ORCID Profile
0000-0003-4685-1380
Current Organisations
Monash University
,
University of Melbourne
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Atomic molecular and optical physics | Nanofabrication growth and self assembly | Astronomical instrumentation | Photonics optoelectronics and optical communications | Nonlinear optics and spectroscopy
Publisher: SAGE Publications
Date: 25-03-2019
Abstract: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is h ering progress in development of treatments. To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor ( p 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.
Publisher: SAGE Publications
Date: 06-03-2023
DOI: 10.1177/13524585231157206
Abstract: We investigated choroid plexus (CP) volume in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established relapsing–remitting multiple sclerosis (RRMS) and healthy controls (HCs). Three-dimensional (3D) T1, T2-FLAIR and diffusion-weighted sequences were acquired from 44 ON CIS patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 HCs were also included for comparison. CP volumes was larger in both ON CIS and RRMS groups compared to HCs, but not significantly different between ON CIS and RRMS patients (analysis of covariance (ANCOVA) adjusted for multiple comparisons). Twenty-three ON CIS patients who converted to clinically definite MS (MS) demonstrated CP volume similar to RRMS patients, but significantly larger compared to HCs. In this sub-group, CP volume was not associated with the severity of optic nerve inflammation or long-term axonal loss, not with brain lesion load. A transient increase of CP volume was observed following an occurrence of new MS lesions on brain magnetic resonance imaging (MRI). Enlarged CP can be observed very early in a disease. It transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.
Publisher: SAGE Publications
Date: 21-05-2022
DOI: 10.1177/13524585221094464
Abstract: Gait in people with multiple sclerosis (PwMS) is affected even when no changes can be observed on clinical examination. A sensitive measure of gait deterioration is stability however, its correlation with motor tract damage has not yet been established. To compare stability between PwMS and healthy controls (HCs) and determine associations between stability and diffusion magnetic resonance image (MRI) measures of axonal damage in selected sensorimotor tracts. Twenty-five PwMS (Expanded Disability Status Scale (EDSS) 2.5) and 15 HCs walked on a treadmill. Stability from sacrum (LDE SAC ), shoulder (LDE SHO ) and cervical (LDE CER ) was calculated using the local ergence exponent (LDE). Participants underwent a 7T-MRI brain scan to obtain fibre-specific measures of axonal loss within the corticospinal tract (CST), interhemispheric sensorimotor tract (IHST) and cerebellothalamic tract (CTT). Correlation analyses between LDE and fibre density (FD) within tracts, fibre cross-section (FC) and FD modulated by FC (FDC) were conducted. Between-groups LDE differences were analysed using analysis of variance (ANOVA). Correlations between all stability measures with CST FD , between CST FDC with LDE SAC and LDE CER , and LDE CER with IHST FD and IHST FDC were significant yet moderate ( R −0.4). Stability was significantly different between groups. Poorer gait stability is associated with corticospinal tract (CST) axonal loss in PwMS with no-to-low disability and is a sensitive indicator of neurodegeneration.
Publisher: SAGE Publications
Date: 26-10-2020
Abstract: Network abnormalities could help explain physical disability in multiple sclerosis (MS), which remains poorly understood. This study investigates functional network efficiency changes in the sensorimotor system. We included 222 MS patients, ided into low disability (LD, Expanded Disability Status Scale (EDSS) ⩽3.5, n = 185) and high disability (HD, EDSS ⩾6, n = 37), and 82 healthy controls (HC). Functional connectivity was assessed between 23 sensorimotor regions. Measures of efficiency were computed and compared between groups using general linear models corrected for age and sex. Binary logistic regression models related disability status to local functional network efficiency (LE), brain volumes and demographics. Functional connectivity patterns of regions important for disability were explored. HD patients demonstrated significantly higher LE of the left primary somatosensory cortex (S1) and right pallidum compared to LD and HC, and left premotor cortex compared to HC only. The logistic regression model for disability ( R 2 = 0.38) included age, deep grey matter volume and left S1 LE. S1 functional connectivity was increased with prefrontal and secondary sensory areas in HD patients, compared to LD and HC. Clinical disability in MS associates with functional sensorimotor increases in efficiency and connectivity, centred around S1, independent of structural damage.
Publisher: SAGE Publications
Date: 30-09-2022
DOI: 10.1177/13524585221125372
Abstract: Upper and lower limb disabilities are hypothesized to have partially independent underlying (network) disturbances in multiple sclerosis (MS). This study investigated functional network predictors and longitudinal network changes related to upper and lower limb progression in MS. Two-hundred fourteen MS patients and 58 controls underwent functional magnetic resonance imaging (fMRI), dexterity (9-Hole Peg Test) and mobility (Timed 25-Foot Walk) measurements (baseline and 5 years). Patients were stratified into progressors ( % decline) or non-progressors. Functional network efficiency was calculated using static (over entire scan) and dynamic (fluctuations during scan) approaches. Baseline measurements were used to predict progression significant predictors were explored over time. In both limbs, progression was related to supplementary motor area and caudate efficiency (dynamic and static, respectively). Upper limb progression showed additional specific predictors cortical grey matter volume, putamen static efficiency and posterior associative sensory (PAS) cortex, putamen, primary somatosensory cortex and thalamus dynamic efficiency. Additional lower limb predictors included motor network grey matter volume, caudate (dynamic) and PAS (static). Only the caudate showed a decline in efficiency over time in one group (non-progressors). Disability progression can be predicted using sensorimotor network measures. Upper and lower limb progression showed unique predictors, possibly indicating different network disturbances underlying these types of progression in MS.
