functional brain mapping of plasticity in nerorehabilitation · 2014. 10. 15. · korean brain...
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KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Functional Brain Mapping of Plasticity in Nerorehabilitation
Yun-Hee Kim, MD, PhDDepartment of Physical Medicine and Rehabilitation,
Brain-Neurorehabilitation Research Lab.College of Medicine Pochon CHA University
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Understanding the mechanism of plasticity after brain injuryTherapeutic interventions promoting adaptive/successful plasticity
Specific training methodsPhysical methods (electrical/magnetic) Medications
Issues in Neurorehabilitation
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Motor Learning & Plasticity-Functional Remodeling of the Hand Representation in M1
after Stroke in Monkey-Nudo RJ, 1997, 2001
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Changes in Neuronal Morphology after Motor Skill Learning
Increased dendriticbrenchingIncreased Increased dendriticdendriticbrenchingbrenching
Increased dendriticspine densityIncreased Increased dendriticdendriticspine densityspine density
Increased perforated synapsesIncreased Increased perforated synapsesperforated synapses
Increased multiple synaptic boutonIncreased multiple Increased multiple synaptic synaptic boutonbouton
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Functional MRI Evidence for Adult Motor Cortex Plasticity during Motor Skill Learning
Karni et. al., Nature 1995
19 pixels 31 pixels
Control subject Trained subject
Plasticity and Reorganization of Motor Network
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
•Mechanism of motor recovery
•Effect of specific training on reorganization of motor system (training-induced reorganization)
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
1) Perilesional reorganization
2) Ipsilateral motor pathway
3) Supplementary motor or other brain areas
Possible Motor Recovery Mechanisms after Brain Injury
Cramer SC et. al., Stroke 1997
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3
2
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Mapping Plasticity after StrokeCramer et. al, Neurophamacology 2000
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Combined fMRI & TMS Study in the Patients with Recovered Paralytic Upper Limb
Eight patients with hemiparesis (7 stroke, 1 traumatic), 7 male & 1 femaleMean age: 49.4 years (8-70)Mean modified Edinburgh score: +100Mean post-onset duration: 18.6 months (4-35) Brain mapping with both fMRI & TMSMotor activation task: active grasping vs. rest
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Bilateral Cortical Activation in fMRI (5/8: 62.5%)
Case 1R L
Case 2R L
Ipsilateral motor pathway confirmed by TMS
Lt
Rt
Stimulation: Rt motor cortex
MMT/FMA=51.5/56.5MMT/FMA=51.5/56.5
Case 6R L
Case 4R L
Case 5R L
Lt
Rt
Stimulation: Rt motor cortex
Only contralateral motor pathway confirmed by TMS
MMT/FMA=62.4/56.7MMT/FMA=62.4/56.7
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Unilateral Cortical Activation in fMRI (3/8: 37.5%)
Ipsilateral activationIpsilateral activationIpsilateral motor pathway
confirmed by TMS
Lt
Rt
Stimulation: Rt motor cortex
Case 3R L
MMT/FMA=59.6/61
Contralateral activationContralateral activationContralateral motor pathway
confirmed by TMS
Lt
Rt
Stimulation: Lt motor cortex
Case 7R L
Case 8R L
MMT/FMA=62.5/64
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Summary of fMRI & TMS Study
Ipsilateral pathway confirmed: 3/8 (37.5%)Congruency ratio: 5/8 (62.5%)Reasons of discripancy between modalities
Associated (mirror) movement during fMRI (1 case)Increased TMS threshold of ipsilateral pathwayContribution of ipsilateral cortex may be
Not directly from the corticospinal pathwayBut through the polysynaptic pathways such as corticoreticulospinal or transcallosal tracts
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
32 32 Patients with Cerebral Infarct Patients with Cerebral Infarct Mean age 54 y-o (29-70), M/F : 29/3
