Susie Henley
University College London, Institute of Neurology, Department Member
Huntington’s disease (HD) is caused by an expanded CAG repeat on the gene encoding for the protein huntingtin. There are conflicting findings about the extent to which repeat length predicts signs of the disease or severity of disease... more
Huntington’s disease (HD) is caused by an expanded CAG repeat on the gene encoding for the protein huntingtin. There are conflicting findings about the extent to which repeat length predicts signs of the disease or severity of disease progression in adults. This study examined the relationship between CAG repeat length and brain volume in a large cohort of pre- and post-motor onset HD gene carriers, using voxel-based morphometry (VBM), an approach which allowed us to investigate the whole brain without defining a priori regions of interest. We also used VBM to examine group differences between 20 controls, 21 premanifest, and 40 early HD subjects. In the 61 mutation-positive subjects higher CAG repeat length was significantly associated with reduced volume of the body of the caudate nucleus bilaterally, left putamen, right insula, right parahippocampal gyrus, right anterior cingulate, and right occipital lobe, after correcting for age. The group contrasts showed significant reduction in grey matter volume in the early HD group relative to controls in widespread cortical as well as subcortical areas but there was no evidence of difference between controls and premanifest subjects. Overall we have demonstrated that increased CAG repeat length is associated with atrophy in extra-striatal as well as striatal regions, which has implications for the monitoring of disease-modifying therapies in the condition.
Research Interests: Neurology, Anterior Cingulate, Magnetic Resonance Imaging, Aging, MRI, and 27 moreMorphometry, Brain, Humans, Caudate Nucleus, Genetic Testing, Female, Voxel Based Morphometry, Male, Huntingtin, Clinical Sciences, Middle Aged, Atrophy, Genotype, Adult, Disease Progression, Huntington disease, Parahippocampal Gyrus, Gray, Voxel, Nuclear Magnetic Resonance Imaging, Genetic Markers, Neurosciences, Region of Interest, Cag, Cohort Studies, Magnetic resonance image, and DNA mutational analysis(Morphometry, Brain, Humans, Caudate Nucleus, Genetic Testing, Female, Voxel Based Morphometry, Male, Huntingtin, Clinical Sciences, Middle Aged, Atrophy, Genotype, Adult, Disease Progression, Huntington disease, Parahippocampal Gyrus, Gray, Voxel, Nuclear Magnetic Resonance Imaging, Genetic Markers, Neurosciences, Region of Interest, Cag, Cohort Studies, Magnetic resonance image, and DNA mutational analysis)
(Morphometry, Brain, Humans, Caudate Nucleus, Genetic Testing, Female, Voxel Based Morphometry, Male, Huntingtin, Clinical Sciences, Middle Aged, Atrophy, Genotype, Adult, Disease Progression, Huntington disease, Parahippocampal Gyrus, Gray, Voxel, Nuclear Magnetic Resonance Imaging, Genetic Markers, Neurosciences, Region of Interest, Cag, Cohort Studies, Magnetic resonance image, and DNA mutational analysis)
Research Interests:
Research Interests:
Therapeutic trials in Huntington's disease (HD) are challenging as clinical progression is slow and variable and reliable biomarkers are lacking. We used magnetic resonance imaging and the brain boundary shift integral to quantify... more
Therapeutic trials in Huntington's disease (HD) are challenging as clinical progression is slow and variable and reliable biomarkers are lacking. We used magnetic resonance imaging and the brain boundary shift integral to quantify whole-brain atrophy rates over 1 year in early and premanifest HD subjects, and controls. Early HD subjects had statistically significantly (P = 0.007) increased (threefold higher) rates of whole-brain atrophy compared with controls. Higher atrophy rates were associated with longer CAG repeat length. MRI-based measures of whole-brain atrophy may have potential as a measure of progression in HD. © 2009 Movement Disorder Society
Research Interests: Cognitive Science, Magnetic Resonance Imaging, MRI, Movement disorders, Brain Mapping, and 13 moreBrain, Humans, Movement, Clinical Sciences, Brain atrophy, Middle Aged, Length, Atrophy, Adult, Disease Progression, Huntington disease, Nuclear Magnetic Resonance Imaging, and Severity of Illness Index
Learning may occur with or without awareness, as explicit (intentional) or implicit (incidental) learning. The caudate nucleus and the putamen, which are affected early in Huntington's disease (HD), are thought to be essential for motor... more
