Network Representation of fMRI Data Using Visibility Graphs: The Impact of Motion and Test-Retest Reliability.

Visibility graphs provide a novel approach for analysing time-series data. Graph theoretical analysis of visibility graphs can provide new features for data mining applications in fMRI. However, visibility graphs features have not been used widely in the field of neuroscience. This is likely due to a lack of understanding of their robustness in the presence of noise (e.g., motion) and their test-retest reliability. In this study, we investigated visibility graph properties of fMRI data in the human connectome project (N = 1010) and tested their sensitivity to motion and test-retest reliability. We also characterised the strength of connectivity obtained using degree synchrony of visibility graphs. We found that strong correlation (r > 0.5) between visibility graph properties, such as the number of communities and average degrees, and motion in the fMRI data. The test-retest reliability (Intraclass correlation coefficient (ICC)) of graph theoretical features was high for the average degrees (0.74, 95% CI = [0.73, 0.75]), and moderate for clustering coefficient (0.43, 95% CI = [0.41, 0.44]) and average path length (0.41, 95% CI = [0.38, 0.44]). Functional connectivity between brain regions was measured by correlating the visibility graph degrees. However, the strength of correlation was found to be moderate to low (r < 0.35). These findings suggest that even small movement in fMRI data can strongly influence robustness and reliability of visibility graph features, thus, requiring robust motion correction strategies prior to data analysis. Further studies are necessary for better understanding of the potential application of visibility graph features in fMRI.

Prediction of cognitive outcome after mild traumatic brain injury from acute measures of communication within brain networks.

A considerable but ill-defined proportion of patients with mild traumatic brain injury (mTBI) experience persistent cognitive sequelae; the ability to identify such individuals early can help their neurorehabilitation. Here we tested the hypothesis that acute measures of efficient communication within brain networks are associated with patients' risk for unfavorable cognitive outcome six months after mTBI. Diffusion and T1-weighted magnetic resonance imaging, alongside cognitive measures, were obtained to map connectomes both one week and six months post injury in 113 adult patients with mTBI (71 males). For task-related brain networks, communication measures (characteristic path length, global efficiency, navigation efficiency) were moderately correlated with changes in cognition. Taking into account the covariance of age and sex, more unfavorable communication within networks were associated with worse outcomes within cognitive domains frequently impacted by mTBI (episodic and working memory, verbal fluency, inductive reasoning, and processing speed). Individuals with more unfavorable outcomes had significantly longer and less efficient pathways within networks supporting verbal fluency (all t > 2.786, p < .006), highlighting the vulnerability of language to mTBI. Participants in whom a task-related network was relatively inefficient one week post injury were up to eight times more likely to have unfavorable cognitive outcome pertaining to that task. Our findings suggest that communication measures within task-related networks identify mTBI patients who are unlikely to develop persistent cognitive deficits after mTBI. Our approach and findings can help to stratify mTBI patients according to their expected need for follow-up and/or neurorehabilitation.

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.

Characteristics of urban neighbourhood environments and cognitive age in mid-age and older adults.

In this cross-sectional study, we examined the extent to which features of the neighbourhood natural, built, and socio-economic environments were related to cognitive age in adults (N = 3418, Mage = 61 years) in Australia. Machine learning estimated an individual's cognitive age from assessments of processing speed, verbal memory, premorbid intelligence. A 'cognitive age gap' was calculated by subtracting chronological age from predicted cognitive age and was used as a marker of cognitive age. Greater parkland availability and higher neighbourhood socio-economic status were associated with a lower cognitive age gap score in confounder- and mediator-adjusted regression models. Cross-sectional design is a limitation. Living in affluent neighbourhoods with access to parks maybe beneficial for cognitive health, although selection mechanisms may contribute to the findings.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Exploring personalized structural connectomics for moderate to severe traumatic brain injury.

