IMAGE-HD Study Research Articles

The shape of things to come. Mapping spatiotemporal progression of striatal morphology in Huntington disease: The IMAGE-HD study

Mapping the spatiotemporal progression of neuroanatomical change in Huntington's Disease (HD) is fundamental to the development of bio-measures for prognostication. Statistical shape analysis to measure the striatum has been performed in HD, however there have been a limited number of longitudinal studies. To address these limitations, we utilised the Spherical Harmonic Point Distribution Method (SPHARM-PDM) to generate point distribution models of the striatum in individuals, and used linear mixed models to test for localised shape change over time in pre-manifest HD (pre-HD), symp-HD (symp-HD) and control individuals. Longitudinal MRI scans from the IMAGE-HD study were used (baseline, 18 and 30 months). We found significant differences in the shape of the striatum between groups. Significant group-by-time interaction was observed for the putamen bilaterally, but not for caudate. A differential rate of shape change between groups over time was observed, with more significant deflation in the symp-HD group in comparison with the pre-HD and control groups. CAG repeats were correlated with bilateral striatal shape in pre-HD and symp-HD. Robust statistical analysis of the correlates of striatal shape change in HD has confirmed the suitability of striatal morphology as a potential biomarker correlated with CAG-repeat length, and potentially, an endophenotype.

Hippocampal morphology in Huntington's disease, implications for plasticity and pathogenesis: The IMAGE-HD study

While striatal changes in Huntington's Disease (HD) are well established, few studies have investigated changes in the hippocampus, a key neuronal hub. Using MRI scans obtained from the IMAGE-HD study, hippocampi were manually traced and then analysed with the Spherical Harmonic Point Distribution Method (SPHARM-PDM) in 36 individuals with presymptomatic-HD, 37 with early symptomatic-HD, and 36 healthy matched controls. There were no significant differences in overall hippocampal volume between groups. Interestingly we found decreased bilateral hippocampal volume in people with symptomatic-HD who took selective serotonin reuptake inhibitors compared to those who did not, despite no significant differences in anxiety, depressive symptoms, or motor incapacity between the two groups. In symptomatic-HD, there was also significant shape deflation in the right hippocampal head, showing the utility of using manual tracing and SPHARM-PDM to characterise subtle shape changes which may be missed by other methods. This study confirms previous findings of the lack of hippocampal volumetric differentiation in presymptomatic-HD and symptomatic-HD compared to controls. We also find novel shape and volume findings in those with symptomatic-HD, especially in relation to decreased hippocampal volume in those treated with SSRIs.

Selective perforant-pathway atrophy in Huntington disease: MRI analysis of hippocampal subfields.

While individuals with Huntington disease (HD) show memory impairment that indicates hippocampal dysfunction, the available literature does not consistently identify structural evidence for involvement of the whole hippocampus but rather suggests that hippocampal atrophy may be confined to certain hippocampal subregions. We processed T1-weighted MRI from IMAGE-HD study using FreeSurfer 7.0 and compared the volumes of the hippocampal subfields among 36 early motor symptomatic (symp-HD), 40 pre-symptomatic (pre-HD), and 36 healthy control individuals across three timepoints over 36 months. Mixed-model analyses revealed significantly lower subfield volumes in symp-HD, compared with pre-HD and control groups, in the subicular regions of the perforant-pathway: presubiculum, subiculum, dentate gyrus, tail, and right molecular layer. These adjoining subfields aggregated into a single principal component, which demonstrated an accelerated rate of atrophy in the symp-HD. Volumes between pre-HD and controls did not show any significant difference. In the combined HD groups, CAG repeat length and disease burden score were associated with presubiculum, molecular layer, tail, and perforant-pathway subfield volumes. Hippocampal left tail and perforant-pathway subfields were associated with motor onset in the pre-HD group. Hippocampal subfields atrophy in early symptomatic HD affects key regions of the perforant-pathway, which may implicate the distinctive memory impairment at this stage of illness. Their volumetric associations with genetic and clinical markers suggest the selective susceptibility of these subfields to mutant Huntingtin and disease progression.