Inclusion CriteriaInclusion CriteriaLess than PLess than P-- grade of finger extensor at onsetgrade of finger extensor at onsetRevoveryRevovery period : more than 1 monthperiod : more than 1 monthBrain MRI : focal lesion on the Brain MRI : focal lesion on the corticospinalcorticospinal tracttractfMRI : at maximum recovery ( minimum 6 months elapsed)fMRI : at maximum recovery ( minimum 6 months elapsed)
Reorganization of Motor System According to the Lesion Location
Classification of lesionClassification of lesion1. Cerebral Cortex (4)1. Cerebral Cortex (4)
2. Corona 2. Corona RadiataRadiata (17)(17)
3. Posterior Limb of Internal Capsule (6)3. Posterior Limb of Internal Capsule (6)
4. Brainstem (5)4. Brainstem (5)
123
4
Jang SH, Youngnam Univ., 2002
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Region of Interest (ROI)Primary Sensori-Motor Cortex (1)Premotor Cortex (2)Supplementary Motor Area (3)
Results of Normal Subjects
12
3
17 normal subjects / 34 hands32 hands : contralateral SM1 (A) 2 hand : bilateral SM1 (B)4 hand : bilateral SMA (C)
A B C
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Cerebral Cortical Lesion
4 patientsRecovery Mechanism
perilesionalperilesionalreorganization (100%)reorganization (100%)
Hand function•• Grade 4 (2/4, 50%)Grade 4 (2/4, 50%)• Grade 3 (1/4, 25%)• Grade 2 (1/4, 25%)
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Corona Radiata Lesion17 patientsRecovery Mechanism
Bilateral motor cortex Bilateral motor cortex activation (11/17, 65%)activation (11/17, 65%)Contralateral motor cortex activation (6/17, 35%)
Hand function• Grade 4 (2/17, 12%)• Grade 3 (1/17, 6%)• Grade 2 (4/17, 24%)• Grade 1 (10/17, 58%)
2
8
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Posterior Limb Lesion
6 patientsRecovery Mechanism
Bilateral motor cortex activation Bilateral motor cortex activation (100%)(100%)
Hand function• Grade 3 (1/6, 17%)• Grade 2 (1/6, 17%)•• Grade 1 (4/6, 66%)Grade 1 (4/6, 66%)
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Brainstem Lesion
5 patientsRecovery Mechanism
Contralateral motor cortex Contralateral motor cortex activation (3/5, 60%)activation (3/5, 60%)Bilateral motor cortex activation (2/5, 40%)
Hand function•• Grade 4 (3/5, 60%)Grade 4 (3/5, 60%)• Grade 3 (2/5, 40%)
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Summary: Reorganization of Motor Network According to the Lesion Location
Perilesional reorganization to the S1 or PMC is the major mechanism of motor recovery in cortical lesion
Use of ipsilateral motor pathway is the significant mechanism of motor recovery in the subcortical brain lesion but it is less efficient
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Training-Induced Reorganization
Constraint-induced therapy (CIT)Intensive movement trainingTask-oriented trainingCross educationNeurodevelopmental therapyMenral imagery therapy
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CI therapy consists ofCI therapy consists of- Constraint of nonaffected limb- Intensive practice of affected limb 7-8 hours a day for 2-3 consecutive weeks: "massed practice“, “forced use”
Motor evaluationMotor evaluation- MMT, Fugl-Meyer Assessment (FMA) scale, 9 hole peg test - Jebsen hand function test, Hand grasp strength, Sensory test
Constrain methodConstrain method- Custom-designed suit- 8 hrs per day (10 minutes break per each hour)
TrainingTraining- More affected upper extremity- Gross motor activities: ball activities, hockey, etc..- Fine motor activities: writing, peg game, etc.. - ADL training
- Less affected upper extremity during each break time- Strengthening & ROM exercise to avoid disuse
Constraint-Induced Therapy (CIT)
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Constraint Garment & Training
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
50
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66
Before After 2mon. F/U
Case 1
Case 2
Case 3
Case 4
Case 5
50
52
54
56
58
60
62
64
66
Before After 2mon. F/U
Case 1
Case 2
Case 3
Case 4
Case 5
Change of Change of FuglFugl--Mayer Scores Mayer Scores
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
fMRI Changes before and after CIT
