Effects of sensorimotor deprivation on human cortical excitability and motor learning Restricted; Files Only

Abstract

Synaptic strengthening, specifically long-term potentiation- (LTP)-like plasticity in primary motor cortex (M1) underlies the ability to learn complex motor skills. Understanding how to enhance the capacity for LTP-like plasticity in M1 is necessary to improve recovery for individuals with motor deficits, such as after stroke. While long-term disuse of a limb has been shown to have maladaptive structural and functional consequences, short-term immobilization of the arm has shown promise as a low-cost method to enhance the capacity for LTP-like plasticity in M1. However, the specific synaptic changes that underlie this enhanced capacity for plasticity after immobilization, as well as its behavioral effects, remain poorly understood. This dissertation investigates the changes in cortical excitability that occur after short-term immobilization and the effect of immobilization on acquisition and consolidation of a novel sequence-specific motor skill. We replicated previous findings by demonstrating that immobilization decreased corticospinal excitability (CSE) in, and increased interhemispheric inhibition (IHI) onto, the hemisphere associated with the immobilized limb, but a significant change in intracortical inhibition was not observed at the group level. However, our results revealed that decreased CSE was significantly correlated with decreased GABAA-ergic intracortical inhibition only in the immobilization group. Previous research has demonstrated that decreases in GABAA-ergic inhibition are necessary for induction of LTP-like plasticity in M1; therefore, decreased intracortical inhibition after short-term arm immobilization may provide a novel mechanism to enhance the capacity for LTP-like plasticity within M1. Additionally, we examined the effect of short-term immobilization on two stages of motor learning, skill acquisition and consolidation, using a modified version of the Serial Reaction Time Task (SRTT). While task performance improved during training across participants, skill improvement was not sequence-specific, and there was not a significant effect of immobilization on acquisition or consolidation of SRTT skill. However, we hypothesize that immobilization is more likely to influence performance and learning on a task that requires proprioceptive feedback or multi-joint coordination. Taken together, our results suggest that while short-term immobilization of the arm modulates neurophysiological markers of plasticity in M1, it does not influence performance or learning on a motor task that involves individuated, sequenced finger movements.

Table of Contents

Table of Contents

CHAPTER 1: GENERAL INTRODUCTION 1

1.1 ABSTRACT 2

1.2 INTRODUCTION 3

1.3 THE ROLE OF M1 IN GOAL-DIRECTED HAND MOVEMENTS 5

1.3.1 M1 Involvement in Movement Execution 5

1.3.2 M1 Plasticity and Sensorimotor Learning 9

1.4 THE ROLE OF SENSORY REGIONS IN GOAL-DIRECTED HAND MOVEMENTS 13

1.4.1 Posterior Parietal Cortex (PPC) as a Sensorimotor Integration Hub 13

1.4.2 Primary Somatosensory Cortex Involvement in Sensorimotor Integration 15

1.5 IMPACT OF STROKE ON SENSORIMOTOR INTEGRATION AND LEARNING 19

1.5.1 Sensorimotor Deficits after Stroke 19

1.5.2 Plasticity and Sensorimotor Learning after Stroke 21

1.6 STRATEGIES TO MODULATE SENSORIMOTOR INTEGRATION AND POTENTIAL THERAPEUTIC EFFECTS AFTER STROKE 24

1.6.1 Current Therapeutic Interventions 24

1.6.2 Future Directions for Therapeutic Interventions 26

1.7 GAP IN KNOWLEDGE 28

1.8 DISSERTATION OVERVIEW 30

CHAPTER 2: SHORT-TERM ARM IMMOBILIZATION MODULATES EXCITABILITY OF INHIBITORY CIRCUITS WITHIN, AND BETWEEN, PRIMARY MOTOR CORTICES 32