Investigating longitudinal changes to frontal cortico-striatal tracts in Huntington’s disease: the IMAGE-HD study

The striatum is the principal site of disease pathology in Huntington’s disease and contains neural connections to numerous cortical brain regions. Studies examining abnormalities to neural connections find that white matter integrity is compromised in HD; however, further regional, and longitudinal investigation is required. This paper is the first longitudinal investigation into region-based white-matter integrity changes in Huntington’s Disease. The aim of this study was to better understand how disease progression impacts white matter tracts connecting the striatum to the prefrontal and motor cortical regions in HD. We used existing neuroimaging data from IMAGE-HD, comprised of 25 pre-symptomatic, 27 symptomatic, and 25 healthy controls at three separate time points (baseline, 18-months, 30-months). Fractional anisotropy, axial diffusivity and radial diffusivity were derived as measures of white matter microstructure. The anatomical regions of interest were identified using the Desikan-Killiany brain atlas. A Group by Time repeated measures ANCOVA was conducted for each tract of interest and for each measure. We found significantly lower fractional anisotropy and significantly higher radial diffusivity in the symptomatic group, compared to both the pre-symptomatic group and controls (the latter two groups did not differ from each other), in the rostral middle frontal and superior frontal tracts; as well as significantly higher axial diffusivity in the rostral middle tracts only. We did not find a Group by Time interaction for any of the white matter integrity measures. These findings demonstrate that whilst the microstructure of white matter tracts, extending from the striatum to these regions of interest, are compromised during the symptomatic stages of Huntington’s disease, 36-month follow-up did not show progressive changes in these measures. Additionally, no correlations were found between clinical measures and tractography changes, indicating further investigations into the relationship between tractography changes and clinical symptoms in Huntington’s disease are required.

Early white matter pathology in the fornix of the limbic system in Huntington disease

Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The typical motor symptoms have been associated with basal ganglia pathology. However, psychiatric and cognitive symptoms often precede the motor component and may be due to changes in the limbic system. Recent work has indicated pathology in the hypothalamus in HD but other parts of the limbic system have not been extensively studied. Emerging evidence suggests that changes in HD also include white matter pathology. Here we investigated if the main white matter tract of the limbic system, the fornix, is affected in HD. We demonstrate that the fornix is 34% smaller already in prodromal HD and 41% smaller in manifest HD compared to controls using volumetric analyses of MRI of the IMAGE-HD study. In post-mortem fornix tissue from HD cases, we confirm the smaller fornix volume in HD which is accompanied by signs of myelin breakdown and reduced levels of the transcription factor myelin regulating factor but detect no loss of oligodendrocytes. Further analyses using RNA-sequencing demonstrate downregulation of oligodendrocyte identity markers in the fornix of HD cases. Analysis of differentially expressed genes based on transcription-factor/target-gene interactions also revealed enrichment for binding sites of SUZ12 and EZH2, components of the Polycomb Repressive Complex 2, as well as RE1 Regulation Transcription Factor. Taken together, our data show that there is early white matter pathology of the fornix in the limbic system in HD likely due to a combination of reduction in oligodendrocyte genes and myelin break down.

Morphometric in vivo evidence of thalamic atrophy correlated with cognitive and motor dysfunction in Huntington's disease: The IMAGE-HD study

In Huntington's disease (HD), neurodegeneration causes progressive atrophy to the striatum, cortical areas, and white matter tracts - components of corticostriatal circuitry. Such processes may affect the thalamus, a key circuit node. We investigated whether differences in dorsal thalamic morphology were detectable in HD, and whether thalamic atrophy was associated with neurocognitive, neuropsychiatric and motor dysfunction.Magnetic resonance imaging scans and clinical outcome measures were obtained from 34 presymptomatic HD (pre-HD), 29 early symptomatic HD (symp-HD), and 26 healthy control individuals who participated in the IMAGE-HD study. Manual region of interest (ROI) segmentation was conducted to measure dorsal thalamic volume, and thalamic ROI underwent shape analysis using the spherical harmonic point distribution method.The symp-HD group had significant thalamic volumetric reduction and global shape deflation, indicative of atrophy, compared to pre-HD and control groups. Thalamic atrophy significantly predicted neurocognitive and motor dysfunction within the symp-HD group only.Thalamic morphology differentiates symp-HD from pre-HD and healthy individuals. Thalamic changes may be one of the structural bases (endomorphotypes), of the endophenotypic neurocognitive and motor manifestations of disease. Future research should continue to investigate the thalamus as a potential in vivo biomarker of disease progression in HD.

