Central adaptation following heterotopic hand replantation probed by fMRI and effective connectivity analysis
Introduction
The control of voluntary movements relies on a network of cortical and subcortical brain regions interacting through excitatory or inhibitory circuits to produce the final output to spinal motor neurons (Gerloff and Andres, 2002, Grefkes et al., 2007, Halsband and Lange, 2006, Rizzolatti and Luppino, 2001). Disruption of the dynamic interplay within this network by injury or pathology, however, may prevent normal motor function and force the central nervous system to adapt by re-organising the existing network architecture. These changes are made possible by the brain's capacities for both functional (modifying computational substrates or mechanisms) and structural (axonal rewiring) plasticity as demonstrated in various animal models (Ding et al., 2005, Nudo et al., 1996, Nudo et al., 2003, Pizzi et al., 2006, Schallert et al., 2000, Schallert et al., 2003).
Probably the most important mechanism for disturbances of cortical networks is the damage and hence incapacitation of participating areas or pathways by, e.g., trauma or stroke. Studies which investigated the plastic changes in the human brain due to such (central) injuries often observed a shift in the functional architecture, with neighboring or homologous areas filling in for the damaged regions (Chollet and Weiller, 1994, Weiller et al., 1992). Important examples for this adaptation include the remapping of somatotopic cortex following circumscribed lesions affecting the corticospinal tract (Ward and Cohen, 2004) or the increased recruitment of the right inferior frontal gyrus in language tasks due to ischemia in Broca's region (Lindberg et al., 2007, Saur et al., 2006, Schaechter et al., 2006). Contrasting our knowledge on the effects of central lesions, less attention has been devoted to the adaptive plasticity of cortical networks following peripheral pathology such as nerve injuries and affections to the respective receptor (sensory epithelium) or effector (muscles) organs. However, the observation of widespread cortical re-organisation in non-congenitally blind subjects (Burton et al., 2002, Burton et al., 2004, Goyal et al., 2006) raises the question about the nature of adaptive changes in cortical motor control following manipulation to its peripheral effectors. In other words, can plastic adaptation of motor networks be observed following changes in the anatomy of joints, muscles and nerves as previously hypothesised for tool use (Johnson-Frey, 2003, Maravita and Iriki, 2004)? Furthermore, do these changes reflect the degree of proficiency in the voluntary use of this non-physiological anatomy?
To address these questions, we investigated two patients following heterotopic hand replantation. Both underwent surgery for malignant soft tissue tumours of the proximal forearm with extensive resection of the affected tissue and subsequent heterotopic re-implantation of the amputated distal forearm (incl. the hand) to the stump of the upper arm (Piza-Katzer et al., 2006, Windhager et al., 1995). Tendons of the finger flexors and extensors were attached to the proximal arm muscles which now initiate finger movements causing a radical change of the peripheral motor effectors. Over time, both patients managed to adapt their motor skills and have regained behaviourally relevant capacities for voluntary hand movements (Piza-Katzer et al., 2006, Windhager et al., 1995).
In the current study, regained hand function and continuing disturbances in motor execution were assessed in these patients by kinematic motion analysis, while changes in cortical activation were revealed by functional magnetic resonance imaging (fMRI). Furthermore, dynamic causal modelling (DCM) was used to demonstrate changes in cortical connectivity representing the central adaptation processes following peripheral hand replantation.
Section snippets
Patients
Both patients investigated in this study (Fig. 1) were diagnosed with malignant soft tissue tumours of the forearm whose radical resection necessitated removal of the elbow joint. However, as neither of the patients consented to upper arm amputation, the procedure generally recommended in such cases, both underwent heterotopic replantation of the amputated distal third of the forearm together with the hand to the stump of the upper arm. The surgical procedure, which has already been described
Behavioural performance in reach-to-grasp movements
Fig. 3 illustrates the traces of vertical wrist position, vertical wrist velocity and grasp aperture over time for 8 consecutive reach-to-grasp movements with the replanted and healthy hand. Both patients showed marked differences between the healthy and replanted hand with smoother and more regular movement traces accompanying the unaffected compared to the replanted hands. In terms of the individual movement components of the reach-to-grasp task, the hand transport (represented by the
Discussion
In this study we used fMRI and dynamic causal modelling to examine the adaptation of the cortical motor network formed by areas M1 (primary motor cortex), PMC (ventral premotor cortex) and SMA (supplementary motor area) in two patients following heterotopic hand replantation. Additional kinematic analysis indicated a general slowing of the various movement components of reach-to grasp movements for the replanted hand, especially for patient GM. In comparison with healthy controls the imaging
Acknowledgments
This Human Brain Project/Neuroinformatics research is funded by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health and the Deutsche Forschungsgemeinschaft (KFO-112), and the Brain Imaging Center West (BMBF 01GO0204).
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