Pharmacological suppression of plastic changes in human primary somatosensory cortex after motor learning

Abstract. The strict division between motor and somatosensory systems might be less distinct than previously thought. Many brain mapping studies have described changes of somatosensory cortex (S-I) after the execution of a motor task, which supports the idea of a profound interconnectedness in the sensorimotor system. Here we report experiments in which we investigated by means of somatosensory evoked potentials (SSEPs) mapping the reorganizational capacities in primary somatosensory cortex before and after a Hebbian repetitive co-contraction task of the thumb and arm. We investigated the susceptibility of S-I plasticity to the pharmacological modulation of the GABA-neurotransmitter system by application of the GABAA agonist lorazepam. We found that repetitive training induced stable motor learning characterized by a significant improvement of performance. The time differences between the onset of contraction of the deltoid muscle and the abductor pollicis brevis were progressively shortened. The process of motor learning was accompanied by plastic changes in the primary somatosensory cortex as indicated by a significant increase in the dipole strength and a significant shift of the median nerve dipole on the hemisphere contralateral to the exercised side. Moreover, the individual shifts of median nerve dipole location were correlated with the individual improvement in motor performance. After administration of lorazepam, motor learning was significantly suppressed. The behavioural effect was accompanied by an abolition of the N20 dipole shift and an unchanged dipole strength. The results imply that motor learning leads to a profound reorganization in S-I which is subject to pharmacological suppression with the GABA agonist lorazepam.

[1]  M. Merzenich,et al.  Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  S. Kinomura,et al.  Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in humans related to ipsilateral and contralateral hand movement , 1993, Brain Research.

[3]  S. Wise,et al.  Mechanisms of use-dependent plasticity in the human motor cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Prince,et al.  Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and developing rat neocortex. , 1990, Brain research. Developmental brain research.

[5]  Xiaoqin Wang,et al.  Remodelling of hand representation in adult cortex determined by timing of tactile stimulation , 1995, Nature.

[6]  Y. Frégnac,et al.  A cellular analogue of visual cortical plasticity , 1988, Nature.

[7]  E G Jones,et al.  Long-range focal collateralization of axons arising from corticocortical cells in monkey sensory-motor cortex , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Matthias M. Müller,et al.  Perceptual Correlates of Changes in Cortical Representation of Fingers in Blind Multifinger Braille Readers , 1998, The Journal of Neuroscience.

[9]  G. Lynch,et al.  Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex , 1992, Neuroscience.

[10]  U. Eysel,et al.  Proprioception acts as the main source of input in human S‐I activation experiments: a functional MRI study , 1998, Neuroreport.

[11]  M. Hallett,et al.  Rapid plasticity of human cortical movement representation induced by practice. , 1998, Journal of neurophysiology.

[12]  M Kano,et al.  Functional reorganization of adult cat somatosensory cortex is dependent on NMDA receptors. , 1991, Neuroreport.

[13]  L. Cohen,et al.  Cortical excitability changes induced by deafferentation of the contralateral hemisphere. , 2002, Brain : a journal of neurology.

[14]  J P Malin,et al.  Cortical reorganization in patients with facial palsy , 1997, Annals of neurology.

[15]  L. L. Porter Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats , 2004, Experimental Brain Research.

[16]  P. Garraghty,et al.  NMDA receptors and plasticity in adult primate somatosensory cortex , 1996, The Journal of comparative neurology.

[17]  B. Pleger,et al.  Assessment of reorganization in the sensorimotor cortex after upper limb amputation , 2001, Clinical Neurophysiology.

[18]  J. Liepert,et al.  Changes of cortical motor area size during immobilization. , 1995, Electroencephalography and clinical neurophysiology.

[19]  J. Liepert,et al.  Pharmacological modulation of training-induced plastic changes in human motor cortex. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[20]  Hubert R. Dinse,et al.  Associative pairing of tactile stimulation induces somatosensory cortical reorganization in rats and humans , 1996, Neuroreport.

[21]  B. Rockstroh,et al.  Increased Cortical Representation of the Fingers of the Left Hand in String Players , 1995, Science.

[22]  KM Jacobs,et al.  Reshaping the cortical motor map by unmasking latent intracortical connections , 1991, Science.

[23]  L. L. Porter,et al.  Morphological Characterization of a Cortico-cortical relay in the cat sensorimotor cortex. , 1997, Cerebral cortex.

[24]  M. Hallett,et al.  Role of the human motor cortex in rapid motor learning , 2001, Experimental Brain Research.

[25]  W. Singer,et al.  Long-term potentiation and NMDA receptors in rat visual cortex , 1987, Nature.

[26]  E. M. Wilson,et al.  Regional cerebral blood flow comparison of right and left hand movement , 1979, Neurology.

[27]  S. Cruikshank,et al.  Evidence for the Hebbian hypothesis in experience-dependent physiological plasticity of neocortex: a critical review , 1996, Brain Research Reviews.

[28]  A. P. Georgopoulos,et al.  Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness. , 1993, Science.

[29]  B. Pleger,et al.  Repetitive training of a synchronised movement induces short-term plastic changes in the human primary somatosensory cortex , 2001, Neuroscience Letters.

[30]  G. Collingridge,et al.  GABAB autoreceptors regulate the induction of LTP , 1991, Nature.

[31]  Walter Paulus,et al.  The effect of lorazepam on the motor cortical excitability in man , 1996, Experimental Brain Research.

[32]  J. Binder,et al.  Functional magnetic resonance imaging of complex human movements , 1993, Neurology.

[33]  G. Recanzone,et al.  Topographic reorganization of the hand representation in cortical area 3b owl monkeys trained in a frequency-discrimination task. , 1992, Journal of neurophysiology.

[34]  J. Callicott,et al.  Hemispheric control of motor function: a whole brain echo planar fMRI study , 1998, Psychiatry Research: Neuroimaging.

[35]  H. Burton,et al.  Quantitative measurements of receptive field changes during antagonism of GABAergic transmission in primary somatosensory cortex of cats , 2004, Experimental Brain Research.

[36]  H. Dinse,et al.  Shifts in cortical representations predict human discrimination improvement , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Hallett,et al.  Reorganization in motor cortex in amputees and in normal volunteers after ischemic limb deafferentation. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[38]  Á. Pascual-Leone,et al.  Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. , 1993, Brain : a journal of neurology.

[39]  Mark Hallett,et al.  The role of reading activity on the modulation of motor cortical outputs to the reading hand in braille readers , 1995, Annals of neurology.

[40]  R. Oostenveld,et al.  Increased auditory cortical representation in musicians , 1998, Nature.

[41]  J. Liepert,et al.  Motor plasticity induced by synchronized thumb and foot movements , 1999, Experimental Brain Research.

[42]  D. O. Hebb,et al.  The organization of behavior , 1988 .