Striatal morphology and neurocognitive dysfunction in Huntington disease: The IMAGE-HD study

We aimed to investigate the relationship between striatal morphology in Huntington disease (HD) and measures of motor and cognitive dysfunction. MRI scans, from the IMAGE-HD study, were obtained from 36 individuals with pre-symptomatic HD (pre-HD), 37 with early symptomatic HD (symp-HD), and 36 healthy matched controls. The neostriatum was manually segmented and a surface-based parametric mapping protocol derived two pointwise shape measures: thickness and surface dilation ratio. Significant shape differences were detected between all groups. Negative associations were detected between lower thickness and surface area shape measure and CAG repeats, disease burden score, and UHDRS total motor score. In symp-HD, UPSIT scores were correlated with higher thickness in left caudate tail and surface dilation ratio in left posterior putamen; Stroop scores were positively correlated with the thickness of left putamen head and body. Self-paced tapping (slow) was correlated with higher thickness and surface dilation ratio in the right caudate in symp-HD and with bilateral putamen in pre-HD. Self-paced tapping (fast) was correlated with higher surface dilation ratio in the right anterior putamen in symp-HD. Shape changes correlated with functional measures subserved by corticostriatal circuits, suggesting that the neostriatum is a potentially useful structural basis for characterisation of endophenotypes of HD.

Altered Cortical Morphometry in Pre-manifest Huntington's Disease: Cross-sectional Data from the IMAGE-HD Study.

Huntington's disease (HD) is an inherited progressive neurodegenerative disease mainly associated with subcortical striatal atrophy. There is also strong evidence showing cerebral atrophy and cortical thinning; however, limited research has investigated altered patterns of cortical folding in this disease. Here, we investigated cortical morphometry via both gyrification index (GI, a measure of cortical folding) and cortical thinning. The localized GI was examined using a novel GI, namely LB-GI. As part of a cross-sectional study, pre-manifest (pre-HD) individuals (n = 29) and matched controls (n = 29) underwent T1-MRI using data from the IMAGE-HD study. Compared to controls, pre-HD individuals demonstrated significantly lower GI in the left superior parietal and the right superior temporal regions and greater cortical thinning in the bilateral pre-central and the superior frontal gyri and left caudal middle frontal gyrus, as well as the superior parietal region. For the first time, we report evidence of abnormal localized cortical folding in pre-HD. We also provide evidence that cortical folding impacts different regions of the cortical surface more so than cortical thickness. As a result, we propose a potential new biological marker that may increase our understanding of the neuropathology of HD. Greater understanding of brain changes could inform new therapeutic approaches and target points for clinical trials.

Reduced amygdala volumes are related to motor and cognitive signs in Huntington's disease: The IMAGE-HD study.

In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than the striatum has been recently gaining attention. The amygdala is one such area, which has been investigated in only eight structural magnetic resonance imaging studies to date, but with inconsistent findings. This is the largest MRI study to date examining manually traced amygdala volumes in HD participants and the relationship of amygdala volumes to clinical measures of HD. Our study included 35 healthy control participants, and groups of 35 pre-symptomatic, and 36 symptomatic HD participants. When comparing the pre-symptomatic and symptomatic HD groups together against the control group, amygdala volumes were significantly lower in HD than controls and in symptomatic HD than pre-symptomatic HD. When examining relationships between amygdala volumes and clinical measures of HD, significantly smaller amygdala volumes were associated with worse motor and cognitive signs. For pre-symptomatic HD participants who were close to disease onset, smaller amygdala volumes were also associated with higher levels of anxiety symptoms. These findings suggest that the amygdala is affected in pre-symptomatic and symptomatic HD, and that the amygdala is related to the clinical profile of HD before onset of motor symptoms.

Functional Brain Correlates of Neuropsychiatric Symptoms in Presymptomatic Huntington's Disease: The IMAGE-HD Study.

Neuropsychiatric disturbances are common in Huntington's Disease (HD) and have been observed in gene-positive individuals several years prior to the onset of motor symptoms. The neural mechanism underpinning the development of neuropsychiatric problems in HD remain unclear. To investigate whether neural activity during working memory is associated with neuropsychiatric symptoms in premanifest Huntington's Disease. functional magnetic resonance imaging (fMRI) data from Pre-HD far from onset (pre-HDfar, n = 18), pre-HD close to onset (pre-HDclose, n = 17), and controls (n = 32) were analysed. Correlations were performed between fMRI activity in three regions of interest [bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] and neuropsychiatric scores. In the pre-HDclose group, increased symptoms of obsessive compulsion and depression were associated with decreased blood-oxygen-level-dependent (BOLD) fMRI activity in the right DLPFC and ACC during 1-BACK and 2-BACK working memory conditions. In the pre-HDfar group increased symptoms of depression was associated with decreased right DLPFC BOLD fMRI activity during 2-BACK working memory only. The findings suggest that association between neuropsychiatric function and fMRI activity is more readily detectable at higher working memory loads, and becomes more pronounced in those closer to onset.

