The study of Hebbian-type repetitive transcranial magnetic stimulation on impaired hand motor function in chronic stroke Pubblico

Abstract

 

More effective stroke motor rehabilitation strategies are needed considering that the majority of the six million stroke survivors in the United States suffer long-term motor impairment. Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to enhance stroke motor recovery; however, high intra-individual variability in the efficacy of current rTMS strategies remains a concern. To move toward the development of more effective rTMS strategies, we studied the effect of a novel form of rTMS, called Hebbian-type rTMS (rTMSHeb), on patients with impaired hand motor function suffering chronic stroke involving the primary motor cortex (M1) and/or the corticospinal tract (CST).

The role of M1 and CST in supporting affected hand function has not been previously studied in humans in great detail. Therefore, to better understand the neural substrates supporting impaired motor function of the distal upper extremity in chronic stroke, we determined the relationship between hand and wrist motor function with M1 and its associated CST (n=18, 10M, 61.78 ± 11.89 years). We report that the magnitude of corticospinal output from M1 of the lesioned hemisphere is most likely associated with the extent of impaired hand, but not wrist, motor function.

Next, the effect of rTMSHeb on training-related motor improvement was determined in a double-blinded, placebo controlled study. Twenty patients suffering chronic stroke completed five days of wrist motor training to improve distal UE motor function and were randomized to receive either rTMSHeb (n=10, 6M, 62.6 ± 12.0 years) or sham (rTMSsham, n=10, 4M, 59.7 ± 10.9 years) during training. Exploratory analysis revealed that rTMSHeb may prolong the retention of training-related hand motor improvement compared to rTMSsham.

In conclusion, by restricting our studied population to patients whose infarct included the primary motor system, we examined the role of the surviving tissue of M1 and CST in supporting hand and wrist motor function after stroke. We conclude that M1 output supports impaired hand function and that targeting M1 with rTMSHeb could be of benefit when considering rehabilitative treatment for patients with chronic stroke of M1 and/or CST.

 

Table of Contents

 

CHAPTER 1:

Introduction.............................................................................................................. 1

1.1 Stroke .................................................................................................................. 2

1.2 Potential outcomes of stroke................................................................................ 2

1.3 Upper extremity motor recovery after stroke....................................................... 3

1.4 Neural substrates supporting motor recovery after stroke .................................. 7

1.5 Cortical motor system ......................................................................................... 8

1.5.1 Primary motor cortex............................................................................................................................ 8

1.5.2 Premotor cortex....................................................................................................................................... 13

1.5.3 Supplementary motor cortex ............................................................................................................ 14

1.5.4 Cingulate motor areas ......................................................................................................................... 15

1.5.5 Parietal cortex ......................................................................................................................................... 17

1.5.6 Descending motor tracts...................................................................................................................... 18

1.7 Function of the primary motor cortex in motor skill acquisition........................ 19

1.8 Function of the primary motor cortex in stroke motor recovery ........................ 22

1.9 Repetitive transcranial magnetic stimulation...................................................... 25

1.10 Limitations of current rTMS interventions ...................................................... 28

1.11 Hebbian-type repetitive transcranial magnetic stimulation .............................. 29

1.12 Summary .......................................................................................................... 30

1.13 Specific Aims.................................................................................................... 31

1.13.1 Specific Aim 1 ....................................................................................................................................... 31

1.13.2 Specific Aim 2 ....................................................................................................................................... 32

 

CHAPTER 2: Reduced output of primary motor cortex may be related to the extent of impaired hand function in chronic stroke * ........................................ 36

2.1 Introduction........................................................................................................ 37

2.2 Materials and methods ...................................................................................... 40

2.2.1 Subjects...................................................................................................................................................... 40

2.2.2 Measures of motor function.............................................................................................................. 41

2.2.3 Measures of M1 and CST function.................................................................................................. 43

2.2.4 Measures of M1 and CST structure................................................................................................ 44

2.2.5 Data analysis........................................................................................................................................... 44

2.2.6 Statistical analysis ............................................................................................................................... 47

2.3 Results................................................................................................................ 49

2.3.1 Measures of motor function.............................................................................................................. 49

2.3.2 Measures of M1 and CST function.................................................................................................. 50

2.3.3 Measures of M1 and CST structure................................................................................................. 51

2.3.4 Association between M1 and CST function and structure................................................... 51

2.3.5 Association between M1 and CST function and function of the distal UE.................... 51

2.3.6 Association between M1 and CST structure and function of the distal UE ............,.... 52

2.4 Discussion ......................................................................................................... 52

2.4.1 Measures of motor function............................................................................................................. 53

2.4.2 Measures of M1 and CST function................................................................................................. 54

2.4.3 Association between M1 and CST function and function of the distal UE................... 55

2.4.4 Measures of M1 and CST structure............................................................................................... 56

2.4.5 Association between M1 and CST structure and function of the distal UE ............... 57

2.4.6 Limitations ............................................................................................................................................ 59

2.5 Conclusions....................................................................................................... 59

 

CHAPTER 3: Hebbian-type repetitive transcranial magnetic stimulation may prolong retention of training-related hand motor improvement in chronic stroke 66

3.1 Introduction....................................................................................................... 67

3.2 Materials and methods ..................................................................................... 70

3.2.1 Subjects.................................................................................................................................................... 70

3.2.2 Experimental design ......................................................................................................................... 71

3.2.3 Motor training ..................................................................................................................................... 71

3.2.4 Repetitive transcranial magnetic stimulation ...................................................................... 73

3.2.5 Magnetic resonance imaging........................................................................................................ 74

3.2.6 Outcome measures ........................................................................................................................... 75

3.2.7 Data analysis....................................................................................................................................... 77

3.2.8 Statistical analysis ........................................................................................................................... 78

3.3 Results............................................................................................................. 79

3.3.2 Distal UE motor function .............................................................................................................. 80

3.3.3 Whole arm motor function .......................................................................................................... 82

3.4 Discussion ....................................................................................................... 84

3.4.1 rTMSHeb may enhance the retention but not acquisition of hand motor skill........ 84

3.4.2 Whole arm motor function improves after wrist motor training .............................. 89

3.4.3 rTMSHeb may enhance the retention but not acquisition of arm motor skill ......... 90

3.4.4 Limitations ......................................................................................................................................... 91

3.5 Conclusions.................................................................................................... 92

CHAPTER 4: Summary and future directions.............................................. 105

4.1 Summary of results ...................................................................................... 106

4.2 Conclusions................................................................................................... 108

 

4.3 Future directions ........................................................................................... 108

References........................................................................................................... 113

 

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Nanoscience
Parola chiave	transcranial magnetic stimulation stroke motor
Committee Chair / Thesis Advisor	Buetefisch, Cathrin, Emory University
Committee Members	Smith, Yoland, Emory University Wolf, Steven, Emory University Sathian, Krish, Emory University Epstein, Charles, Emory University

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