Case 1
Case 2
Case 3
Before After
Case 4
Case 5
Newly Newly appeared appeared activation of activation of contralateral contralateral motor/ motor/ premotor premotor cortices cortices after CITafter CIT
Increased activation of Increased activation of ipsilateral motor cortex ipsilateral motor cortex
or SMAor SMA
Before After
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Effect of Intensive Training on Reorganization of Motor Cortex
Clinical Test& fMRI (3T)
Intensive Training5~6 hours/day for 2wksIntensive TrainingIntensive Training5~6 hours/day for 2wks5~6 hours/day for 2wks
Clinical Test& fMRI (3T)with constraint or
without constraintwith constraint orwithout constraint
Gross Motor ActivitiesFine Motor Activities
Occupational Therapy
Gross Motor ActivitiesFine Motor Activities
Occupational Therapy
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
6
16
26
36
46
56
66
Pre Post
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Change of Change of FuglFugl--Meyer Scores Meyer Scores
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
PrePre--TrainingTraining PostPost--TrainingTraining
Patient 1
Patient 2
Increased Activation of Contralateral Motor Cortex (7/8 Cases)
Patient 3
Patient 4
PrePre--TrainingTraining PostPost--TrainingTraining
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
63 202 26 57
118 166 72 182
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Patient 6
Patient 8
Patient 7
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
PrePre--TrainingTraining PostPost--TrainingTraining
Increased Activation of Contralateral Motor Cortex (7/8 Cases)
118 185
0 9
13 100
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Task-oriented Training
• 6 tasks • 40 minutes/day• 4 days/week • For 4 weeks • Practice the same
tasks at home• fMRI and HFT before
and after training
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Demographic and Clinical Data of Patients
14
8
22
12
15
Post
-0.5
0.9
-0.7
-1.0
-1.0
Pre
Lat. Index(affected)
0.6
1.0
1.0
0.6
-0.4
Post
0.9
1
0.7
1
1
Pre
Lat. Index(unaffec.)
Grip Strength
PurduePegboard
1102012Average
14306Rt. Cortical infarct
M/664
1203027Lt. ICHM/333
181010Lt. ICHM/492
18106Rt. Cortical infarct
M/541
PostPrePostPre
1stfMRI
(month)LesionSex/
AgePt.
Changes of Cortical Activation after Task-oriented Training in Chronic Stroke Patients
•Contralateral SMC was newly activated in 2 patients (patients 1, and 2)
•Ipsilateral SMC activity disappeared in 2 patients (patients 3, and 4)
•Ipsilateral PMC (patient 1) and SMA (patient 3) disappeared
•Contralateral PMC was newly activated in patient 2
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Summary: Training-induced Reorganization of Motor Network
Intensive and purposeful motor training induce the reorganization of motor system by
Recruitment of contralateral cortical neural activities as a main mechanismInhibition of ipsilateral pathway
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KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Partial injury Partial injury of CST with of CST with good motor good motor recoveryrecovery
Multimodality Mapping of Motor System: DTI, fMRI, and TMS
Affected
Unaffected 22.5/4.0
23.5/0.3
24.0/0.6
23.9/2.2
Affected
Unaffected
20.3/5.1
21.1/5.0Affected
Unaffected
Sparing of Sparing of CSTCST
Disruption of Disruption of CST: CST:
Bilateral Bilateral cortical cortical
activation in activation in fMRI and fMRI and dispersed dispersed
MEPMEP
Plasticity and Reorganization of Attentional Network
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
The Large Scale Neural Network for Spatial Attention
Attentional network in normal person: frontal, parietal, cingulate gyriKim Y-H, et. al. Neuroimage, 1999
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
0
10
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60
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90
100
Accuracy Response time
* P < .001
*
*
normal patient
(%)
1000
900
800
700
600
500
400
300
200
100
0
(msec)
94.3
51.9
300
512
Behavioral ResultsBehavioral Results of Normal and of Normal and Patient GroupPatient Group
