Effects of aging on the human motor cortical plasticity studied by paired associative stimulation

OBJECTIVE To test whether the normal aging itself may change the cortical plasticity in human. METHODS Motor-evoked potentials (MEPs) were measured from 48 right-handed healthy volunteers (age 21-79) before and after the paired associative stimulation (PAS), comprising a single electric stimulus to the right median nerve at wrist and subsequent transcranial magnetic stimulation (TMS) of the left primary motor cortex. RESULTS The magnitude of MEP increased by PAS in the young and middle but not in the elderly and its change was negatively correlated with the age. CONCLUSIONS These results suggest that the human M1 shows age-dependent reduction of cortical plasticity. SIGNIFICANCE The reduction of the M1 plasticity may be caused by the attenuated responsiveness of intracortical circuits in the M1 and/or disrupted sensorimotor integration within basal ganglia-thalamocortical loop.

[1]  Gregory F. Molnar,et al.  Short and long latency afferent inhibition in Parkinson's disease. , 2003, Brain : a journal of neurology.

[2]  P. A. Tonali,et al.  Effects of aging on motor cortex excitability , 2006, Neuroscience Research.

[3]  B. Day,et al.  Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses. , 1989, The Journal of physiology.

[4]  Leonid Kopylev,et al.  Age‐dependent changes in the ability to encode a novel elementary motor memory , 2003, Annals of neurology.

[5]  I. Ozaki,et al.  Effects of aging on central conduction in somatosensory evoked potentials: evaluation of onset versus peak methods , 1997, Clinical Neurophysiology.

[6]  P. Rossini,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. , 1994, Electroencephalography and clinical neurophysiology.

[7]  A. Granholm,et al.  The nigrostriatal dopamine system of aging GFRα‐1 heterozygous mice: neurochemistry, morphology and behavior , 2008, The European journal of neuroscience.

[8]  L. Cohen,et al.  Induction of plasticity in the human motor cortex by paired associative stimulation. , 2000, Brain : a journal of neurology.

[9]  T. Mima,et al.  Altered plasticity of the human motor cortex in Parkinson's disease , 2006, Annals of neurology.

[10]  K. Mills,et al.  Responses in small hand muscles from magnetic stimulation of the human brain. , 1987, The Journal of physiology.

[11]  U Ruotsalainen,et al.  Decrease in Human Striatal Dopamine D2 Receptor Density with Age: A PET Study with [11C]Raclopride , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  John H. Martin,et al.  Motor but not sensory representation in motor cortex depends on postsynaptic activity during development and in maturity. , 2005, Journal of neurophysiology.

[13]  L. Cohen,et al.  Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation , 2002, The Journal of physiology.

[14]  W. Kohrt,et al.  Effect of aging. , 2000, Nutrition reviews.

[15]  F. Tecchio,et al.  Age dependence of primary motor cortex plasticity induced by paired associative stimulation , 2008, Clinical Neurophysiology.

[16]  S. Tsuji,et al.  Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation. , 1998, Electroencephalography and clinical neurophysiology.

[17]  Albert Gjedde,et al.  PET Studies of Net Blood—Brain Clearance of FDOPA to Human Brain: Age-Dependent Decline of [18F]Fluorodopamine Storage Capacity , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  T. Maurice,et al.  Effect of aging on brain-derived neurotrophic factor, proBDNF, and their receptors in the hippocampus of Lou/C rats. , 2008, Rejuvenation research.

[19]  S. Rossi,et al.  Clinical neurophysiology of aging brain: From normal aging to neurodegeneration , 2007, Progress in Neurobiology.

[20]  J. Donoghue,et al.  Strengthening of horizontal cortical connections following skill learning , 1998, Nature Neuroscience.

[21]  H. Kita.  Glutamatergic and gabaergic postsynaptic responses of striatal spiny neurons to intrastriatal and cortical stimulation recorded in slice preparations , 1996, Neuroscience.

[22]  Ulf Ziemann,et al.  Suppression of LTP-like plasticity in human motor cortex by the GABAB receptor agonist baclofen , 2007, Experimental Brain Research.

[23]  D. Ruge,et al.  Learning Modifies Subsequent Induction of Long-Term Potentiation-Like and Long-Term Depression-Like Plasticity in Human Motor Cortex , 2004, The Journal of Neuroscience.

[24]  M. Laakso,et al.  Neocortical, hippocampal and septal parvalbumin- and somatostatin-containing neurons in young and aged rats: Correlation with passive avoidance and water maze performance , 1993, Neuroscience.

[25]  J. Kimura.  Long and short of nerve conduction measures: reproducibility for sequential assessments , 2001, Journal of neurology, neurosurgery, and psychiatry.

[26]  T. Mima,et al.  Effect of spatial attention on human sensorimotor integration studied by transcranial magnetic stimulation , 2005, Clinical Neurophysiology.

[27]  H. Wieser,et al.  Effects of aging and sex on middle-latency somatosensory evoked potentials: normative data , 2002, Clinical Neurophysiology.

[28]  J. Rothwell,et al.  The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex , 2008, The Journal of physiology.

[29]  D. Sengelaub,et al.  Alterations in dendritic morphology of frontal cortical neurons after basal forebrain lesions in adult and aged rats , 1995, Brain Research.

[30]  L. Cohen,et al.  A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex. , 2003, Journal of neurophysiology.

[31]  A. Yamashita,et al.  Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate brain: decreased levels of mRNAs during aging , 1997, Brain Research.

[32]  P. Rossini,et al.  Central conduction studies and magnetic stimulation. , 1992, Current opinion in neurology and neurosurgery.

[33]  H. Siebner,et al.  Age-related decrease in paired-pulse intracortical inhibition in the human primary motor cortex , 2001, Neuroscience Letters.