Graph theoretical analysis of the structural connectome has been employed successfully to characterize brain network alterations in patients with traumatic brain injury (TBI). However, heterogeneity in neuropathology is a well-known issue in the TBI population, such that group comparisons of patients against controls are confounded by within-group variability. Recently, novel single-subject profiling approaches have been developed to capture inter-patient heterogeneity. We present a personalized connectomics approach that examines structural brain alterations in five chronic patients with moderate to severe TBI who underwent anatomical and diffusion magnetic resonance imaging. We generated individualized profiles of lesion characteristics and network measures (including personalized graph metric GraphMe plots, and nodal and edge-based brain network alterations) and compared them against healthy reference cases (N = 12) to assess brain damage qualitatively and quantitatively at the individual level. Our findings revealed alterations of brain networks with high variability between patients. With validation and comparison to stratified, normative healthy control comparison cohorts, this approach could be used by clinicians to formulate a neuroscience-guided integrative rehabilitation program for TBI patients, and for designing personalized rehabilitation protocols based on their unique lesion load and connectome.

Structural-functional connectivity bandwidth predicts processing speed in mild traumatic brain Injury: A multiplex network analysis.

An emerging body of work has revealed alterations in structural (SC) and functional (FC) brain connectivity following mild TBI (mTBI), with mixed findings. However, these studies seldom integrate complimentary neuroimaging modalities within a unified framework. Multilayer network analysis is an emerging technique to uncover how white matter organization enables functional communication. Using our novel graph metric (SC-FC Bandwidth), we quantified the information capacity of synchronous brain regions in 53 mild TBI patients (46 females; age mean = 40.2 years (y), σ = 16.7 (y), range: 18-79 (y). Diffusion MRI and resting state fMRI were administered at the acute and chronic post-injury intervals. Moreover, participants completed a cognitive task to measure processing speed (30 Seconds and Counting Task; 30-SACT). Processing speed was significantly increased at the chronic, relative to the acute post-injury intervals (p = <0.001). Nonlinear principal components of direct (t = -1.84, p = 0.06) and indirect SC-FC Bandwidth (t = 3.86, p = <0.001) predicted processing speed with a moderate effect size (R2 = 0.43, p < 0.001), while controlling for age. A subnetwork of interhemispheric edges with increased SC-FC Bandwidth was identified at the chronic, relative to the acute mTBI post-injury interval (pFDR = 0.05). Increased interhemispheric SC-FC Bandwidth of this network corresponded with improved processing speed at the chronic post-injury interval (partial r = 0.32, p = 0.02). Our findings revealed that mild TBI results in complex reorganization of brain connectivity optimized for maximum information flow, supporting improved cognitive performance as a compensatory mechanism. Moving forward, this measurement may complement clinical assessment as an objective marker of mTBI recovery.

Increased cerebral activity during microsleeps reflects an unconscious drive to re-establish consciousness.

BACKGROUND: Microsleeps are brief instances of sleep, causing complete lapses in responsiveness and partial or total extended closure of both eyes. Microsleeps can have devastating consequences, particularly in the transportation sector. STUDY OBJECTIVES: Questions remain regarding the neural signature and underlying mechanisms of microsleeps. This study aimed to gain a better understanding of the physiological substrates of microsleeps, which might lead to a better understanding of the phenomenon. METHODS: Data from an earlier study, involving 20 healthy non-sleep-deprived subjects, were analysed. Each session lasted 50 min and required subjects to perform a 2-D continuous visuomotor tracking task. Simultaneous data collection included tracking performance, eye-video, EEG, and fMRI. A human expert visually inspected each participant's tracking performance and eye-video recordings to identify microsleeps. Our interest was in microsleeps of ≥4-s duration, leaving us with a total of 226 events from 10 subjects. The microsleep events were divided into four 2-s segments (pre, start, end, and post) (with a gap in the middle, between start and end segments, for microsleeps >4 s), then each segment was analysed relative to its prior segment by examining changes in source-reconstructed EEG power in the delta, theta, alpha, beta, and gamma bands. RESULTS: EEG power increased in the theta and alpha bands between the pre and start of microsleeps. There was also increased power in the delta, beta, and gamma bands between the start and end of microsleeps. Conversely, there was a reduction in power between the end and post of microsleeps in the delta and alpha bands. These findings support previous findings in the delta, theta, and alpha bands. However, increased power in the beta and gamma bands has not been previously reported. CONCLUSIONS: We contend that increased high-frequency activity during microsleeps reflects unconscious 'cognitive' activity aimed at re-establishing consciousness following falling asleep during an active task.

Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses.