Learning may occur with or without awareness, as explicit (intentional) or implicit (incidental) learning. The caudate nucleus and the putamen, which are affected early in Huntington's disease (HD), are thought to be essential for motor sequence learning. However, the results of existing studies are inconsistent concerning presence/absence of deficits in implicit and explicit motor sequence learning in HD. We assessed implicit and explicit motor sequence learning using sequences of equivalent structure in 15 individuals with a positive HD genetic test (7 premanifest; 8 early stage disease) and 11 matched controls. The HD group showed evidence of normal implicit motor sequence learning, whereas explicit motor sequence learning was impaired in manifest and premanifest HD gene carriers, with progressive decline with progressive disease. Explicit sequence learning may be a useful cognitive biomarker for HD progression. © 2010 Movement Disorder Society
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Research Interests: Magnetic Resonance Imaging, Neuroimmunology, Brain, Humans, Female, and 17 moreNeuroimage, Male, Magnetic Resonance, Young Adult, Clinical Sciences, Head, Aged, Middle Aged, White matter, Adult, Sex Factors, Age Factors, Cortical Thickness, Neurosciences, Region of Interest, Volume Measurement, and Magnetic resonance image
Research Interests:
Research Interests:
Research Interests: Genetics, Neuroscience, Psychology, Clinical Trial, Magnetic Resonance Imaging, and 29 moreImaging, Working Memory, MRI, Family history, Protein Structure and Function, Humans, Genetic Testing, Animals, Functional Imaging, Voxel Based Morphometry, Roi, Mouse Model, Component Analysis, Blood Flow, Degeneration, Biological markers, Huntington disease, Bsi, Sensitivity and Specificity, Brain Function, Clinical Signs, Nuclear Magnetic Resonance Imaging, Diffusion Weighted MRI, Neurosciences, Clinical Diagnosis, Ad, FWHM, Magnetic resonance image, and Clinical Trials as Topic(Imaging, Working Memory, MRI, Family history, Protein Structure and Function, Humans, Genetic Testing, Animals, Functional Imaging, Voxel Based Morphometry, Roi, Mouse Model, Component Analysis, Blood Flow, Degeneration, Biological markers, Huntington disease, Bsi, Sensitivity and Specificity, Brain Function, Clinical Signs, Nuclear Magnetic Resonance Imaging, Diffusion Weighted MRI, Neurosciences, Clinical Diagnosis, Ad, FWHM, Magnetic resonance image, and Clinical Trials as Topic)
(Imaging, Working Memory, MRI, Family history, Protein Structure and Function, Humans, Genetic Testing, Animals, Functional Imaging, Voxel Based Morphometry, Roi, Mouse Model, Component Analysis, Blood Flow, Degeneration, Biological markers, Huntington disease, Bsi, Sensitivity and Specificity, Brain Function, Clinical Signs, Nuclear Magnetic Resonance Imaging, Diffusion Weighted MRI, Neurosciences, Clinical Diagnosis, Ad, FWHM, Magnetic resonance image, and Clinical Trials as Topic)
VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented... more
VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented consistently across studies, and changing user-specified options can alter the results in a way similar to the very biologic differences under investigation.
Research Interests:
Research Interests: Magnetic Resonance Imaging, Prediction, Humans, Caudate Nucleus, Age, and 17 moreFemale, Male, Young Adult, Clinical Sciences, Aged, Middle Aged, Longitudinal Studies, Length, Atrophy, Adult, Retrospective Studies, Disease Progression, Huntington disease, Nuclear Magnetic Resonance Imaging, Mr Imaging, Neurosciences, and Age of Onset
Research Interests: Psychology, Cognitive Science, Emotion, Music, Auditory Perception, and 19 morePsychoacoustics, Experimental Design, Adolescent, Emotions, Musical Instruments, Humans, Female, Male, Young Adult, Quarterly Journal of Experimental Psychology, Aged, Middle Aged, Adult, Age Factors, Older Adult, Logistic Models, Age Groups, Choice Behavior, and Acoustic Stimulation
Research Interests: Psychology, Cognitive Science, Cognition, Magnetic Resonance Imaging, Face, and 20 moreMorphometry, Facial expression, Emotions, Memory, Brain Mapping, Humans, Emotion Recognition, Female, Voxel Based Morphometry, Male, Orbitofrontal cortex, Middle Aged, Emotional Expression, Adult, Analysis of Variance, Neuropsychologia, Huntington disease, Neurosciences, Cognition disorders, and Neuropsychological Tests(Morphometry, Facial expression, Emotions, Memory, Brain Mapping, Humans, Emotion Recognition, Female, Voxel Based Morphometry, Male, Orbitofrontal cortex, Middle Aged, Emotional Expression, Adult, Analysis of Variance, Neuropsychologia, Huntington disease, Neurosciences, Cognition disorders, and Neuropsychological Tests)