Publisher: Wiley
Date: 03-01-2022
DOI: 10.1111/CNS.13786
Abstract: To investigate the factors influencing enlarged perivascular space (EPVS) characteristics at the onset of acute ischemic stroke (AIS), and whether the PVS characteristics can predict later post‐stroke epilepsy (PSE). A total of 312 patients with AIS were identified, of whom 58/312 (18.6%) developed PSE. Twenty healthy participants were included as the control group. The number of PVS in the basal ganglia (BG), centrum semiovale (CS), and midbrain (MB) was manually calculated on T 2 ‐weighted MRI. The scores and asymmetry index (AI) of EPVS in each region were compared among the enrolled participants. Other potential risk factors for PSE were also analyzed, including NIHSS at admission and stroke etiologies. The EPVS scores were significantly higher in the bilateral BG and CS of AIS patients compared to those of the control group (both p 0.01). No statistical differences in EPVS scores in BG, CS, and MB were obtained between the PSE group and the nonepilepsy AIS group (all p 0.01). However, markedly different AI scores in CS were found between the PSE group and the nonepilepsy AIS group ( p = 0.004). Multivariable analysis showed that high asymmetry index of EPVS (AI≥0.2) in CS was an independent predictor for PSE (OR = 3.7, 95% confidence interval 1.5–9.1, p = 0.004). Asymmetric distribution of EPVS in CS may be an independent risk factor and a novel imaging biomarker for the development of PSE. Further studies to understand the mechanisms of this association and confirmation with larger patient populations are warranted.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2015
DOI: 10.1038/NRNEUROL.2015.174
Abstract: The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS). Such an approach may ultimately provide objective and reproducible measures of cognitive dysfunction that offer an innovative capability to refine diagnosis, improve prognostication, and more accurately codify disease burden. A further idend may be the validation and application of biomarkers that can be used in studies aimed at identifying and monitoring preventative, protective and even restorative properties of novel neurotherapeutics in MS. This Review discusses the utility of ocular motor measures in patients with MS to characterize disruption to wide-ranging networks that support cognitive function.
Publisher: Springer Science and Business Media LLC
Date: 13-12-2016
DOI: 10.1038/TP.2016.250
Abstract: DNA methylation of the Fragile X mental retardation 1 ( FMR1 ) exon 1/intron 1 boundary has been associated with executive dysfunction in female carriers of a FMR1 premutation (PM: 55–199 CGG repeats), whereas neuroanatomical changes have been associated with executive dysfunction in PM males. To our knowledge, this study for the first time examined the inter-relationships between executive function, neuroanatomical structure and molecular measures (DNA methylation and FMR1 mRNA levels in blood) in PM and control ( CGG repeats) females. In the PM group, FMR1 intron 1 methylation was positively associated with executive function and cortical thickness in middle and superior frontal gyri, and left inferior parietal gyrus. By contrast, in the control group, FMR1 intron 1 methylation was negatively associated with cortical thickness of the left middle frontal gyrus and superior frontal gyri. No significant associations were revealed for either group between FMR1 mRNA and neuroanatomical structure or executive function. In the PM group, the lack of any significant association between FMR1 mRNA levels and phenotypic measures found in this study suggests that either FMR1 expression is not well conserved between tissues, or that FMR1 intron 1 methylation is linked to neuroanatomical and cognitive phenotype in PM females via a different mechanism.
Publisher: BMJ
Date: 12-2021
DOI: 10.1136/BMJOPEN-2021-055019
Abstract: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder for which there are currently no disease-modifying therapies. The neuropathology of PSP is associated with the accumulation of hyperphosphorylated tau in the brain. We have previously shown that protein phosphatase 2 activity in the brain is upregulated by sodium selenate, which enhances dephosphorylation. Therefore, the objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying therapy for PSP. This will be a multi-site, phase 2b, double-blind, placebo-controlled trial of sodium selenate. 70 patients will be recruited at six Australian academic hospitals and research institutes. Following the confirmation of eligibility at screening, participants will be randomised (1:1) to receive 52 weeks of active treatment (sodium selenate 15 mg three times a day) or matching placebo. Regular safety and efficacy visits will be completed throughout the study period. The primary study outcome is change in an MRI volume composite (frontal lobe+midbrain–3rd ventricle) over the treatment period. Analysis will be with a general linear model (GLM) with the MRI composite at 52 weeks as the dependent variable, treatment group as an independent variable and baseline MRI composite as a covariate. Secondary outcomes are change in PSP rating scale, clinical global impression of change (clinician) and change in midbrain mean diffusivity. These outcomes will also be analysed with a GLM as above, with the corresponding baseline measure entered as a covariate. Secondary safety and tolerability outcomes are frequency of serious adverse events, frequency of down-titration occurrences and frequency of study discontinuation. Additional, as yet unplanned, exploratory outcomes will include analyses of other imaging, cognitive and biospecimen measures. The study was approved by the Alfred Health Ethics Committee (594/20). Each participant or their legally authorised representative and their study partner will provide written informed consent at trial commencement. The results of the study will be presented at national and international conferences and published in peer-reviewed journals. Australian New Zealand Clinical Trials Registry (ACTRN12620001254987).