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Cortical Activation in Normal Volunteers (n=11)
Random effect analysis, p<0.001, uncorrected
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Cortical Activation in TBI Patients (n=11)
Random effect analysis, p<0.001, uncorrected
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Difference in Medial Frontal and Cingulate Acvtivation
Normal Group Normal Group TBI PatientsTBI Patients
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Changes in Cortical Activation after Cognitive Rehabilitation Training
PrePre--trainingtraining PostPost--trainingtraining
0
10
20
30
40
50
60
70
80
(%)
800
700
600
500
400
300
200
100
0
(msec)
Accuracy Response time * P < .05
pre post
**505
427
68.556.8
Plastic Changes in AttentionalNetwork after TBI
Impaired cognitive performance was associated with the reorganization of neural network
The most prominent finding: disappearance of cingulateactivation in TBI patients
Additional activation of right inferior frontal gyrus: presumably due to the compensatory hyperactivation for better cognitive performance
Activation of cortical and cingulate network was modulated by short-term cognitive intervention
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Two strategies to recover from post-stroke aphasia
Structural repair of primarily speech-relevant regions (damaged language network)Activation of compensatory areasSMA: most prominent compensatory activation in the subacute stageRestitution of the left STC determine the long-term prognosisRight hemisphere compensation was less effective than the repair of original speech network
Karbe et. Al. Brain and Language, 1998
Brain Plasticity in Poststroke Aphasia
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•Contralateral frontal with small perilesional activation
Mainly Contralateral Frontal Activation in Cortical Injury
•Contralateral frontal activation only
Final language Score: 61.4%
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Bilateral frontal Activation in Subcortical Injury
Final language Score: 71.8%
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Factors Influencing on Reorganization and Language Recovery
Severity of language area damageLesion locationTiming and type of rehabilitationMedications
DopaminergicCholinergic
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
Functional Imaging of Plasticity
Powerful tool for in vivo studyPossible compounds
Performance difference of pre- and post-training status can affect on activationTime of imaging
Initial anxietyHead motionTime-task interaction
KOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUPKOREAN BRAIN MAPPING & PLASTICITY RESEARCH GROUP
ConclusionsHuman brain has capacity of reorganization after injuryWell designed purposeful rehabilitation accelerates efficient reorganization in patients with brain injuryGoal of neurorehabilitation
Maximizing neural plasticity and functional recovery after brain injuryDevelopment of specific therapeutic interventions and combination of therapies to achieve additive or synergistic responses
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AcknowledgementKorean Brain Science and Engineering Research Korean Brain Science and Engineering Research ProgramProgramKorean Scientific and Engineering FoundationKorean Scientific and Engineering FoundationKorean Research FoundationKorean Research FoundationMembers of Korean Brain Mapping & Plasticity Members of Korean Brain Mapping & Plasticity Research Group in Research Group in PochonPochon CHA Univ., CHA Univ., ChonbukChonbukNational Univ., and National Univ., and YoungnamYoungnam UniversityUniversity
SungSung--Ho Jang, MD, PhD, Assistant professorHo Jang, MD, PhD, Assistant professorMyoungMyoung--Hwan Hwan KoKo, MD, PhD, Clinical professor, MD, PhD, Clinical professorSeSe--HoonHoon Park, MDPark, MDSeungSeung--Hun Shin, MDHun Shin, MDJiJi--Won Park, RPT, MSWon Park, RPT, MSHwanHwan--TaekTaek ByunByun, MD, MDYongYong--Hyun Kwon, RPTHyun Kwon, RPTEunEun--HaeHae Jang, MSJang, MSYongYong--Hyun Kwon, RPT, BSHyun Kwon, RPT, BS