Motor Recovery and Cortical Reorganization after Constraint-Induced Movement Therapy in Stroke Patients: A Preliminary Study

Abstract

Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However, the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor cortical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motor function testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected hand movement of stroke patients (LI = 0.23 ± 0.07) compared to controls (LI unaffected patient hand = 0.65 ± 0.10; LI dominant normal hand = 0.65 ± 0.11; LI nondominant normal hand = 0.69 ± 0.11; P < 0.05) due to trends toward increased ipsilateral motor cortical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT, and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01 ± 0.06; P = 0.077) and 6 months post-intervention (LI = -0.03 ± 0.15). Stroke-affected hand movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor function produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor cortical activation toward the undamaged hemisphere.

Keywords

Stroke Hemiparesis Rehabilitation Magnetic resonance imaging Motor cortex

References

Gresham GE , Duncan PW , Stason WB , et al. Post-stroke rehabilitation. Clinical practice guideline. Washington, DC: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1995.

Duncan P , Goldstein L , Horner R , Landsman P , Samsa G , Matchar D. Similar motor recovery of upper and lower extremities after stroke. Stroke 1994;25:1181-1188.

Nakayama H , Hendrik SJ , Raaschou HO , Olsen TS . Recovery of upper extremity function in stroke patients: the Copenhagen stroke study. Arch Phys Med Rehabil 1994;75:394-399.

Duncan P. Synthesis of intervention trials to improve motor recovery following stroke . Top Stroke Rehab 1997;3:1-20.

Taub E , Miller NE , Novack TA , et al. Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehabil 1993;74:347-354.

Kunkel A , Kopp B , Muller G , et al. Constraint-induced movement therapy for motor recovery in chronic stroke patients. Arch Phys Med Rehabil 1999;80:624-628.

Miltner WHR , Bauder H , Sommer M , Dettmers C , Taub E. Effects of constraint-induced movement therapy on patients with chronic motor deficits after stroke: a replication. Stroke 1999;30:586-592.

Marshall RS , Perera GM , Lazar RM , Krakauer JW , Constantine RC , DeLaPaz RL . Evolution of cortical activation during recovery from corticospinal tract infarction. Stroke 2000;31:656-661.

Pineiro R , Pendlebury S , Johansen-Berg H , Matthews PM . Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke: evidence of local adaptive reorganization? Stroke 2001;32:1134-1139.

10.

Cramer SC , Nelles G , Benson RR , et al. A functional MRI study of subjects recovered from hemiparetic stroke. Stroke 1997;28:2518-2527.

11.

Cao Y , D’Olhaberriague L , Vikingstad EM , Levine SR , Welch KMA . Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. Stroke 1998;29:112-122.

12.

Levy CE , Nichols DS , Schmalbrock PM , Keller P , Chakeres DW . Functional MRI evidence of cortical reorganization in upper-limb stroke hemiplegia treated with constraint-induced movement therapy. Am J Phys Med Rehabil 2001;80:4-12.

13.

Oldfield RC . The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 1971;9:97-113.

14.

Cramer SC , Nelles G , Schaechter JD , Kaplan JD , Finklestein SP . Computerized measurement of motor performance after stroke. Stroke 1997;28:2162-2168.

15.

Fugl-Meyer AR , Jaasko L , Leyman I , Olsson S , Steglind S. The post-stroke hemiplegic patient: a method for the evaluation of physical performance. Scand J Rehabil Med 1975;7:13-31.

16.

Wolf SL , LeCraw DE , Barton LA , Jann BB . Forced use of hemiplegic upper extremities to reverse the effect of learned nonuse among chronic stroke and head-injured patients. Exp Neurol 1989;104:125-132.

17.

Jiang A , Kennedy DN , Baker JR , et al. Motion detection and correction in functional MR imaging. Hum Brain Mapp 1995;3:224-235.

18.

Cohen MS , Bookheimer SY . Localization of brain function using magnetic resonance imaging. Trends Neurosci 1994;17:268-277.

19.

Talairach J , Tournoux P. Co-planar stereotaxic altas of the human brain. Stuttgart, Germany: Thieme Medical Publishers; 1988.

20.

Duvernoy HM . The human brain: surface, three-dimensional sectional anatomy and MRI. New York: Springer-Verlag; 1991.

21.

Gati JS , Menon RS , Ugurbil K , Rutt BK . Experimental determination of the BOLD field strength dependence in vessels and tissue. Magn Reson Med 1997;38:296-302.

22.

Forman SD , Cohen JD , Fitzgerald M , Eddy WF , Mintum MA , Noll DC . Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med 1995;33:636-647.

23.

Xiong J , Gao J-H , Lancaster JL , Fox PT . Clustered pixels analysis for functional MRI activation studies of the human brain. Hum Brain Mapp 1995;3:287-301.

24.

Liepert J , Miltner WH , Bauder H , et al. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett 1998;250:5-8.