Publisher: Springer International Publishing
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 10-10-2019
DOI: 10.1038/S41598-019-51267-W
Abstract: A single mild traumatic brain injury (mTBI) typically causes only transient symptoms, but repeated mTBI (RmTBI) is associated with cumulative and chronic neurological abnormalities. Clinical management of mTBI is challenging due to the heterogeneous, subjective and transient nature of symptoms, and thus would be aided by objective biomarkers. Promising biomarkers including advanced magnetic resonance imaging (MRI) and plasma levels of select proteins were examined here in a rat model of RmTBI. Rats received either two mild fluid percussion or sham injuries administered five days apart. Rats underwent MRI and behavioral testing 1, 3, 5, 7, and 30 days after the second injury and blood s les were collected on days 1, 7, and 30. Structural and diffusion-weighted MRI revealed that RmTBI rats had abnormalities in the cortex and corpus callosum. Proteomic analysis of plasma found that RmTBI rats had abnormalities in markers indicating axonal and vascular injury, metabolic and mitochondrial dysfunction, and glial reactivity. These changes occurred in the presence of ongoing cognitive and sensorimotor deficits in the RmTBI rats. Our findings demonstrate that RmTBI can result in chronic neurological abnormalities, provide insight into potential contributing pathophysiological mechanisms, and supports the use of MRI and plasma protein measures as RmTBI biomarkers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-05-2016
Publisher: IEEE
Date: 2005
Publisher: Oxford University Press (OUP)
Date: 23-06-2022
DOI: 10.1093/BRAINCOMMS/FCAC164
Abstract: Visual snow syndrome is a neurological condition characterized by continuous visual disturbance and a range of non-visual symptoms, including tinnitus and migraine. Little is known about the pathological mechanisms underlying visual snow syndrome. Here, we assessed brain morphometry and microstructure in visual snow syndrome patients using high-resolution structural and quantitative MRI. Forty visual snow syndrome patients (22 with migraine) and 43 controls underwent 7-Tesla MRI (MP2RAGE, 0.75 mm isotropic resolution). Volumetric and quantitative T1 values were extracted for white and grey matter regions and compared between groups. Where regions were significantly different between groups (false discovery rate corrected for multiple comparisons), post hoc comparisons were examined between patients with and without migraine. For visual snow syndrome patients, significant MRI variables were correlated with clinical severity (number of visual symptoms, perceived visual snow intensity, disruptiveness, fatigue and quality of life) and psychiatric symptoms prevalent in visual snow syndrome (depression, anxiety and depersonalization). Finally, cortical regions and in idual thalamic nuclei were studied. Compared with controls, visual snow syndrome patients demonstrated a trend towards larger brain and white matter volumes and significantly lower T1 values for the entire cortex (P & 0.001), thalamus (P = 0.001) and pallidum (P = 0.001). For the patient group, thalamic T1 correlated with number of visual symptoms (P = 0.019, r = 0.390) and perceived disruptiveness of visual snow (P = 0.010, r = 0.424). These correlations did not survive multiple comparison corrections. As for specificity in visual snow syndrome group, T1 changes were most evident in caudal regions (occipital cortices) followed by parietal, temporal and prefrontal cortices. T1 values differed between groups for most in idual thalamic nuclei. No differences were revealed between patients with and without migraine. In visual snow syndrome patients, we observed no changes in morphometry, instead widespread changes in grey matter microstructure, which followed a caudal-rostral pattern and affected the occipital cortices most profoundly. Migraine did not appear to independently affect these changes. Lower T1 values may potentially result from higher neurite density, myelination or increased iron levels in the visual snow syndrome brain. Further investigation of these changes may enhance our understanding of the pathogenesis of visual snow syndrome, ultimately leading to new treatment strategies.
Publisher: Elsevier BV
Date: 05-2020
Publisher: SAGE Publications
Date: 07-2019
Publisher: Oxford University Press (OUP)
Date: 16-03-2021
DOI: 10.1093/BRAINCOMMS/FCAB032
Abstract: Multiple sclerosis is a neuroinflammatory disease of the CNS that is associated with significant irreversible neuro-axonal loss, leading to permanent disability. There is thus an urgent need for in vivo markers of axonal loss for use in patient monitoring or as end-points for trials of neuroprotective agents. Advanced diffusion MRI can provide markers of diffuse loss of axonal fibre density or atrophy within specific white matter pathways. These markers can be interrogated in specific white matter tracts that underpin important functional domains such as sensorimotor function. This study aimed to evaluate advanced diffusion MRI markers of axonal loss within the major sensorimotor tracts of the brain, and to correlate the degree of axonal loss in these tracts to precise kinematic measures of hand and foot motor control and gait in minimally disabled people with multiple sclerosis. Twenty-eight patients (Expanded Disability Status Scale & 4, and Kurtzke Functional System Scores for pyramidal and cerebellar function ≤ 2) and 18 healthy subjects underwent ultra-high field 7 Tesla diffusion MRI for calculation of fibre-specific measures of axonal loss (fibre density, reflecting diffuse axonal loss and fibre cross-section reflecting tract atrophy) within three tracts: cortico-spinal tract, interhemispheric sensorimotor tract and cerebello-thalamic tracts. A visually guided force-matching task involving either the hand or foot was used to assess visuomotor control, and three-dimensional marker-based video tracking was used to assess gait. Fibre-specific axonal markers for each tract were compared between groups and correlated with visuomotor task performance (force error and lag) and gait parameters (stance, stride length, step width, single and double support) in patients. Patients displayed significant regional loss of fibre cross-section with minimal loss of fibre density in all tracts of interest compared to healthy subjects (family-wise error corrected p-value & 0.05), despite relatively few focal lesions within these tracts. In patients, reduced axonal fibre density and cross-section within the corticospinal tracts and interhemispheric sensorimotor tracts were associated with larger force tracking error and gait impairments (shorter stance, smaller step width and longer double support) (family-wise error corrected p-value & 0.05). In conclusion, significant gait and motor control impairments can be detected in minimally disabled people with multiple sclerosis that correlated with axonal loss in major sensorimotor pathways of the brain. Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.