2.1 ABSTRACT 33

2.2 INTRODUCTION 34

2.3 MATERIALS AND METHODS 38

2.3.1 Participants 38

2.3.2 TMS Assessments of Intra- and Inter-cortical Excitability 39

2.3.3 Arm Immobilization 40

2.3.4 MEP Analysis and Statistical Approach 41

2.4 RESULTS 42

2.4.1 Activity Monitoring 42

2.4.2 Resting Motor Threshold (RMT) 43

2.4.3 Corticospinal Excitability (CSE) 43

2.3.4 Interhemispheric Inhibition (s-IHI & l-IHI) 44

2.3.5 Intracortical Inhibition (SICI & LICI) 45

2.3.6 Bivariate Correlations 48

2.5 DISCUSSION 49

2.6 CONCLUSIONS 54

CHAPTER 3: EFFECTS OF SHORT-TERM IMMOBILIZATION ON MOTOR SKILL ACQUISITION 55

3.1 ABSTRACT 56

3.2 INTRODUCTION 56

3.3 MATERIALS AND METHODS 58

3.3.1 Study Participants 59

3.3.2 Motor Task Paradigm 59

3.3.3 Arm Immobilization 60

3.3.4 Motor Skill Acquisition Paradigm 61

3.3.5 Behavioral Outcome Measures 61

3.3.6 Assessment of general motor performance 62

3.3.7 Assessment of sequence-specific skill 63

3.3.8 Associations between behavioral and neurophysiological measures 64

3.4. RESULTS 64

3.4.1 Assessment of general motor performance 65

3.4.2 Assessment of sequence-specific skill 67

3.4.3 Associations between behavioral and neurophysiological measures 69

3.5 DISCUSSION 69

3.5.1 Immobilization does not influence general motor performance on the SRTT 70

3.5.2 Acquisition of sequential, individuated finger movements is not preferentially enhanced after immobilization 71

3.5.3 Task characteristics may influence the effects of immobilization 71

3.5.4 Skill improvements across groups were not sequence-specific 73

3.5.5 Study limitations 74

3.6 CONCLUSIONS 74

CHAPTER 4: SHORT-TERM IMMOBILIZATION OF THE ARM DOES NOT MODIFY CONSOLIDATION OF SKILLED FINGER MOVEMENTS 76

4.1 ABSTRACT 77

4.2 INTRODUCTION 77

4.3 METHODS 79

4.3.1 Study Participants 79

4.3.2 Motor Task Paradigm 80

4.3.3 Arm Immobilization 81

4.3.4 General Motor Performance 81

4.3.5 Sequence-specific skill 82

4.3.6 Associations between behavioral and neurophysiological measures 82

4.4 RESULTS 82

4.4.1 Activity Monitoring 83

4.4.2 General Motor Performance 84

4.4.3 Sequence-specific skill 86

4.4.4 Associations between behavioral and neurophysiological measures 87

4.5 DISCUSSION 88

4.5.1 Consolidation of sequential, individuated finger movements is not enhanced after immobilization 89

4.5.2 Sequence-specific skill did not improve after training and was not influenced by immobilization 92

4.5.3 Study limitations 93

4.6 CONCLUSIONS 94

CHAPTER 5: DISCUSSION 95

5.1 SUMMARY OF RESULTS 96

5.2 IMMOBILIZATION AS A METHOD TO ENHANCE MOTOR LEARNING 100

5.3 IMPLICATIONS FOR CLINICAL TRANSLATION 102

5.4 METHODOLOGICAL CONSIDERATIONS FOR SHORT-TERM IMMOBILIZATION 104

5.5 UTILIZATION OF THE SRTT TO ASSESS BEHAVIORAL EFFECTS OF SHORT-TERM IMMOBILIZATION 106

5.6 LIMITATIONS 108

5.7 CONCLUSIONS 110

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Neuroscience
Keyword	Motor Learning Sensorimotor Deprivation Cortical Excitability
Committee Chair / Thesis Advisor	Borich, Michael, Emory University
Committee Members	Ting, Lena, Emory University Field-Fote, Edelle, Emory University Prinz, Astrid, Emory University Sober, Samuel, Emory University

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