Effects of rehabilitative training on recovery of hand motor function: A review of animal studies

Neuromotor systems have the capacity for functional recovery following damage to the central nervous system. This recovery can be enhanced by rehabilitative training. Animal studies in which artificial damage is induced in a specific region of the brain or spinal cord of rodents or monkeys have contributed to our understanding of the effects of rehabilitative training. In this article, I provide an overview of recent studies in which experimental animals were used to investigate the effects of rehabilitative training on motor recovery and brain plasticity. A study from my group in the macaque monkey reported the effects of hand motor training on motor recovery after lesioning of the primary motor cortex (M1) or the corticospinal tract at the cervical level. In monkeys that had undergone extensive post-lesion training, manual dexterity recovered to previous levels. Rehabilitative training was more effective in promoting recovery of manual dexterity when initiated immediately after the corticospinal tract lesion rather than 1 month later. Both functional brain imaging and gene expression analyses suggest that functional and structural changes may occur in undamaged motor areas during recovery of hand function after M1 or corticospinal tract lesions.

[1]  Aryeh Routtenberg,et al.  GAP-43: an intrinsic determinant of neuronal development and plasticity , 1997, Trends in Neurosciences.

[2]  S. Sasaki,et al.  Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation. , 2004, Journal of neurophysiology.

[3]  J. Winn,et al.  Brain , 1878, The Lancet.

[4]  J. Bloch,et al.  Progressive plastic changes in the hand representation of the primary motor cortex parallel incomplete recovery from a unilateral section of the corticospinal tract at cervical level in monkeys , 2004, Brain Research.

[5]  S. Rothman,et al.  Glutamate neurotoxicity in vitro: antagonist pharmacology and intracellular calcium concentrations , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  O. Witte,et al.  Effects of rehabilitative training and anti-inflammatory treatment on functional recovery and cellular reorganization following stroke , 2012, Experimental Neurology.

[7]  R Langton-Hewer,et al.  The hemiplegic arm after stroke: measurement and recovery. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[8]  T. Isa,et al.  A subcortical oscillatory network contributes to recovery of hand dexterity after spinal cord injury , 2009, Brain : a journal of neurology.

[9]  Dawn L. Merrett,et al.  Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery. , 2007, Brain : a journal of neurology.

[10]  D. Corbett,et al.  Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury , 2004, The Journal of Neuroscience.

[11]  M. Molinari,et al.  Utility of delayed spinal cord injury rehabilitation: an Italian study , 2006, Neurological Sciences.

[12]  V. Perry,et al.  The long-term effects of removal of sensorimotor cortex in infant and adult rhesus monkeys. , 1983, Brain : a journal of neurology.

[13]  Randolph J. Nudo,et al.  Behavioral and neurophysiological effects of delayed training following a small ischemic infarct in primary motor cortex of squirrel monkeys , 2006, Experimental Brain Research.

[14]  S. Gilman,et al.  Lesions of the Precentral Gyrus in Nonhuman Primates: A Pre-Medline Bibliography , 2002, International Journal of Primatology.

[15]  T. Isa,et al.  Effects of early versus late rehabilitative training on manual dexterity after corticospinal tract lesion in macaque monkeys. , 2013, Journal of neurophysiology.

[16]  H. Kuypers A new look at the organization of the motor system. , 1982, Progress in brain research.

[17]  J. Denny Molecular mechanisms, biological actions, and neuropharmacology of the growth-associated protein GAP-43. , 2006, Current neuropharmacology.

[18]  Adam R. Ferguson,et al.  Extensive Spontaneous Plasticity of Corticospinal Projections After Primate Spinal Cord Injury , 2010, Nature Neuroscience.

[19]  H. Onoe,et al.  Time-Dependent Central Compensatory Mechanisms of Finger Dexterity After Spinal Cord Injury , 2007, Science.

[20]  B. Alstermark,et al.  Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons. , 2004, Journal of neurophysiology.

[21]  M. Schieber,et al.  Reduced muscle selectivity during individuated finger movements in humans after damage to the motor cortex or corticospinal tract. , 2004, Journal of neurophysiology.

[22]  R. Lemon Descending pathways in motor control. , 2008, Annual review of neuroscience.

[23]  G. Rizzolatti,et al.  Architecture of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey , 1991, The Journal of comparative neurology.