Publisher: American Society of Neuroradiology (ASNR)
Date: 02-2022
DOI: 10.3174/AJNR.A7398
Publisher: Frontiers Media SA
Date: 08-09-2022
DOI: 10.3389/FNEUR.2022.945034
Abstract: Predicting long-term visual outcomes and axonal loss following acute optic neuritis (ON) is critical for choosing treatment. Predictive models including all clinical and paraclinical measures of optic nerve dysfunction following ON are lacking. Using a prospective study method, to identify 1 and 3 months predictors of 6 and 12 months visual outcome (low contrast letter acuity 2.5%) and axonal loss [retinal nerve fiber layer thickness and multifocal evoked potential (mfVEP) litude] following acute ON. In total, 37 patients of acute ON onset were evaluated within 14 days using between-eye asymmetry of visual acuity, color vision (Ishihara plates), optical coherence tomography, mfVEP, and optic nerve magnetic resonance imaging [magnetic transfer ratio (MTR) and diffusion tensor imaging (DTI)]. Visual outcome at 6 and 12 months was best predicted by Ishihara asymmetry at 1 and 3 months following ON onset. Axonal loss at 6 and 12 months was reliably predicted by Ishihara asymmetry at 1 month. Optic nerve MTR and DTI at 3 months post-acute ON could predict axonal loss at 6 and 12 months. Simple Ishihara asymmetry testing 1 month after acute ON onset can best predict visual outcome and axonal loss at 6 and 12 months in a clinical or research setting.
Publisher: Cold Spring Harbor Laboratory
Date: 23-08-2022
DOI: 10.1101/2022.08.23.22279105
Abstract: People with Multiple Sclerosis (MS) have a larger choroid plexus (CP) volume than healthy controls. We investigated CP volume in early MS by quantitatively assessing brain MRI scans in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established Relapsing Remitting Multiple Sclerosis (RRMS) and healthy controls. Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion-weighted images were acquired from 44 CIS ON patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 healthy controls were also included for comparison. ANOVA revealed significantly larger CP volumes in both ON CIS and RRMS groups compared to healthy controls (p .001 for both), but no difference between ON CIS and RRMS patients (p=0.9) Twenty-three ON CIS patients who converted to CDMS during 10 years of follow-up demonstrated CP volume similar to RRMS patients, but significantly larger compared to healthy controls (p .001). Increased CP volume was identified even in a sub-group of patients without MS-like lesions at baseline (p .001). A significant (∼6%) transient increase of CP volume was observed following a new bout of inflammation, which, however, returned to pre-inflammatory state few months later. CP volume was not associated with the severity of acute inflammation of the optic nerve or long-term optic nerve axonal loss, not with brain lesion load or severity of tissue damage within lesions. Our data demonstrate that enlarged CP can be observe very early in a disease, transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.NEUROIMAGE.2014.02.023
Abstract: Heavy demands are placed on the brain's attentional capacity when selecting a target item in a cluttered visual scene, or when reading. It is widely accepted that such attentional selection is mediated by top-down signals from higher cortical areas to early visual areas such as the primary visual cortex (V1). Further, it has also been reported that there is considerable variation in the surface area of V1. This variation may impact on either the number or specificity of attentional feedback signals and, thereby, the efficiency of attentional mechanisms. In this study, we investigated whether in idual differences between humans performing attention-demanding tasks can be related to the functional area of V1. We found that those with a larger representation in V1 of the central 12° of the visual field as measured using BOLD signals from fMRI were able to perform a serial search task at a faster rate. In line with recent suggestions of the vital role of visuo-spatial attention in reading, the speed of reading showed a strong positive correlation with the speed of visual search, although it showed little correlation with the size of V1. The results support the idea that the functional size of the primary visual cortex is an important determinant of the efficiency of selective spatial attention for simple tasks, and that the attentional processing required for complex tasks like reading are to a large extent determined by other brain areas and inter-areal connections.
Publisher: Wiley
Date: 19-05-2021
DOI: 10.1002/ACN3.51320
Abstract: Artificial intelligence (AI)‐based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human‐led validated consensus quality control criteria (OSCAR‐IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI‐based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five‐point expansion of the OSCAR‐IB criteria to embrace AI (OSCAR‐AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.MSARD.2022.103495
Abstract: Upper limb tremor is common in people with multiple sclerosis (pwMS) and can affect day to day function, impacting on their tremor related quality of life (tremor-QOL). The Quality of Life in Essential Tremor Questionnaire (QUEST) is a tremor-QOL scale, however it has not been validated for use in pwMS. This is in contrast to the Multiple Sclerosis Impact Scale (MSIS-29), a MS health related QOL (MS-QOL) scale validated in pwMS. The aim of this study was to quantify tremor-QOL in pwMS using both the QUEST and MSIS-29 and establish the convergent validity of the QUEST scale with the MSIS-29. Data were derived from an existing registered clinical trial studying the efficacy of Botox (onabotulinumtoxinA) compared to placebo in pwMS-related upper limb tremor (ACTRN12617000379314). We determined MS-related disability (Expanded Disability status scale score (EDSS)), tremor severity (Bain and Findley Clinical Tremor Rating Scale (Bain)), cerebellar function (Scale for the Assessment and rating of Ataxia (SARA)), and upper limb manual dexterity (9 Hole Peg Test (9-HPT)). The QUEST and MSIS-29 were used to quantify tremor-QOL and MS-QOL respectively. Convergent validity was investigated by examining the correlation between QUEST and MSIS-29, and the pattern of correlation of the two scales compared to the EDSS, SARA, BAIN and 9-HPT. Our cohort of 57 patients (16 male 41 female), mean age of 47.6, had moderate MS-related disability with median EDSS score of 5 (IQR = 3.5). Median Bain score was 8, indicating mild tremor severity, which corresponded to mild to moderately poor tremor-QOL given mean Quest Summary Index (QSI) of 45.7. QSI correlated to tremor severity as measured by Bain total score (rs(55) = 0.339, p < 0.01), manual dexterity as measured by 9-HPT (rs(55) = 0.304, p < 0.05), and MS disease activity measured by EDSS (rs(55) = 0.347, p < 0.01). MSIS-29 also showed correlations to EDSS, and 9-HPT, but did not correlate to Bain total score. There was a strong relationship between QSI and MSIS-29 in pwMS (r(55) = 0.709, p < 0.01). In this cross-sectional study, we found that both the MS-QOL and tremor-QOL of pwMS with upper limb tremor was reduced. We were also the first to demonstrate that tremor-QOL in pwMS with upper limb tremor can be measured using the QUEST, which may be better suited for use in pwMS affected by arm-tremor than the MSIS-29. There is a lack of literature to specifically address tremor-QOL in pwMS, and more research is warranted.