Multiple myeloma (MM) is a cancer of malignant plasma cells in the bone marrow and extramedullary sites. We previously characterized a VQ model for human high-risk MM. The various VQ lines display different disease phenotypes and survival rates, suggesting significant intra-model variation. Here, we use whole-exome sequencing and copy number variation (CNV) analysis coupled with RNA-Seq to stratify the VQ lines into corresponding clusters: Group A cells had monosomy chromosome (chr) 5 and overexpressed genes and pathways associated with sensitivity to bortezomib (Btz) treatment in human MM patients. By contrast, Group B VQ cells carried recurrent amplification (Amp) of chr3 and displayed high-risk MM features, including downregulation of Fam46c, upregulation of cancer growth pathways associated with functional high-risk MM, and expression of Amp1q and high-risk UAMS-70 and EMC-92 gene signatures. Consistently, in sharp contrast to Group A VQ cells that showed short-term response to Btz, Group B VQ cells were de novo resistant to Btz in vivo. Our study highlights Group B VQ lines as highly representative of the human MM subset with ultrahigh risk.

Individualised profiling of white matter organisation in moderate-to-severe traumatic brain injury patients.

BACKGROUND AND PURPOSE: Approximately 65% of moderate-to-severe traumatic brain injury (m-sTBI) patients present with poor long-term behavioural outcomes, which can significantly impair activities of daily living. Numerous diffusion-weighted MRI studies have linked these poor outcomes to decreased white matter integrity of several commissural tracts, association fibres and projection fibres in the brain. However, most studies have focused on group-based analyses, which are unable to deal with the substantial between-patient heterogeneity in m-sTBI. As a result, there is increasing interest and need in conducting individualised neuroimaging analyses. MATERIALS AND METHODS: Here, we generated a detailed subject-specific characterisation of microstructural organisation of white matter tracts in 5 chronic patients with m-sTBI (29 - 49y, 2 females), presented as a proof-of-concept. We developed an imaging analysis framework using fixel-based analysis and TractLearn to determine whether the values of fibre density of white matter tracts at the individual patient level deviate from the healthy control group (n = 12, 8F, Mage = 35.7y, age range 25 - 64y). RESULTS: Our individualised analysis revealed unique white matter profiles, confirming the heterogenous nature of m-sTBI and the need of individualised profiles to properly characterise the extent of injury. Future studies incorporating clinical data, as well as utilising larger reference samples and examining the test-retest reliability of the fixel-wise metrics are warranted. CONCLUSIONS: Individualised profiles may assist clinicians in tracking recovery and planning personalised training programs for chronic m-sTBI patients, which is necessary to achieve optimal behavioural outcomes and improved quality of life.

Do neighbourhood traffic-related air pollution and socio-economic status moderate the associations of the neighbourhood physical environment with cognitive function? Findings from the AusDiab study.

Characteristics of the neighbourhood environment, including the built and natural environment, area-level socio-economic status (SES) and air pollution, have been linked to cognitive health. However, most studies have focused on single neighbourhood characteristics and have not considered the extent to which the effects of environmental factors may interact. We examined the associations of measures of the neighbourhood built and natural environment, area-level SES and traffic-related air pollution (TRAP) with two cognitive function domains (memory and processing speed), and the extent to which area-level SES and TRAP moderated the associations. We used cross-sectional data from the AusDiab3 study, an Australian cohort study of adults (mean age: 61 years) in 2011-12 (N = 4141) for which geocoded residential addresses were available. Spatial data were used to create composite indices of built environment complexity (population density, intersection density, non-commercial land use mix, commercial land use) and natural environment (parkland and blue spaces). Area-level SES was obtained from national census indices and TRAP was based on estimates of annual average levels of nitrogen dioxide (NO2). Confounder-adjusted generalised additive mixed models were used to estimate the independent associations of the environmental measures with cognitive function and the moderating effects of area-level SES and TRAP. The positive associations between built environment complexity and memory were stronger in those living in areas with higher SES and lower NO2 concentrations. A positive association between the natural environment and memory was found only in those living in areas with lower NO2 concentrations and average or below-average SES. Built environment complexity and the natural environment were positively related to processing speed. Complex urban environments and access to nature may benefit cognitive health in ageing populations. For higher-order cognitive abilities, such as memory, these positive effects may be stronger in areas with lower levels of TRAP.

Brain reward function in people who use cannabis: a systematic review.