Iron accumulation in the basal ganglia in Huntington's disease: cross-sectional data from the IMAGE-HD study

ObjectivesTo measure iron accumulation in the basal ganglia in Huntington's disease (HD) using quantitative susceptibility mapping (QSM), and to ascertain its relevance in terms of clinical and disease severity.MethodsIn this...

Functional brain correlates of psychiatric function in Huntington's disease: The Image-HD study

Functional brain correlates of psychiatric function in Huntington's disease: The Image-HD study

Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study

ObjectiveTo quantify 18-month changes in white matter microstructure in premanifest (pre-HD) and symptomatic Huntington's disease (symp-HD). To investigate baseline clinical, cognitive and motor symptoms that are predictive of white matter microstructural change over 18months. MethodDiffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18months. Unbiased tract-based spatial statistics (TBSS) methods were used to identify longitudinal changes in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) of white matter. Stepwise linear regression models were used to identify baseline clinical, cognitive, and motor measures that are predictive of longitudinal diffusion changes. ResultsSymp-HD compared to controls showed 18-month reductions in FA in the corpus callosum and cingulum white matter. Symp-HD compared to pre-HD showed increased RD in the corpus callosum and striatal projection pathways. FA in the body, genu, and splenium of the corpus callosum was significantly associated with a baseline clinical motor measure (Unified Huntington's Disease Rating Scale: total motor scores: UHDRS–TMS) across both HD groups. This measure was also the only independent predictor of longitudinal decline in FA in all parts of the corpus callosum across both HD groups. ConclusionsWe provide direct evidence of longitudinal decline in white matter microstructure in symp-HD. Although pre-HD did not show longitudinal change, clinical symptoms and motor function predicted white matter microstructural changes for all gene positive subjects. These findings suggest that loss of axonal integrity is an early hallmark of neurodegenerative changes which are clinically relevant.

E23 Functional Brain Correlates Of Psychiatric Function In Presymptomatic Huntington's Disease: The Image-hd Study

<h3>Background</h3> Changes in prefrontal brain responses as well as psychiatric deficits are detected in Huntington’s disease (HD) prior to diagnosis. <h3>Aims</h3> This study investigated the relationship between psychiatric symptoms and functional brain activity during working memory performance in individuals with pre-symptomatic hd (pre-hd) using the image-hd data set. <h3>Methods/techniques</h3> Pre-HD far from onset (pre-hd far, n = 17), pre-hd close to onset (pre-hd close, n = 18), and control (n = 32) groups completed an n-back task (0, 1 and 2-back) during functional magnetic resonance imaging (fMRI). Brain regions of interest included the bilateral dorsolateral prefrontal cortex (dlpfc) and anterior cingulate cortex (acc). Correlations were performed between blood-oxygen-level-dependent (bold) activity in each brain region and scores on a battery of neuropsychiatric inventories, while controlling for age, gender, and accuracy on the n-back task. <h3>Results/outcome</h3> For both 1- and 2-back conditions, significant negative correlations were found in the pre-hd close group between neuropsychiatric disturbance and bold activation in both the right dlpfc and acc. During 2-back, a significant negative correlation was found in the pre-hd far group between depression symptoms and right dlpfc bold. For 1-back, no significant correlations were found in the pre-hd far group. <h3>Conclusions</h3> These findings suggest that as pre-hd individuals approach onset, increased psychiatric disturbance is associated with decreased functional brain activity, which becomes more wide-spread during higher working memory loads.

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions. We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons. Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group. We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization. Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease.

Functional changes during working memory in Huntington’s disease: 30-month longitudinal data from the IMAGE-HD study

We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2-BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD.

Multi-Modal Neuroimaging in Premanifest and Early Huntington’s Disease: 18 Month Longitudinal Data from the IMAGE-HD Study

IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington’s disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (<15 years) and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.