Publisher: Wiley
Date: 10-09-2020
DOI: 10.1002/MRM.27993
Abstract: The clinical application of sodium MRI is h ered due to relatively low image quality and associated long acquisition times. Compressed sensing (CS) aims at a reduction of measurement time, but has been found to encompass quantitative estimation bias when used in low SNR x-Nuclei imaging. This work analyses CS in quantitative human brain sodium MRI from unders led acquisitions and provides recommendations for tissue sodium concentration (TSC) estimation. CS reconstructions from 3D radial acquisitions of 5 healthy volunteers were investigated over varying unders ling factors (USFs) and CS penalty weights on different sparsity domains, Wavelet, Discrete Cosine Transform (DCT), and Identity. Resulting images were compared with highly s led and unders led NUFFT-based images and evaluated for image quality (i.e. structural similarity), image intensity bias, and its effect on TSC estimates in gray and white matter. Wavelet-based CS reconstructions show highest image quality with stable TSC estimates for most USFs. Up to an USF of 4, images showed good structural detail. DCT and Identity-based CS enable good image quality, however show a bias in TSC with a reduction in estimates across USFs. The image intensity bias is lowest in Wavelet-based reconstructions and enables an up to fourfold acquisition speed up while maintaining good structural detail. The associated acquisition time reduction can facilitate a translation of sodium MRI into clinical routine.
Publisher: Wiley
Date: 13-09-2012
DOI: 10.1002/HBM.21343
Publisher: Cold Spring Harbor Laboratory
Date: 15-08-2020
DOI: 10.1101/2020.08.13.20174664
Abstract: Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually-guided force-matching of hand or foot in 28 minimally disabled pwMS and 17 healthy controls (HC) using ultra-high field 7-Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p =0.002) and more erroneous (+0.15 N, p =0.001) lower limb tracking, together with higher primary motor and premotor cortex activation, and lower cerebellar activation compared to HC. No differences were seen in upper limb performance or activation. Functional activation levels of cerebellar, visual and motor areas correlated with task performance. These results demonstrate that ultra-high field fMRI during complex hand and foot tracking can identify subtle impairments in movement and brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2020
DOI: 10.1101/2020.01.14.903559
Abstract: Endpoint-to-endpoint fibre bundle connectivity estimated using spherical deconvolution & streamlines tractography in diffusion MRI may be excessive in the presence of pathologies that involve truncation of axons within the white matter. Here we propose a simple modification to an existing method that directly quantifies and corrects for this over-estimation.
Publisher: Wiley
Date: 05-03-2021
DOI: 10.1002/HBM.25389
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2020
DOI: 10.1101/2020.05.15.094938
Abstract: Cerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are h ered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS. Examine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMS We recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle. Loss of cerebellar FDC was associated with increased SARA (r=-0.42, p .01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p .01) and tremor severity (rho=0.41, p=0.01). Fibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression.
Publisher: MDPI AG
Date: 24-11-2022
DOI: 10.3390/BIOMEDICINES10123026
Abstract: The prodromal phase of Parkinson’s disease (PD) is characterised by many non-motor symptoms, and these have recently been posited to be predictive of later diagnosis. Genetic rodent models can develop non-motor phenotypes, providing tools to identify mechanisms underlying the early development of PD. However, it is not yet clear how reproducible non-motor phenotypes are amongst genetic PD rodent models, whether phenotypes are age-dependent, and the translatability of these phenotypes has yet to be explored. A systematic literature search was conducted on studies using genetic PD rodent models to investigate non-motor phenotypes cognition, anxiety/depressive-like behaviour, gastrointestinal (GI) function, olfaction, circadian rhythm, cardiovascular and urinary function. In total, 51 genetic models of PD across 150 studies were identified. We found outcomes of most phenotypes were inconclusive due to inadequate studies, assessment at different ages, or variation in experimental and environmental factors. GI dysfunction was the most reproducible phenotype across all genetic rodent models. The mouse model harbouring mutant A53T, and the wild-type hα-syn overexpression (OE) model recapitulated the majority of phenotypes, albeit did not reliably produce concurrent motor deficits and nigral cell loss. Furthermore, animal models displayed different phenotypic profiles, reflecting the distinct genetic risk factors and heterogeneity of disease mechanisms. Currently, the inconsistent phenotypes within rodent models pose a challenge in the translatability and usefulness for further biomechanistic investigations. This review highlights opportunities to improve phenotype reproducibility with an emphasis on phenotypic assay choice and robust experimental design.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.NEUROIMAGE.2008.12.047
Abstract: Recently, there has been strong interest in the development of imaging techniques to quantify axonal and myelin pathology in patients with multiple sclerosis (MS). Optic neuritis, a condition characterised by inflammatory demyelination of the optic nerve, is one of the commonest sites of MS relapse, and exhibits similar pathological alterations to MS lesions elsewhere in the central nervous system (CNS). Unlike other regions of the CNS, however, the function of the optic nerve can be accurately assessed using clinical measures, as well as electrophysiological techniques such as visual evoked potential recordings. Therefore, optic neuritis is useful for investigating the relationship between abnormalities in optic nerve structure, assessed using magnetic resonance imaging (MRI), and visual dysfunction, assessed clinically and electrophysiologically. The aims of the present study were to assess optic nerve structural abnormalities in patients with a history of unilateral optic neuritis using MRI, and then to identify correlations between abnormalities in optic nerve MRI and visual dysfunction. Ten controls and sixteen patients underwent high resolution optic nerve diffusion tensor imaging (DTI), T2- and T1-weighted MRI. In addition, Snellen visual acuity and the latency and litude of multifocal visual evoked potentials (mfVEP) were tested in all patients. Diffusion and volumetric MRI indices were correlated to mfVEP functional indices. Significant abnormalities were detected in MRI and mfVEP measures in patients' affected nerves compared to unaffected optic nerves or optic nerves from healthy controls. Reduced mfVEP litude in the affected side significantly correlated with both affected optic nerve atrophy (R=0.58, p=0.02) and reduced fractional anisotropy (FA) (R=0.52, p=0.04). However, atrophy and reduced FA did not correlate with each other. To further investigate this disassociation, we used linear regression analysis with optic nerve atrophy and optic nerve FA as independent variables and mfVEP litude as the dependent variable. The resulting linear regression model was highly significant (R=0.819, p=0.001). These results show that, 4 years after unilateral optic neuritis, MRI-based measures of optic nerve structural abnormalities (decreased anisotropy and volume) independently predict visual dysfunction.