Cortical Excitability in Chronic Stroke and Modulation by Training: A TMS Study

Abstract

Background. A possible role for GABA in regulating cortical plasticity after stroke has been proposed. Objective. To investigate changes in intracortical inhibitory and facilitatory circuits in the affected hemisphere more than 6 months after stroke, as well as modulation of excitability by a single training session. Methods. A total of 22 patients >6 months after stroke were compared to age- and gender-matched healthy participants. Cortical excitability was assessed by transcranial magnetic stimulation (TMS), including paired-pulse stimulation, before and up to 30 minutes after a single 15-minute session of 1 Hz thumb abduction-adduction movements. Results. At baseline, TMS showed decreased intracortical inhibition in the affected hemisphere of patients (P = .004) compared to healthy participants. After training a short-lasting decline in motor evoked potentials was observed in both patients (P = .002) and healthy participants (P = .06). Moreover, in healthy participants, inhibitory activity decreased up to 30 minutes after training whereas no significant change was seen in the patients. Conclusions. The findings indicate that inhibitory intracortical circuits are less active after stroke, and no change in inhibitory activity is evident after a single training session. This may indicate that intracortical disinhibition is beneficial during recovery and that an impaired capacity for modulation remains in the chronic stage of stroke.

Keywords

GABA Neurophysiology Stroke Stroke recovery Transcranial magnetic stimulation

References

Cirstea MC , Levin MF Compensatory strategies for reaching in stroke. Brain. 2000;123:940-953.

Maldonado MA , Allred R. , Felthauser E. , Jones TA Motor skill training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats. Neurorehabil Neural Repair. 2008;22:250-261.

Kleim JA , Hogg TM , VandenBerg PM , Cooper NR , Bruneau R. , Remple M. Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J Neurosci. 2004;24: 628-633.

Nagerl UV , Eberhorn N. , Cambridge SB , Bonhoeffer T. Bidirectional activity-dependent morphological plasticity in hippocampal neurons . Neuron. 2004;44:759-767.

Citri A. , Malenka RC Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharm. 2008;33:18-41.

Jacobs KM , Donoghue JP Reshaping the cortical motor map by unmasking latent intracortical connections . Science. 1991;251:944-947.

Hess G. , Aizenman CD , Donoghue JP Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex. J Neurophysiol. 1996;75:1765-1778.

Cicinelli P. , Pasqualetti P. , Zaccagnini M. , Traversa R. , Oliveri M. , Rossini PM Interhemispheric asymmetries of motor cortex excitability in the postacute stroke stage: a paired-pulse transcranial magnetic stimulation study. Stroke. 2003;34:2653-2658.

Talelli P. , Greenwood RJ , Rothwell JC Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation. Clin Neurophysiol . 2006;117:1641-1659.

10.

Koski L. , Mernar TJ , Dobkin BH Immediate and long-term changes in corticomotor output in response to rehabilitation: correlation with functional improvements in chronic stroke. Neurorehabil Neural Repair. 2004;18:230-249.

11.

Rothwell JC Transcranial electrical and magnetic stimulation of the brain: basic physiological mechanisms. In: Hallett M , Chokroverty S , eds. Magnetic Stimulation in Clinical Neurophysiology. Oxford, UK: Elsevier; 2005:43-60.

12.

Hendricks HT , Zwarts MJ , Plat EF , van Limbeek J. Systematic review for the early prediction of motor and functional outcome after stroke by using motor-evoked potentials . Arch Phys Med Rehabil. 2002;83:1303-1308.

13.

Kujirai T. , Caramia MD , Rothwell JC et al. Corticocortical inhibition in human motor cortex. J Physiol. 1993;471:501-519.

14.

Di Lazzaro V. , Pilato F. , Dileone M. , et al. GABAA receptor subtype specific enhancement of inhibition in human motor cortex. J Physiol. 2006;575:721-726.

15.

Di Lazzaro V. , Pilato F. , Dileone M. , et al. Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: A TMS study . Clin Neurophysiol. 2007;118:2207-2214.

16.

Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. Exp Brain Res. 2004;154:1-10.

17.

Ziemann U. , Chen R. , Cohen LG , Hallett M. Dextromethorphan decreases the excitability of the human motor cortex. Neurology. 1998;51:1320-1324.

18.

Liepert J. , Storch P. , Fritsch A. , Weiller C. Motor cortex disinhibition in acute stroke. Clin Neurophysiol . 2000;111:671-676.

19.

Manganotti P. , Patuzzo S. , Cortese F. , Palermo A. , Smania N. , Fiaschi A. Motor disinhibition in affected and unaffected hemisphere in the early period of recovery after stroke. Clin Neurophysiol. 2002;113:936-943.

20.

Nardone R. , Tezzon F. Inhibitory and excitatory circuits of cerebral cortex after ischaemic stroke: prognostic value of the transcranial magnetic stimulation. Electromyogr Clin Neurophysiol. 2002;42:131-136.

