Neuroanatomical Substrates for Head Movements in Humans Open Access

Prudente, Cecilia Nasciutti (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/xp68kh06q?locale=en
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Abstract

The neuroanatomical substrates for head movements in humans are not well delineated. It is not clear whether neck muscles are controlled by the ipsilateral or contralateral hemisphere, and the location of the neck motor region in the motor homunculus is still debated. The lack of fundamental information regarding head control is relevant to cervical dystonia (CD), a disorder characterized by involuntary contractions of neck muscles and abnormal head movements. Current understanding of the neuroanatomical basis of CD is very limited. Multiple brain regions have been implicated, but findings across different studies are inconsistent. This thesis addresses the neuroanatomical basis of head movements in normal individuals and in CD using functional magnetic resonance imaging (fMRI) and neuropathology methods. The studies had two main goals: to delineate the neural substrates for normal head movements and to identify abnormalities associated with CD.
The initial studies investigated patterns of brain activity during isometric head rotation with fMRI in healthy volunteers. Significant activation was observed bilaterally in the precentral gyrus, both medial and lateral to the hand area. Next, brain activity was studied in individuals with CD using the same conditions. Analysis of CD data normalized according to the direction of abnormal movements indicated that moving the head in the same direction as the abnormal movements involved more activity in the cerebellum, whereas moving the head in the opposite direction involved more activity in sensorimotor cortical regions. These findings provide evidence of potential cortical and subcortical areas that may be affected in CD. The final studies involved postmortem brain samples of CD cases and age-matched controls to identify neuroanatomical changes associated with CD. Quantitative analyses revealed a significantly lower Purkinje cell density in CD in comparison to controls, suggesting abnormal cerebellar physiology in this disorder.
Collectively, these findings begin to fill a critical gap in the understanding of normal and abnormal head movements in humans. Furthermore, the results may help guide future medical or surgical interventions for CD targeting relevant brain regions, as well as future cellular and animal studies.

Table of Contents

Table of Contents

Chapter 1: Introduction 1
Chapter 2: Imaging the neuroanatomical substrates for normal head movements

2.1. Introduction 5
2.1.1. Directions of head movements 5
2.1.2. Muscles involved in head movements 6
2.1.3. Neuroanatomical substrates for head movements 8
2.1.3.1. Primary motor cortex 8
2.1.3.2. Other brain regions 9
2.1.4. Limitations of studying the neuroanatomical substrates for head movements 11
2.2. Objectives and significance 11
2.3. Materials and methods 12
2.3.1. Participants 12
2.3.2. Magnetic resonance (MR) scanning 12
2.3.3. Experimental design 13
2.3.4. Electromyography 15
2.3.5. Head motion correction 16
2.3.6. Head motion analysis 17
2.3.7. Imaging data analysis 18
2.4. Results 20
2.4.1. Task confirmation 20
2.4.2. Head motion during scans 20
2.4.3. Region of interest (ROI) analysis of hand tasks 23
2.4.4. ROI analysis of head tasks 23
2.4.5. Whole-brain analysis of hand tasks 26
2.4.6. Whole-brain analysis of head tasks 26
2.5. Discussion 30
2.5.1. Is primary motor cortex (M1) control ipsilateral, contralateral or bilateral? 31
2.5.2. Is the neck region in the precentral gyrus medial or lateral? 32
2.5.3. Is the activation in the precentral gyrus M1, dorsal premotor (PMd) or ventral premotor (PMv) cortex? 35
2.5.4. Role of other brain regions 36
2.5.5. Limitations and future studies 37
2.5.6. Conclusions 38

Chapter 3: Imaging the neuroanatomical substrates for head movements in cervical dystonia
3.1. Introduction 39
3.1.1. Dystonia 39
3.1.2. Cervical dystonia: clinical characteristics and epidemiology 41
3.1.3. Anatomical basis of cervical dystonia 42
3.1.4. Neuroimaging studies of cervical dystonia 43
3.1.5. Limitations of neuroimaging studies of cervical dystonia 47
3.2. Objectives and significance 47
3.3. Materials and methods 47
3.3.1. Participants 47
3.3.2. MR scanning 50
3.3.3. Experimental design 50
3.3.4. Electromyography 50
3.3.5. Head motion correction and analysis 50
3.3.6. Imaging data analysis 50
3.4. Results 51
3.4.1. Task confirmation 51
3.4.2. Head motion during scans 52
3.4.3. Within-group analyses for control and cervical dystonia participants 55
3.4.4. Between-groups comparisons for control and cervical dystonia participants 59
3.4.5. Directional preference of torticollis 61
3.5. Discussion 67
3.5.1. Neuroanatomical substrates for head movements in cervical dystonia 67
3.5.2. Direction of head movements and side of torticollis 69
3.5.3. Wrist movements in cervical dystonia 71
3.5.4. Limitations 71
3.5.5. Conclusions and future directions 73

Chapter 4: Neuropathology of cervical dystonia
4.1. Introduction 76
4.2. Objectives and significance 80
4.3. Materials and methods 80
4.3.1. Autopsy material 81
4.3.2. Genetic testing 81
4.3.3. Histological procedures 82
4.3.4. Two-stage analysis 82
4.3.5. Statistical analyses 83
4.4. Results 84
4.4.1. Samples 84
4.4.2. Screening phase 87
4.4.3. Quantification phase 91
4.5. Discussion 94
4.5.1. Limitations of human neuropathology 95
4.5.2. Relevance for classifying the dystonias 99
4.5.3. Inferring causation from clinico-pathological studies 100