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-05-2017
DOI: 10.1212/WNL.0000000000003979
Abstract: To examine the interrelationships between fragile X mental retardation 1 ( FMR1 ) mRNA and the FMR1 exon 1/intron 1 boundary methylation, white matter microstructure, and executive function, in women with a FMR1 premutation expansion (PM 55–199 CGG repeats) and controls (CGG 44). Twenty women with PM without fragile X-associated tremor/ataxia syndrome (FXTAS) and 20 control women between 22 and 54 years of age completed this study. FMR1 mRNA and methylation levels for 9 CpG sites within the FMR1 exon 1/intron 1 boundary from peripheral blood s les were analyzed. To measure white matter microstructure, diffusion-weighted imaging was used, from which fractional anisotropy (FA) and mean diffusivity (MD) values from anatomic regions within the corpus callosum and cerebellar peduncles were extracted. Executive function was assessed across a range of tasks. No differences were revealed in white matter microstructure between women with PM and controls. However, we reveal that for women with PM (but not controls), higher FMR1 mRNA correlated with lower MD values within the middle cerebellar peduncle and Paced Auditory Serial Addition Test scores, higher methylation of the FMR1 exon 1/intron 1 boundary correlated with lower MD within the inferior and middle cerebellar peduncles and longer prosaccade latencies, and higher FA values within the corpus callosum and cerebellar peduncle regions corresponded to superior executive function. We provide evidence linking white matter microstructure to executive dysfunction and elevated FMR1 mRNA and FMR1 exon 1/intron 1 boundary methylation in women with PM without FXTAS. This suggests that the FXTAS phenotype may not be distinct but may form part of a spectrum of PM involvement.
Publisher: Public Library of Science (PLoS)
Date: 28-05-2015
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-02-2021
DOI: 10.1167/TVST.10.2.8
Publisher: Frontiers Media SA
Date: 02-02-2018
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.AUTREV.2018.06.010
Abstract: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression. Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis. Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/2764538
Abstract: Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential litude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51% p = 0.006 ). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450 , p = 0.006 RD: R = - 0.428 , p = 0.009 MD: R = - 0.365 , p = 0.029 ). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months ( R = 0.489 , p = 0.039 ). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.
Publisher: Wiley
Date: 25-09-2019
DOI: 10.1002/MRM.27484
Abstract: Fast bi‐exponential transverse signal decay compounds sodium image quality. This work aims at enhancing image characteristics using a special case of r ed hybrid encoding (RHE). Zero‐gradient‐excitation (zG RF )‐RHE provides (1) gradient‐free excitation for high flip angle, artifact‐free excitation profiles and (2) gradient r ing during dead‐time for the optimization of encoding time (t enc ) to reduce T 2 * signal decay influence during acquisition. Radial zG RF ‐RHE and standard radial UTE were investigated over a range of receiver bandwidths in simulations, phantom and in vivo brain experiments. Central k‐space in zG RF ‐RHE was acquired through single point measurements at the minimum achievable TE. T 2 * blurring artifacts and image SNR and CNR were assessed. zG RF ‐RHE enabled 90° flip angle artifact‐free excitation, whereas gradient pre‐r ing provided greater t enc efficiency for any readout bandwidths. Experiments confirmed simulation results, revealing sharper edge characteristics particularly at short readout durations (T RO ). Significant SNR improvements of up to 4.8% were observed for longer T RO . zG RF ‐RHE allows for artifact‐free high flip angle excitation with time‐efficient encoding improving on image characteristics. This hybrid encoding concept with gradient pre‐r ing is trajectory independent and can be introduced in any center‐out UTE trajectory design.
Publisher: Wiley
Date: 14-10-2016
DOI: 10.1002/HBM.23438
Publisher: IEEE
Date: 08-2008
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 05-2021
Publisher: SAGE Publications
Date: 26-05-2015
Abstract: The pathophysiology of multiple sclerosis (MS) tremor is uncertain with limited phenotypical studies available. To investigate whether dystonia contributes to MS tremor and its severity. MS patients ( n = 54) with and without disabling uni- or bilateral upper limb tremor were recruited (39 limbs per group). We rated tremor severity, writing and Archimedes spiral drawing cerebellar dysfunction (SARA score) the Global Dystonia Scale (GDS) for proximal and distal upper limbs, dystonic posturing, mirror movements, geste antagoniste, and writer’s cr . Geste antagoniste, mirror dystonia, and dystonic posturing were more frequent and severe ( p 0.001) and dystonia scores were correlated with tremor severity in tremor compared to non-tremor patients. A 1-unit increase in distal dystonia predicted a 0.52-Bain unit (95% confidence interval (CI) 0.08–0.97), p = 0.022) increase in tremor severity and a 1-unit (95% CI 0.48–1.6, p = 0.001) increase in drawing scores. A 1-unit increase in proximal dystonia predicted 0.93-Bain unit increase (95% CI 0.45–1.41, p 0.001) in tremor severity and 1.5-units (95% CI 0.62–2.41, p = 0.002) increase in the drawing score. Cerebellar function in the tremor limb and tremor severity was correlated ( p 0.001). Upper limb dystonia is common in MS tremor suggesting that MS tremor pathophysiology involves cerebello-pallido-thalamo-cortical network dysfunction.
