Mechanisms for recovery of motor function following cortical damage
Introduction
The cerebral cortex adapts to changing environmental demands throughout an individual's life. Dendrites and spines branch and proliferate, synapses form and degenerate, and the efficacy of synaptic contacts is modulated within a complex intracortical network. Thus, it is not surprising that after an injury to the cerebral cortex, the structure and function of sensory and motor regions is drastically altered. Limited motor recovery can occur spontaneously after injury to the motor cortex; therefore, it will be interesting to determine which neural mechanisms underlie such recovery. Post-injury plasticity has been documented not only at the molecular, synaptic, cellular, network and systems levels in experimental animals but also many of these plasticity events have been correlated with alterations in cortical function using neuroimaging and stimulation techniques in humans. Basic phenomenology is now giving way to specific hypotheses regarding the mechanisms by which motor function is re-acquired after injury. In this review, we summarize some of the important new findings in this evolving field.
Section snippets
Early demonstrations of post-injury plasticity
Direct evidence that adjacent regions of the cortex are functionally altered after cortical injury can be traced to surface stimulation studies by Glees and Cole [1] in the early 1950s. After a focal injury to the primary motor cortex (M1) thumb representation, the damaged representation reappeared in the adjacent cortical territory. Studies in the somatosensory cortex by Jenkins et al. [2] seemed to parallel these results. However, using intracortical microstimulation (ICMS) techniques,
New insights into the cellular and molecular mechanisms underlying local reorganization
Although studies of representational maps in motor cortex are largely phenomenological, it is now clear that focal cortical injury results in specific neurophysiological and neuroanatomical changes in both adjacent and remote cortical tissue. Structural alterations occur in adult mammalian cortex as a consequence of experience [5]. Not surprisingly, focal cortical injury results in local neuroanatomical changes. Between three and 14 days after cortical infarction, rats demonstrate increased
Plastic events remote from the cortical injury
Mammalian brains are endowed with a rich intracortical network that enables reciprocal communication among the various sensory and motor areas. Injury to motor cortex causes potent disruption of integrated sensorimotor networks, resulting in loss of fine motor control [23]. For example, M1 normally receives substantial input from somatosensory cortex, conveying proprioceptive and cutaneous information that is presumably integrated with motor output commands in M1. These somatosensory inputs
Re-emergence of the mass action principle
More than 75 years ago, Lashley [44, 45] postulated his classic theories regarding the relationship between cerebral mass and behavioral change. According to his hypothesis, lesion volume is generally assumed to be associated with the severity of deficits, whereas lesion location is related to the specificity of deficits. Frost et al. [28] recently demonstrated that the PMv DFL expands linearly with respect to the size of the M1 injury. An interpretation formed on the basis of Lashley's
Is there a sensitive period for post-injury plasticity and recovery potential?
One of the most crucial questions that must be addressed by basic research is whether there is a period of time after cortical injury in which the remaining, intact system is more amenable to rehabilitative interventions, through drugs [49, 50, 51], electrical stimulation [52, 53, 54], behavior (physiotherapy) or some combination of treatments. The time-dependent cascade of events in peri-infarct and remote areas would suggest that neuroplasticity mechanisms have a long time course, although
Conclusions
Injury to the motor cortex results in a potent disruption of coordinated networks and their underlying emergent properties, resulting in loss of fine motor control, and the employment of compensatory movement strategies. It now appears that such a disruption to the cortical motor network triggers a major reassembly of inter- and intra-areal cortical networks. Post-injury behavioral experience appears to be crucial to the reassembly of adaptive modules. Recent data suggest that the basic
Update
Although several recent studies have demonstrated that SVZ progenitor cells migrate to the site of injury, substantial growth of new neural tissue has not been observed. However, in a new study in rats, Kolb et al. [61•] found that following cortical injury and subsequent therapeutic treatment, the injury cavity became filled with cells that stain positively for neuronal antigens. These events were correlated with significantly improved behavioral recovery. This study is remarkable as it
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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