Novel hand representations in the human motor cortex after hand allograft.

MOVEMENT IS PROCESSED at multiple levels of the CNS. One key region for motor control is the primary motor cortex (Ml). This area, which sends direct motor commands to muscles via the cortico-spinal pathway, contains a detailed somatotopic map of our body, known as the motor "homunculus. " The concept of homunculus, first described in humans by Penfield (1950), refers to a collection of anatomically and functionally segregated representations of individual body segments along the central sulcus. Although this classical textbook picture of the motor body schema is widely accepted, there is an unresolved controversy regarding how strict this somatotopy is and, related to this issue, whether body parts are represented in Ml as individual muscles or as integrated movements. According to the "muscle" hypothesis, pools of adjacent neurons represent discrete muscles and are organized in a rigid somatotopic manner, while the "movement" hypothesis postulates that the motor map represents motor synergies between several muscle groups. At the root of this controversy are observations made both in human Ml and in its non-human primate homologue, that the same muscle or muscle group can be represented in multiple and sometimes non-adjacent subregions of Ml.Although the functional organization of Ml clearly includes separate representations of face, arm, and leg, recent studies have shown considerable overlap and intermingling of representations of smaller body parts. In monkeys, a single neuron may be active during movements of different digits, and the cortical territories containing neurons active during movements of different digits show considerable overlap (Schieber and Hibbard 1993). Functional Magnetic Resonance Imaging (fMRI) studies in normal subjects confirm the existence of spatial overlap in the motor cortex for movements that involve adjacent corporal segments such as the fingers, wrist, and elbow (Sanes et al. 1995; Lotze et al. 2000). Thus, there seems to be a mosaic-like representation of muscular groups (Sanes et al. 1990; Donoghue et al. 1990), suggesting that body parts are controlled by a distributed network in Ml, probably because it is an efficient way of encoding multi-segment motor synergies (Sanes and Schieber 2001). Recent work in monkeys (Graziano et al. 2006) goes further by showing that long train stimulation can evoke complex, ethologically relevant movements not only in the premotor regions, but also in the primary motor cortex.Data from monkeys and human patients suffering from upper-limb amputation show the great interaction that exists between major representations within the motor area. In non-human primates with accidental amputation of the digits, intracortical microstimulation of Ml in the region normally representing the missing segment yields muscular contractions in the stump and in neighboring areas (Schieber and Deuel 1997; Wu and Kaas 1999). Human studies have likewise shown that the representation of the unaffected muscles expands in such a way that the representation of the arm invades portions of Ml previously dedicated to the amputated hand (Cohen et al. 1991), suggesting that former hand neurons are reassigned to the control of proximal upper limb movements.Interestingly, cortical activation in the primary motor and sensory cortex evidenced in patients able to perform movements of their phantom limbs indicates that the areas devoted to the missing limb are functional, sometimes many decades after amputation (Kew et al. 1994; Lotze et al. 2001; Roux et al. 2003). Phantom movements can be evoked by magnetically stimulating stump muscles representations in M1 (Hess et al. 1986; Cohen et al. 1991; Pascual-Leone et al. 1996; Mercier et al. 2006), and electromyographic recording patterns collected from remaining upper arm muscles while the patient attempts to move the stump clearly depart from movements aimed at the phantom limb (Reilly et al. 2006), indicating that hand motor repertoires still exist in the motor cortex after amputation. …