Functional and connectivity changes during working memory in Huntington’s disease: 18 month longitudinal data from the IMAGE-HD study

BackgroundThis study aimed to characterize, for the first time, 18month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington’s disease (pre-HD) and symptomatic HD (symp-HD). MethodsFunctional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18months follow-up. ResultsCompared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18months only in the pre-HD group. ConclusionsLongitudinal reductions in connectivity over 18months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.

Significant longitudinal change in neostriatal volume in premanifest and manifest Huntington's disease: The IMAGE-HD study

Significant longitudinal change in neostriatal volume in premanifest and manifest Huntington's disease: The IMAGE-HD study

Longitudinal tracking of white matter connectivity in Huntington's disease: 30 month longitudinal data from the IMAGE-HD study

Event Abstract Back to Event Longitudinal tracking of white matter connectivity in Huntington's disease: 30 month longitudinal data from the IMAGE-HD study Govinda Poudel1*, Juan Dominguez1, Louisa Salmon1, Andrew Churchyard2, Phyllis Chua1, Julie Stout1, Gary F. Egan1 and Nellie Georgiou-Karistianis1 1 Monash University, School of Psychology and Psychiatry, Australia 2 Monash Medical Centre, Australia Background: Disruption of structural integrity of specific neural circuits has been proposed to be one of the possible mechanisms underlying progressive deterioration in cognitive and motor function in Huntington’s disease (HD). The aim of this study was to use an unbiased longitudinal diffusion tensor imaging (DTI) analysis approach to track the microstructural integrity of white matter connections in pre-manifest (pre-HD) and symptomatic HD (symp-HD) individuals. Methods: DTI data from 22 pre-HD, 19 symp-HD, and 22 healthy controls was collected at baseline, 18 months, and 30 months, from a cohort of participants in the IMAGE-HD study. DTI data were preprocessed to remove eddy-current and motion artefacts. For longitudinal analysis, we adopted a tensor-based registration pipeline that used full tensor information in DTI data to drive improved alignment over multiple time points and across groups. White matter tracts of interest were delineated by segmenting fractional anisotropy (FA) map of the group atlas using a locally adaptive segmentation algorithm. Body, genu, and splenium of corpus callosum fibre bundle were located by normalization in an atlas space. Microstructural integrity was assessed by statistical analysis of FA values. Results: We observed selective loss in integrity of corpus callosum fibre bundle in both pre-HD close to onset and symp-HD groups. Symp-HD showed significant reduction of FA in all parts of corpus callosum, whereas in pre-HD close to onset FA reduction was topographically selective and localized in the splenium and body of corpus callosum. Discussion: Given that the corpus callosum plays an important role in interhemispheric connectivity, our findings suggest for the first time, that there is a progressive disruption in cortico-cortical structural connectivity in HD. Keywords: Diffusion Tensor Imaging, Huntington's disease, Corpus Callosum, fractional anisotropy, connectivity Conference: ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013. Presentation Type: Poster Topic: Motor Citation: Poudel G, Dominguez J, Salmon L, Churchyard A, Chua P, Stout J, Egan GF and Georgiou-Karistianis N (2013). Longitudinal tracking of white matter connectivity in Huntington's disease: 30 month longitudinal data from the IMAGE-HD study. Conference Abstract: ACNS-2013 Australasian Cognitive Neuroscience Society Conference. doi: 10.3389/conf.fnhum.2013.212.00012 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Oct 2013; Published Online: 25 Nov 2013. * Correspondence: Dr. Govinda Poudel, Monash University, School of Psychology and Psychiatry, Clayton, Australia, govinda.poudel@monash.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Govinda Poudel Juan Dominguez Louisa Salmon Andrew Churchyard Phyllis Chua Julie Stout Gary F Egan Nellie Georgiou-Karistianis Google Govinda Poudel Juan Dominguez Louisa Salmon Andrew Churchyard Phyllis Chua Julie Stout Gary F Egan Nellie Georgiou-Karistianis Google Scholar Govinda Poudel Juan Dominguez Louisa Salmon Andrew Churchyard Phyllis Chua Julie Stout Gary F Egan Nellie Georgiou-Karistianis PubMed Govinda Poudel Juan Dominguez Louisa Salmon Andrew Churchyard Phyllis Chua Julie Stout Gary F Egan Nellie Georgiou-Karistianis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.