[24]  S. Carmichael,et al.  New Patterns of Intracortical Projections after Focal Cortical Stroke , 2001, Neurobiology of Disease.

[25]  T. Isa,et al.  Differential Expression of Secreted Phosphoprotein 1 in the Motor Cortex among Primate Species and during Postnatal Development and Functional Recovery , 2013, PloS one.

[26]  S. Sasaki,et al.  Direct and indirect cortico-motoneuronal pathways and control of hand/arm movements. , 2007, Physiology.

[27]  A. Yamashita,et al.  Expression of GAP-43 and SCG10 mRNAs in Lateral Geniculate Nucleus of Normal and Monocularly Deprived Macaque Monkeys , 2000, The Journal of Neuroscience.

[28]  G. Bonin,et al.  The neocortex of Macaca mulatta , 1947 .

[29]  Jeff Biernaskie,et al.  Enriched Rehabilitative Training Promotes Improved Forelimb Motor Function and Enhanced Dendritic Growth after Focal Ischemic Injury , 2001, The Journal of Neuroscience.

[30]  T. Isa,et al.  Increased expression of the growth‐associated protein 43 gene in the sensorimotor cortex of the macaque monkey after lesioning the lateral corticospinal tract , 2009, The Journal of comparative neurology.

[31]  T. Twitchell The restoration of motor function following hemiplegia in man. , 1951, Brain : a journal of neurology.

[32]  Günther Deuschl,et al.  Hand coordination following capsular stroke. , 2004, Brain : a journal of neurology.

[33]  K. Fouad,et al.  Advantages of delaying the onset of rehabilitative reaching training in rats with incomplete spinal cord injury , 2009, The European journal of neuroscience.

[34]  S. Micera,et al.  Restoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury , 2012, Science.

[35]  A. Kriegstein,et al.  Glutamate neurotoxicity in cortical cell culture , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  G. J. Romanes,et al.  The Neocortex of Macaca mulatta , 1948 .

[37]  H. Onoe,et al.  SPP1 is expressed in corticospinal neurons of the macaque sensorimotor cortex , 2010, The Journal of comparative neurology.

[38]  S. Yamane,et al.  Effects of motor training on the recovery of manual dexterity after primary motor cortex lesion in macaque monkeys. , 2008, Journal of neurophysiology.

[39]  Hui Zhong,et al.  Performance of locomotion and foot grasping following a unilateral thoracic corticospinal tract lesion in monkeys (Macaca mulatta). , 2005, Brain : a journal of neurology.

[40]  S. Barbay,et al.  Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. , 2003, Journal of neurophysiology.

[41]  T. Jones,et al.  Motor Skill Training, but not Voluntary Exercise, Improves Skilled Reaching After Unilateral Ischemic Lesions of the Sensorimotor Cortex in Rats , 2008, Neurorehabilitation and neural repair.

[42]  Peter Langhorne,et al.  Predictors of upper limb recovery after stroke: a systematic review and meta-analysis , 2012, Clinical rehabilitation.

[43]  T. Terashima,et al.  Immunohistochemical detection of calcium/calmodulin‐dependent protein kinase II in the spinal cord of the rat and monkey with special reference to the corticospinal tract , 1994, The Journal of comparative neurology.

[44]  Ann M. Stowe,et al.  Extensive Cortical Rewiring after Brain Injury , 2005, The Journal of Neuroscience.

[45]  G. Wittenberg,et al.  The neural basis of constraint-induced movement therapy , 2009, Current opinion in neurology.

[46]  J. Bloch,et al.  Nogo-A–specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates , 2006, Nature Medicine.

[47]  D. Choi,et al.  Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  D. Pandya,et al.  Architecture and frontal cortical connections of the premotor cortex (area 6) in the rhesus monkey , 1987, The Journal of comparative neurology.

[49]  A. Routtenberg,et al.  A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism, and synaptic plasticity , 1987, Trends in Neurosciences.

[50]  M. Tuszynski,et al.  A form of motor cortical plasticity that correlates with recovery of function after brain injury. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Thierry Wannier,et al.  Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans? , 2007, Nature Medicine.

[52]  R. Nudo,et al.  Neural Substrates for the Effects of Rehabilitative Training on Motor Recovery After Ischemic Infarct , 1996, Science.

[53]  T. Schallert,et al.  Use-Dependent Exaggeration of Brain Injury: Is Glutamate Involved? , 1999, Experimental Neurology.