Publisher: Elsevier BV
Date: 2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 21-02-2012
DOI: 10.1167/IOVS.11-8864
Abstract: To compare white matter (WM) injuries associated with vision loss in multiple sclerosis (MS) and optic neuritis (ON). Twenty-three patients with clinically definite relapsing-remitting MS and chronic unilateral ON and 14 neurologically healthy volunteers were monocularly tested with Sloan 100%, 2.5%, and 1.25% contrast visual acuity charts. Primary visual pathway and whole-brain WM injury were assessed with optical coherence tomography (OCT) and diffusion tensor imaging (DTI). OCT and DTI correlates of high- and low-contrast visual impairment were identified using correlation analyses. The MS patients displayed significantly reduced retinal nerve fiber layer (RNFL) thickness and altered optic nerve and radiation DTI measures compared with the controls. In the patients, 2.5% and 1.25% contrast letter acuity in the unaffected eye correlated significantly and independently with optic nerve and optic radiation DTI measures. Visual acuity in affected eyes did not correlate with optic nerve or optic radiation DTI measures, but did correlate with DTI measures in prefrontal and temporal brain regions that were shown to connect structurally to visual cortices. In unaffected eyes, visual impairment was associated with WM injury in the visual pathway. In contrast, irrecoverable visual impairment after ON was associated with injury to frontal WM, which potentially impairs the capacity for remapping visual processing.
Publisher: Wiley
Date: 16-01-2019
DOI: 10.1002/MRM.27659
Abstract: Parameter mapping in sodium MRI data is challenging due to inherently low SNR and spatial resolution, prompting the need to employ robust models and estimation techniques. This work aims to develop a continuum model of sodium A closed-form continuum model was derived assuming a gamma distribution of The continuum model demonstrated comparable estimation performance to the bi-exponential model. The parameter maps provided improved contrast between tissue structures. The fast component fraction, an indicator of the heterogeneity of localised sodium motion regimes in tissue, was zero in CSF and high in WM structures. The continuum distribution model provides high quality, high contrast parameter maps, and informative voxelwise estimates of the relative weighting between fast and slow decay components.
Publisher: Public Library of Science (PLoS)
Date: 26-12-2013
Publisher: Wiley
Date: 03-09-2014
DOI: 10.1002/HBM.22329
Publisher: Frontiers Media SA
Date: 02-06-2020
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
DOI: 10.1007/S10334-018-0690-Z
Abstract: Ultra-high-field functional MRI (UHF-fMRI) allows for higher spatiotemporal resolution imaging. However, higher-resolution imaging entails coverage limitations. Processing partial-coverage images using standard pipelines leads to sub-optimal results. We aimed to develop a simple, semi-automated pipeline for processing partial-coverage UHF-fMRI data using widely used image processing algorithms. We developed automated pipelines for optimized skull stripping and co-registration of partial-coverage UHF functional images, using built-in functions of the Centre for Functional Magnetic Resonance Imaging of the Brain's (FMRIB's) Software library (FSL) and advanced normalization tools. We incorporated the pipelines into the FSL's functional analysis pipeline and provide a semi-automated optimized partial-coverage functional analysis pipeline (OPFAP). Compared to the standard pipeline, the OPFAP yielded images with 15 and 30% greater volume of non-zero voxels after skull stripping the functional and anatomical images, respectively (all p = 0.0004), which reflected the conservation of cortical voxels lost when the standard pipeline was used. The OPFAP yielded the greatest Dice and Jaccard coefficients (87 and 80%, respectively all p < 0.0001) between the co-registered participant gyri maps and the template gyri maps, demonstrating the goodness of the co-registration results. Furthermore, the greatest volume of group-level activation in the most number of functionally relevant regions was observed when the OPFAP was used. Importantly, group-level activations were not observed when using the standard pipeline. These results suggest that the OPFAP should be used for processing partial-coverage UHF-fMRI data for detecting high-resolution macroscopic blood oxygenation level-dependent activations.
Publisher: ACM
Date: 29-01-2018
Publisher: Oxford University Press (OUP)
Date: 04-07-2022
DOI: 10.1093/BRAINCOMMS/FCAC185
Abstract: Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long–Evans rats (n = 14) compared with sham animals (n = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats (P & 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration.