21.

Liepert J. , Haevernick K. , Weiller C. , Barzel A. The surround inhibition determines therapy-induced cortical reorganization . Neuroimage. 2006;32:1216-1220.

22.

Shimizu T. , Hosaki A. , Hino T. , et al. Motor cortical disinhibition in the unaffected hemisphere after unilateral cortical stroke. Brain. 2002;125:1896-1907.

23.

Wittenberg GF , Chen R. , Ishii K. , et al. Constraint-induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabil Neural Repair. 2003;17:48-57.

24.

Liepert J. Motor cortex excitability in stroke before and after constraint-induced movement therapy. Cogn Behav Neurol. 2006;19:41-47.

25.

Wittenberg GF , Bastings EP , Fowlkes AM , Morgan TM , Good DC , Pons TP Dynamic course of intracortical TMS paired-pulse responses during recovery of motor function after stroke. Neurorehabil Neural Repair. 2007;21:568-573.

26.

Manganotti P. , Acler M. , Zanette G. , Smania N. , Fiaschi A. Motor cortical disinhibition during early and late recovery after stroke. Neurorehabil Neural Repair . 2008;22:396-403.

27.

Swayne OB , Rothwell JC , Ward NS , Greenwood RJ Stages of motor output reorganization after hemispheric stroke suggested by longitudinal studies of cortical physiology. Cereb Cortex . 2008;18:1909-1922.

28.

Lazar RM , Fitzsimmons BF , Marshall RS , et al. Reemergence of stroke deficits with midazolam challenge. Stroke. 2002;33:283-285.

29.

Liepert J. , Classen J. , Cohen LG , Hallett M. Task-dependent changes of intracortical inhibition. Exp Brain Res. 1998;118:421-426.

30.

Floyer-Lea A. , Wylezinska M. , Kincses T. , Matthews PM Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning. J Neurophysiol . 2006;95:1639-1644.

31.

Bamford J. , Sandercock P. , Dennis M. , Burn J. , Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521-1526.

32.

Maruyama A. , Matsunaga K. , Tanaka N. , Rothwell JC Muscle fatigue decreases short-interval intracortical inhibition after exhaustive intermittent tasks. Clin Neurophysiol . 2006;117:864-870.

33.

Multicenter trial of hemodilution in ischemic stroke-background and study protocol. Scandinavian Stroke Study Group. Stroke. 1985;16:885-890.

34.

Yozbatiran N. , Der-Yeghiaian L. , Cramer SC A standardized approach to performing the Action Research Arm test. Neurorehabil Neural Repair. 2008;22:78-90.

35.

Bohannon RW , Smith MB Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987 ;67:206-207.

36.

Blicher JU , Nielsen JF Evidence of increased motoneuron excitability in stroke patients without clinical spasticity. Neurorehabil Neural Repair. 2009 ;23:14-16.

37.

Butefisch CM , Wessling M. , Netz J. , Seitz RJ , Homberg V. Relationship between interhemispheric inhibition and motor cortex excitability in subacute stroke patients. Neurorehabil Neural Repair. 2008;22:4-21.

38.

Garry MI , Kamen G. , Nordstrom MA Hemispheric differences in the relationship between corticomotor excitability changes following a fine-motor task and motor learning. J Neurophysiol. 2004;91: 1570-1578.

39.

Blicher JU , Nielsen JF Cortical and spinal excitability changes after robotic gait training in healthy subjects. Neurorehabil Neural Repair. In press.

40.

Renner CI , Schubert M. , Hummelsheim H. Selective effect of repetitive hand movements on intracortical excitability . Muscle Nerve. 2005;31: 314-320.

41.

Duncan PW , Lai SM , Keighley J. Defining post-stroke recovery: implications for design and interpretation of drug trials. Neuropharmacology. 2000;39:835-841.

42.

Ljubisavljevic M. Transcranial magnetic stimulation and the motor learning-associated cortical plasticity. Exp Brain Res . 2006;173:215-222.

43.

Classen J. , Liepert J. , Wise SP , Hallett M. , Cohen LG Rapid plasticity of human cortical movement representation induced by practice . J Neurophysiol. 1998;79:1117-1123.

44.

Butefisch CM , Davis BC , Wise SP , et al. Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci U S A. 2000;97:3661-3665.

45.

Sawaki L. , Yaseen Z. , Kopylev L. , Cohen LG Age-dependent changes in the ability to encode a novel elementary motor memory . Ann Neurol. 2003;53:521-524.

46.

McDonnell MN , Ridding MC Transient motor evoked potential suppression following a complex sensorimotor task. Clin Neurophysiol. 2006;117:1266-1272.

47.

Dobkin BH Fatigue versus activity-dependent fatigability in patients with central or peripheral motor impairments. Neurorehabil Neural Repair. 2008;22:105-110.