, but intentionally now used for exion. It must be underscored that any excitation of the motor cortex in the arm region, if it is efcient, cannot result in another outcome than contraction of the biceps. Therefore, the main problem for the brain is to nd out how to activate the grafted pathway which was originally activated by the conscious extension of the contralateral arm, by the neural networks involved in conscious exion of the ipsilateral arm. We compared, on the one hand, brain activation associated with exion in the preserved and neurotized arm, and on the other hand, activation patterns associated with real exion with those associated with an imaginary exion of each arm. As expected, when patients performed exion with their good arm, they showed activation in the contralateral primary motor area. In right-handed patients with a preserved right arm, the left motor area was more activated than the right areas (P4 and P5). In right-handed patients with a preserved left arm (P1 and P3), a shift of the laterality score with a dominance of the right hemisphere during exion of the left arm was observed between the rst and the second fMRI scans (36 months after the rst scan, and 38 and 41 months after the accident). Since their accidents, these 2 patients have almost exclusively used their left arms for daily activities. The increase in their cortical laterality scores might be related to the increase in cortical representation of a limb, or may result from extended practice.14 Together with primary contralateral activation during exion of the good arm, clusters of activities were observed bilaterally in the premotor, supplementary motor, and posterior parietal areas. The existence of ipsilateral activities associated with one arm gesture was documented in other studies.15,16 These ipsilateral activations can be related to excitations running in the uncrossed ipsilateral pyramidal descending bers (15% of the bers of the pyramidal tract). These excitatory activations are described

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Figure 1. Images of activations for patient 1 in each condition. Horizontal slices for P1. Top row 1: Healthy left-side movement conditions. Lower row 2: Movement conditions with neurotized right arm with contralateral C7 root. A, elbow exion; B, imagination of elbow exion; C, substraction analysis: exion minus exion imagination. Right hemisphere is represented at top in all images. In color scale, white represents highest action level.

as facilitating activity in the proximal muscle system. Ipsilateral activations might also be related to cortico-cortical connections through the corpus callosum between sensorimotor and SMA among both hemispheres.17 As expected, exion of the neurotized elbow is correlated with an activation of the ipsilateral primary motor area (contralateral to the rescuing C7 root). The activated region is located similarly across right- and left-handed patients. The activation found bilaterally in the SMA might correspond to cooperation between the hemispheres in the program and control of exion. This collaboration might be mediated by the corpus callosum.18,19 Patients perform an extension adduction contralateral movement in order to elicit a exion in their neurotized elbow. As a whole, this combined gesture might be taken as an asymmetrical collaboration pattern between arms. It was shown that neurotizations between intercostal bers and biceps result in a relocalization or the motor command in the primary cortex.20 Our results conrm, with crossed grafts, that the phenomenon can take place at different levels of integration of neural connections. Imaginary exion of the preserved arm was related to contralateral activity in the associative areas. However, bilateral activation in primary areas M1 and S1, SMA, and premotor cortex was demonstrated by other studies in imaginary movement. By contrast, imaginary exion with the neurotized elbow was correlated with activation in the contralateral primary motor cortex, which is the

original cortex. This might mean that despite total disruption of connections between the motor cortex and the corresponding arm, a cortical neural network in the motor cortex can still be activated by the imagination of a movement. This result is in agreement with other studies.21 The activation within the original contralateral cortex associated with an imagined exion of the neurotized elbow might in fact result from the decrease of inhibition due to deprivation of connections with the neurotized arm.22 When the activation pattern involved in an imaged exion, which is intended and a representation of a exion, is subtracted from the real exion, it cancels the primary contralateral motor activations completely. Therefore because of the participation of the primary contralateral areas it seems to be common to the imaginary and real exion. The exion commanded by the grafted elbow seems to include coordination between a direct command of the graft by the primary ipsilateral command and aspects of an intention and a representation of the movement shared by imagined movement. To summarize: the neural network involved in exion of the neurotised elbow includes: ipsilateral pathway in the primary motor cortex, premotor cortex, supplementary motor area, posterior parietal areas, and contralateral networks in the same areas. The localisation of this activation differs depending on the patients. Thus the cortex originally involved in control of the rescued arm still participates in the elaboration and the control of the task through the
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bilateral premotor and primary motor cortex. While the location of ipsilateral activation to the neurotised arm (primary motor, supplementary motor area and parietal) is similar in some patients, the location of contralateral activations are much more variable from patient to patient. The contralateral regions involved in the new movement network do not seem to belong to a network specifically allotted to a given action. These regions perhaps benet from the decrease in inhibition due to a total deafferentiation of the arm22 and from interhemispheric connections. They might be recruited partly according to strategies specic to each patient. These strategies might partly depend on re-education procedures and on the motor skills developed by patients before their accidents.

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Microsurgery DOI 10.1002/micr