Rationale: Cannabis is one of the most widely used psychoactive substances globally. Cannabis use can be associated with alterations of reward processing, including affective flattening, apathy, anhedonia, and lower sensitivity to natural rewards in conjunction with higher sensitivity to cannabis-related rewards. Such alterations have been posited to be driven by changes in underlying brain reward pathways, as per prominent neuroscientific theories of addiction. Functional neuroimaging (fMRI) studies have examined brain reward function in cannabis users via the monetary incentive delay (MID) fMRI task; however, this evidence is yet to be systematically synthesised. Objectives: We aimed to systematically integrate the evidence on brain reward function in cannabis users examined by the MID fMRI task; and in relation to metrics of cannabis exposure (e.g., dosage, frequency) and other behavioural variables. Method: We pre-registered the review in PROSPERO and reported it using PRISMA guidelines. Literature searches were conducted in PsycINFO, PubMed, Medline, CINAHL, and Scopus. Results: Nine studies were included, comprising 534 people with mean ages 16-to-28 years, of which 255 were people who use cannabis daily or almost daily, and 279 were controls. The fMRI literature to date led to largely non-significant group differences. A few studies reported group differences in the ventral striatum while participants anticipated rewards and losses; and in the caudate while participants received neutral outcomes. A few studies examined correlations between brain function and withdrawal, dosage, and age of onset; and reported inconsistent findings. Conclusions: There is emerging but inconsistent evidence of altered brain reward function in cannabis users examined with the MID fMRI task. Future fMRI studies are required to confirm if the brain reward system is altered in vulnerable cannabis users who experience a Cannabis Use Disorder, as postulated by prominent neuroscientific theories of addiction.

Structural-functional connectivity bandwidth of the human brain.

BACKGROUND: The human brain is a complex network that seamlessly manifests behaviour and cognition. This network comprises neurons that directly, or indirectly mediate communication between brain regions. Here, we show how multilayer/multiplex network analysis provides a suitable framework to uncover the throughput of structural connectivity (SC) to mediate information transfer-giving rise to functional connectivity (FC). METHOD: We implemented a novel method to reconcile SC and FC using diffusion and resting-state functional MRI connectivity data from 484 subjects (272 females, 212 males; age = 29.15 ± 3.47) from the Human Connectome Project. First, we counted the number of direct and indirect structural paths that mediate FC. FC nodes with indirect SC paths were then weighted according to their least restrictive SC path. We refer to this as SC-FC Bandwidth. We then mapped paths with the highest SC-FC Bandwidth across 7 canonical resting-state networks. FINDINGS: We found that most pairs of FC nodes were connected by SC paths of length two and three (SC paths of length >5 were virtually non-existent). Direct SC-FC connections accounted for only 10% of all SC-FC connections. The majority of FC nodes without a direct SC path were mediated by a proportion of two (44%) or three SC path lengths (39%). Only a small proportion of FC nodes were mediated by SC path lengths of four (5%). We found high-bandwidth direct SC-FC connections show dense intra- and sparse inter-network connectivity, with a bilateral, anteroposterior distribution. High bandwidth SC-FC triangles have a right superomedial distribution within the somatomotor network. High-bandwidth SC-FC quads have a superoposterior distribution within the default mode network. CONCLUSION: Our method allows the measurement of indirect SC-FC using undirected, weighted graphs derived from multimodal MRI data in order to map the location and throughput of SC to mediate FC. An extension of this work may be to explore how SC-FC Bandwidth changes over time, relates to cognition/behavior, and if this measure reflects a marker of neurological injury or psychiatric disorders.

Machine Learning for Prediction of Cognitive Health in Adults Using Sociodemographic, Neighbourhood Environmental, and Lifestyle Factors.

The environment we live in, and our lifestyle within this environment, can shape our cognitive health. We investigated whether sociodemographic, neighbourhood environment, and lifestyle variables can be used to predict cognitive health status in adults. Cross-sectional data from the AusDiab3 study, an Australian cohort study of adults (34-97 years) (n = 4141) was used. Cognitive function was measured using processing speed and memory tests, which were categorized into distinct classes using latent profile analysis. Sociodemographic variables, measures of the built and natural environment estimated using geographic information system data, and physical activity and sedentary behaviours were used as predictors. Machine learning was performed using gradient boosting machine, support vector machine, artificial neural network, and linear models. Sociodemographic variables predicted processing speed (r2 = 0.43) and memory (r2 = 0.20) with good accuracy. Lifestyle factors also accurately predicted processing speed (r2 = 0.29) but weakly predicted memory (r2 = 0.10). Neighbourhood and built environment factors were weak predictors of cognitive function. Sociodemographic (AUC = 0.84) and lifestyle (AUC = 0.78) factors also accurately classified cognitive classes. Sociodemographic and lifestyle variables can predict cognitive function in adults. Machine learning tools are useful for population-level assessment of cognitive health status via readily available and easy-to-collect data.