25.

Liepert J , Bauder H , Miltner WHR , Taub E , Weiller C. Treatment-induced cortical reorganization after stroke in humans. Stroke 2000;31:1210-1216.

26.

Calautti C , Leroy F , Guincestre JY , Marie RM , Baron JC . Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery. Neuroreport 2001;12:3883-3886.

27.

Weiller C , Ramsay SC , Wise RJS , Friston KJ , Frackowiak RSJ . Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol 1993;33:181-189.

28.

Wittenberg GF , Bastian AJ , Dromerick AW , Thach WT , Powers WJ . Mirror movements complicate interpretation of cerebral activation changes during recovery from subcortical infarction. Neurorehabil Neural Repair 2000;14:213-221.

29.

VanMeter JW , Maisog JM , Zeffiro TA , Hallet M , Herscovitch P , Rapoport SI . Parametric analysis of functional neuroimages: application to a variable-rate motor task. Neuroimage 1995;2:273-283.

30.

Rao SM , Bandettini PA , Binder JR , et al. Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex. J Cereb Blood Flow Metab 1996;16:1250-1254.

31.

Sadato N , Ibanez V , Deiber MP , Campbell G , Leonardo M , Hallet M. Frequency-dependent changes of regional cerebral blood flow during finger movements. J Cereb Blood Flow Metab 1996;16:23-33.

32.

Waldvogel D , van Gelderen P , Kenji I , Hallett M. The effect of movement amplitude on activation in functional magnetic resonance imaging studies. J Cereb Blood Flow Metab 1999;19:1209-1212.

33.

Dettmers C , Fink GR , Lemon RN , et al. Relation between cerebral activity and force in the motor areas of the human brain. J Neurophysiol 1995;74:802-815.

34.

Wexler BE , Fulbright RK , Lacadie CM , et al. An fMRI study of the human cortical motor system response in increasing functional demands. Magn Reson Imaging 1997;15:385-396.

35.

Thickbroom GW , Phillips BA , Morris I , Byrnes ML , Mastaglia FL . Isometric force-related activity in sensorimotor cortex measured with functional MRI. Exp Brain Res 1998;121:59-64.

36.

Cramer SC , Weisskoff R , Schaechter JD , et al. Motor cortex activation is related to force of squeezing. Hum Brain Mapp 2002;16:197-205.

37.

Cramer SC , Nelles G , Schaechter JD , Kaplan JD , Finklestein SP , Rosen BR . A functional MRI study of three motor tasks in the evaluation of stroke recovery. Neurorehabil Neural Repair 2001;15:1-8.

38.

Wasserman EM , Pascual-Leone A , Hallet M. Cortical motor representation of the ipsilateral hand and arm. Exp Brain Res 1994;100:121-132.

39.

Ziemann U , Borgheresi A , Yaseen Z , et al. Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles. J Physiol 1999;518:895-906.

40.

Kopp B , Kunkel A , Muhlnickel W , Villringer K , Taub E , Flor H. Plasticity in the motor system related to therapy-induced improvement of movement after stroke. Neuroreport 1999;10:807-810.

41.

Chen R , Gerloff G , Hallett M , Cohen LG . Involvement of the ipsilateral motor cortex in finger movements of different complexities. Ann Neurol 1997;41:247-254.

42.

Schluter ND , Rushworth MFS , Passingham RE , Mills KR . Temporary interference in human premotor cortex suggests dominance for the selection of movements: a study using transcranial magnetic stimulation. Brain 1998; 121:785-799.

43.

Ehrsson HH , Fagergren A , Jonsson T , Westling G , Johansson RS , Forssberg H. Cortical activity in precision-versus power-grip tasks: an fMRI study. J Neurophysiol 2000;83:528-536.

44.

Ferbert A , Priori A , Rothwell JC , Day BL , Colebatch JG , Marsden CD . Interhemispheric inhibition of the human motor cortex. J Physiol 1992;453:525-546.

45.

Allison JD , Meador KJ , Loring DW , Figueroa RE , Wright JC . Functional MRI cerebral activation and deactivatioin during finger movement. Neurology 2000;54:135-142.

46.

Weiller C , Chollet F , Friston KJ , Wise RJS , Frackowiak RSJ . Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol 1992; 31:463-472.

47.

Caramia MD , Palmieri MG , Giacomimi P , Iani C , Dally L , Silvestrini M. Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke. Clin Neurophysiol 2000;111:1990-1996.

48.

Jones TA , Schallert T. Use-dependent growth of pyramidal neurons after neocortical damage. J Neurosci 1994; 14:2140-2152.

49.

Stroemer RP , Kent TA , Hulsebosch CE . Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke 1995;26:2135-2144.

50.

Jones TA , Chu CJ , Grande LA , Gregory AD . Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J Neurosci 1999;19:10153-10163.

51.

Biernaskie J , Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci 2001;21:5272-5280.