(Morphometry, Facial expression, Emotions, Memory, Brain Mapping, Humans, Emotion Recognition, Female, Voxel Based Morphometry, Male, Orbitofrontal cortex, Middle Aged, Emotional Expression, Adult, Analysis of Variance, Neuropsychologia, Huntington disease, Neurosciences, Cognition disorders, and Neuropsychological Tests)
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Huntington's disease (HD) produces progressive and ultimately widespread impairment of brain function. Neostriatal atrophy alone cannot account for whole-brain losses seen postmortem, and the mutant huntingtin protein and its... more
Huntington's disease (HD) produces progressive and ultimately widespread impairment of brain function. Neostriatal atrophy alone cannot account for whole-brain losses seen postmortem, and the mutant huntingtin protein and its neuropathologic sequelae are evident throughout the brain. Whole-brain atrophy quantification encompasses the totality of mutant huntingtin's effects on brain volume and may be useful in tracking progression in trials. We studied whole-brain atrophy in HD using a 2-year follow-up design, with three annual MRI scans. We recruited 20 control subjects, 21 premanifest mutation carriers, and 40 patients with early HD and used the brain boundary shift integral to study rate and acceleration of atrophy. Among subjects with an acceptable quality 2-year scan pair, age- and gender-standardized mean brain atrophy rate was greater (P < 0.001) in the patients with HD (n = 21; 0.88%/yr; 95% confidence interval: 0.62–1.13%/yr) than that in controls (n = 13; 0.16%/yr; 0.00–0.32%/yr). In the 12 patients with early HD in whom acceleration could be directly assessed there was evidence (P= 0.048) of acceleration year-on-year (mean acceleration = 0.69% yr−2; 95% confidence interval: 0.01% yr−2 to 1.37% yr−2), although this was not formally significantly different from that in controls (n = 7, P = 0.055). Statistically significantly increased atrophy rates and acceleration were not seen overall in the premanifest group, who were on average 18 years from predicted disease onset. We conclude that the study of whole-brain atrophy has the potential to inform our understanding of the neurobiology of HD and warrants further study as one means of assessing the outcomes of future clinical trials. © 2009 Movement Disorder Society
Research Interests:
Research Interests: Magnetic Resonance Imaging, Neuroimmunology, Brain, Humans, Female, and 17 moreNeuroimage, Male, Magnetic Resonance, Young Adult, Clinical Sciences, Head, Aged, Middle Aged, White matter, Adult, Sex Factors, Age Factors, Cortical Thickness, Neurosciences, Region of Interest, Volume Measurement, and Magnetic resonance image
Research Interests: Algorithms, Artificial Intelligence, Magnetic Resonance Imaging, Neuroimmunology, Brain, and 13 moreHumans, Caudate Nucleus, Neuroimage, Middle Aged, Atrophy, White matter, Image Enhancement, Adult, Reproducibility of Results, Huntington disease, Large Scale, Sensitivity and Specificity, and Volume change
Research Interests: Emotion, Music, Theory of Mind, Anterior Cingulate, Face, and 26 moreFace recognition (Psychology), Prefrontal Cortex, Neuroimmunology, Emotions, Temporal Lobe, Humans, Cues, Emotion Recognition, Female, Neuroimage, Voxel Based Morphometry, Male, Amygdala, Orbitofrontal cortex, Connectivity, Aged, Middle Aged, Social Functioning, Conceptual Knowledge, Parietal Lobe, Frontotemporal Dementia, Limbic System, Semantic Dementia, Brain Damage, Medial Prefrontal Cortex, and Psychomotor Performance(Face recognition (Psychology), Prefrontal Cortex, Neuroimmunology, Emotions, Temporal Lobe, Humans, Cues, Emotion Recognition, Female, Neuroimage, Voxel Based Morphometry, Male, Amygdala, Orbitofrontal cortex, Connectivity, Aged, Middle Aged, Social Functioning, Conceptual Knowledge, Parietal Lobe, Frontotemporal Dementia, Limbic System, Semantic Dementia, Brain Damage, Medial Prefrontal Cortex, and Psychomotor Performance)
(Face recognition (Psychology), Prefrontal Cortex, Neuroimmunology, Emotions, Temporal Lobe, Humans, Cues, Emotion Recognition, Female, Neuroimage, Voxel Based Morphometry, Male, Amygdala, Orbitofrontal cortex, Connectivity, Aged, Middle Aged, Social Functioning, Conceptual Knowledge, Parietal Lobe, Frontotemporal Dementia, Limbic System, Semantic Dementia, Brain Damage, Medial Prefrontal Cortex, and Psychomotor Performance)