Chapter 5: Summary and final conclusions
5.1. Overview 103
5.2. What does greater cerebellar fMRI activation mean? 106
5.3. Is cerebellar involvement due to degeneration or abnormal function? 108
5.4. Is there any other evidence of cerebellar dysfunction in cervical dystonia? 111
5.4.1. Evidence from human studies 111
5.4.2. Evidence from animal studies 113
5.5. How can dysfunction of the cerebellum lead to abnormal head movements in cervical dystonia? 116
5.5.1. Cerebellar intrinsic anatomy 116
5.5.2. Cerebellar connections 116
5.5.3. Cerebellar dysfunction and abnormal head movements 119
5.6. How can the findings be used to guide future studies? 123

References 125
 
Tables and Figures

Chapter 2: Imaging the neuroanatomical substrates for normal head movements
Figure 2.1: Directions of head movements 6
Figure 2.2: Neck muscles involved in head movements 7
Figure 2.3: Representation of the neck region in the motor and sensory homunculi according to different studies 10
Figure 2.4: Experimental design 15
Figure 2.5: Sternocleidomastoid and extensor carpi ulnaris muscles 16
Figure 2.6: Distribution of head motion measurements and their amplitudes for all subjects 21
Figure 2.7: Head movements during rest, hand and head tasks 22
Figure 2.8: Region of interest analysis of the precentral gyrus for isometric wrist extension and head rotation tasks in comparison to rest 23
Figure 2.9: Whole-brain analysis for isometric wrist extension and head rotation tasks in comparison to rest 28
Figure 2.10: Possible location of the medial and the lateral foci identified in our fMRI studies of isometric head rotation 33
Figure 2.11: Stimulation site for contralateral head rotation (left) and other head movements (right) according to Rasmussen and Penfield 34
Table 2.1: Prior reports of the hemisphere controlling head movements in humans 9
Table 2.2: Task confirmation with electromyography 20
Table 2.3: Head motion during scans 22
Table 2.4: Talairach coordinates, maximum t-values, p-values and cluster size for the region of interest analysis 25
Table 2.5: Talairach coordinates, maximum t-values and p-values for whole-brain analyses of hand tasks versus baseline 26
Table 2.6: Talairach coordinates, maximum t-values and p-values for whole-brain analyses of head tasks versus baseline 26

Chapter 3: Imaging the neuroanatomical substrates for head movements in cervical dystonia
Figure 3.1: Types of cervical dystonia 41
Figure 3.2: Distribution of head motion measurements and their amplitudes for control and cervical dystonia groups 53
Figure 3.3: Head movements during rest, hand and head tasks in the cervical dystonia group 54
Figure 3.4: Within and between groups analyses of isometric hand and head tasks in comparison to rest for controls and cervical dystonia 56
Figure 3.5: Blood oxygenation level dependent (BOLD) signal curves for selected sites for the within-group analysis in the cervical dystonia group 57
Figure 3.6: BOLD signal curves for selected sites for the between-group analysis for cervical dystonia versus controls 61
Figure 3.7: Within and between-groups analyses of isometric hand and head tasks in comparison to rest for CDNORM and controls 64
Figure 3.8: Torticollic and non-torticollic directions of isometric head rotation in CDNORM 66
Figure 3.9: BOLD signal curves for selected sites for the contrasts between non-torticollic (blue) and torticollic (orange) directions of head movements in the CDNORM group 66
Table 3.1: Classification of the dystonias according to clinical features 40
Table 3.2: Classification of the dystonias according to etiology 41
Table 3.3: Task-based functional magnetic resonance imaging studies of cervical dystonia 46
Table 3.4: Cervical dystonia participants 49
Table 3.5: Task confirmation with electromyography 52
Table 3.6: Head motion during scans 54
Table 3.7: Talairach coordinates, maximum t-values and p-values for within-group analysis of isometric hand tasks versus baseline in cervical dystonia 57
Table 3.8: Talairach coordinates, maximum t-values and p-values for within-group analysis of isometric head tasks versus baseline in cervical dystonia 58
Table 3.9: Talairach coordinates, maximum t-values and p-values for between-groups analysis of isometric tasks versus baseline in cervical dystonia versus controls 60
Table 3.10: Talairach coordinates, maximum t-values and p-values for between-groups analyses of isometric tasks versus baseline in CDNORM versus controls 65
Table 3.11: Talairach coordinates, maximum t-values and p-values for within-group analysis of isometric head rotation to the torticollic direction versus the non-torticollic direction in CDNORM 67

Chapter 4: Neuropathology of cervical dystonia
Figure 4.1: Histopathology in the midbrain 88
Figure 4.2: Histopathology in the cerebellum 89
Figure 4.3: Box and whisker plot comparing Purkinje cell linear density in 6 cervical dystonia cases and 13 controls 94
Table 4.1: Postmortem studies of cases with CD 77
Table 4.2: Clinical information for CD cases and controls 86
Table 4.3: Main findings of the subjective screening study 90
Table 4.4: Number of nigral inclusions in melanized neurons in the substantia nigra 92

Chapter 5: Discussion and final conclusions
Figure 5.1: Lesions of the cerebellum may cause different phenotypes depending on the nature of the lesion and its consequences 109
Figure 5.2: Anatomical connections of the cerebellum 120
Table 5.1: Some primate studies reported to show dystonic movements of the head 114
Table 5.2: Some smaller mammals reported to have abnormal or dystonic movements of the head 115

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