Network diffusion model predicts neurodegeneration in limb-onset Amyotrophic Lateral Sclerosis.

OBJECTIVE: Emerging evidences suggest that the trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS. METHODS: We measured degeneration in limb-onset ALS patients (n = 14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n = 12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. In order to investigate whether network spread on the brain connectome derived from healthy individuals were significant findings, we compared our findings against network spread simulated on random networks. RESULTS: The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Network spread simulated on the random networks showed that the findings using healthy brain connectomes are significantly different from null models. INTERPRETATION: Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.

Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia.

Tyrosine kinase inhibitors (TKIs) have revolutionised the management of chronic myeloid leukaemia (CML), with the disease now having a five-year survival rate over 80%. The primary focus in the treatment of CML has been on improving the specificity and potency of TKIs to inhibit the activation of the BCR::ABL1 kinase and/or overcoming resistance driven by mutations in the BCR::ABL1 oncogene. However, this approach may be limited in a significant proportion of patients who develop TKI resistance despite the effective inhibition of BCR::ABL1. These patients may require novel therapeutic strategies that target both BCR::ABL1-dependent and BCR::ABL1-independent mechanisms of resistance. The combination treatment strategies that target alternative survival signalling, which may contribute towards BCR::ABL1-independent resistance, could be a successful strategy for eradicating residual leukaemic cells and consequently increasing the response rate in CML patients.

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.

A Gut Instinct on Leukaemia: A New Mechanistic Hypothesis for Microbiota-Immune Crosstalk in Disease Progression and Relapse.

Despite significant advances in the treatment of Chronic Myeloid and Acute Lymphoblastic Leukaemia (CML and ALL, respectively), disease progression and relapse remain a major problem. Growing evidence indicates the loss of immune surveillance of residual leukaemic cells as one of the main contributors to disease recurrence and relapse. More recently, there was an appreciation for how the host's gut microbiota predisposes to relapse given its potent immunomodulatory capacity. This is especially compelling in haematological malignancies where changes in the gut microbiota have been identified after treatment, persisting in some patients for years after the completion of treatment. In this hypothesis-generating review, we discuss the interaction between the gut microbiota and treatment responses, and its capacity to influence the risk of relapse in both CML and ALL We hypothesize that the gut microbiota contributes to the creation of an immunosuppressive microenvironment, which promotes tumour progression and relapse.

Longitudinal mapping of cortical surface changes in Huntington's Disease.

This paper investigated cortical folding in Huntington's disease to understand how disease progression impacts the surface of the cortex. Cortical morphometry changes in eight gyral based regions of interest (i.e. the left and right hemispheres of the lateral occipital, precentral, superior frontal and rostral middle gyri) were examined. We used existing neuroimaging data from IMAGE-HD, comprising 26 pre-symptomatic, 26 symptomatic and 24 healthy control individuals at three separate time points (baseline, 18-month, 30-month). Local gyrification index and cortical thickness were derived as the measures of cortical morphometry using FreeSurfer 6.0's longitudinal pipeline. The gyral based regions of interest were identified using the Desikan-Killiany Atlas. A Group by Time repeated measures ANCOVA was conducted for each region of interest. We found significantly lower LGI at a group level in the right hemisphere lateral occipital region and both hemispheres of the precentral region; as well as significantly reduced cortical thickness at a group level in both hemispheres of the lateral occipital and precentral regions and the right hemisphere of the superior frontal region. We also found a Group by Time interaction for Local gyrification index in the right hemisphere lateral occipital region. This change was largely driven by a significant decrease in the symptomatic group between baseline and 18-months. Additionally, lower local gyrification index and cortical thickness were associated with higher disease burden score. These findings demonstrate that significant longitudinal decline in right hemisphere local gyrification index is evident during manifest disease in lateral occipital cortex and that these changes are more profound in individuals with greater disease burden score.