Publisher: Oxford University Press (OUP)
Date: 03-2022
DOI: 10.1093/BRAINCOMMS/FCAC065
Abstract: Axonal loss in the CNS is a key driver of progressive neurological impairments in people with multiple sclerosis. Currently, there are no established methods for tracking axonal loss clinically. This study aimed to determine the sensitivity of longitudinal diffusion MRI-derived fibre-specific measures of axonal loss in people with multiple sclerosis. Fibre measures were derived from diffusion MRI acquired as part of a standard radiological MRI protocol and were compared (i) to establish measures of neuro-axonal degeneration: brain parenchymal fraction and retinal nerve fibre layer thickness and (ii) between different disease stages: clinically isolated syndrome and early/late relapsing–remitting multiple sclerosis. Retrospectively identified data from 59 people with multiple sclerosis (18 clinically isolated syndrome, 22 early and 19 late relapsing–remitting) who underwent diffusion MRI as part of their routine clinical monitoring were collated and analysed. Twenty-six patients had 1-year and 14 patients had a 2-year follow-up. Brain parenchymal fraction was calculated from 3D MRI scans, and fibre-specific measures were calculated from diffusion MRI using multi-tissue constrained spherical deconvolution. At each study visit, patients underwent optical coherence tomography to determine retinal nerve fibre layer thickness, and standard neurological assessment expanded the disability status scale. We found a significant annual fibre-specific neuro-axonal degeneration (mean ± SD = −3.49 ± 3.32%, P & 0.001) that was ∼7 times larger than the annual change of brain parenchymal fraction (−0.53 ± 0.95%, P & 0.001), and more than four times larger than annual retinal nerve fibre layer thinning (−0.75 ± 2.50% P = 0.036). Only fibre-specific measures showed a significant difference in annual degeneration between the disease stages (P = 0.029). Reduced brain parenchymal fraction, retinal nerve fibre layer thickness and fibre-specific measures were moderately related to higher expanded disability status scale (rho = −0.368, rho = −0.408 and rho = −0.365, respectively). Fibre-specific measures can be measured from data collected within a standard radiological multiple sclerosis study and are substantially more sensitive to longitudinal change compared with brain atrophy and retinal nerve fibre layer thinning.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/8361290
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male N L 3 R 451 C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in N L 3 R 451 C mice. N L 3 R 451 C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in N L 3 R 451 C mice. This study is the first to show altered mating behavior in the N L 3 R 451 C mouse and has provided new insights into the aggressive phenotype in this model.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Public Library of Science (PLoS)
Date: 17-07-2019
Publisher: Wiley
Date: 08-12-2022
DOI: 10.1002/HBM.26176
Abstract: Visual snow syndrome (VSS) is a neurological disorder characterized by a range of continuous visual disturbances. Little is known about the functional pathological mechanisms underlying VSS and their effect on brain network topology, studied using high‐resolution resting‐state (RS) 7 T MRI. Forty VSS patients and 60 healthy controls underwent RS MRI. Functional connectivity matrices were calculated, and global efficiency (network integration), modularity (network segregation), local efficiency (LE, connectedness neighbors) and eigenvector centrality (significance node in network) were derived using a dynamic approach (temporal fluctuations during acquisition). Network measures were compared between groups, with regions of significant difference correlated with known aberrant ocular motor VSS metrics (shortened latencies and higher number of inhibitory errors) in VSS patients. Lastly, nodal co‐modularity, a binary measure of node pairs belonging to the same module, was studied. VSS patients had lower modularity, supramarginal centrality and LE dynamics of multiple (sub)cortical regions, centered around occipital and parietal lobules. In VSS patients, lateral occipital cortex LE dynamics correlated positively with shortened prosaccade latencies ( p = .041, r = .353). In VSS patients, occipital, parietal, and motor nodes belonged more often to the same module and demonstrated lower nodal co‐modularity with temporal and frontal regions. This study revealed reduced dynamic variation in modularity and local efficiency strength in the VSS brain, suggesting that brain network dynamics are less variable in terms of segregation and local clustering. Further investigation of these changes could inform our understanding of the pathogenesis of the disorder and potentially lead to treatment strategies.
Publisher: Springer Science and Business Media LLC
Date: 27-06-2022
DOI: 10.1007/S12311-022-01435-Y
Abstract: Multiple sclerosis (MS) is a progressive disease that often affects the cerebellum. It is characterised by demyelination, inflammation, and neurodegeneration within the central nervous system. Damage to the cerebellum in MS is associated with increased disability and decreased quality of life. Symptoms include gait and balance problems, motor speech disorder, upper limb dysfunction, and oculomotor difficulties. Monitoring symptoms is crucial for effective management of MS. A combination of clinical, neuroimaging, and task-based measures is generally used to diagnose and monitor MS. This paper reviews the present and new tools used by clinicians and researchers to assess cerebellar impairment in people with MS (pwMS). It also describes recent advances in digital and home-based monitoring for people with MS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-10-2011
Publisher: Wiley
Date: 10-09-2020
DOI: 10.1002/MRM.27975
Abstract: To demonstrate simultaneous T A single-echo (SE) MP2RAGE sequence at 7 tesla was extended to ME with 4 bipolar gradient echo readouts. T The ME combined T High-resolution structural T
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-07-2021
DOI: 10.1212/WNL.0000000000012125
Abstract: To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations. To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms “quantitative” and “optical coherence tomography” from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes. A total of 116 authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans, and suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants' consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%. The modified Delphi method resulted in an expert-led guideline (evidence Class III Grading of Recommendations, Assessment, Development and Evaluations [GRADE] criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition analysis, nomenclature and abbreviations, and statistical approach. It will be essential to update these recommendations to new research and practices regularly.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.JOCN.2012.03.022
Abstract: The initiating events in multiple sclerosis (MS) plaque formation are poorly understood. Retrospective analysis of serial imaging data can improve the understanding of tissue changes characterising acute MS lesion evolution. This study aimed to assess lesion evolution using diffusion tensor imaging data from serially acquired scans from 22 patients with MS. Mean diffusivity (MD) and fractional anisotropy (FA) were measured from 13 suitable plaques from five patients and carefully matched regions of contralateral normal-appearing white matter. Measurement times were on average: 5 months and 1 month prior to, during, and 1 month and 2 months post gadolinium-enhancement. A significant increase in MD (7.25%) but no change in FA was observed in white matter areas that exhibited enhancement 5 months later. The pre-lesional MD increase was significantly correlated with the MD increase 2 months subsequent to enhancement (R=0.73, p=0.04) but not to the MD increase during enhancement (R=0.11). These results suggest that MD is sensitive to tissue changes that precede blood-brain barrier (BBB) breakdown by at least 5 months and that MD assessments may predict injury following BBB restoration.
Publisher: Oxford University Press (OUP)
Date: 19-06-2021
Abstract: Sports-related concussion (SRC) is a form of mild traumatic brain injury that has been linked to long-term neurological abnormalities. Australian rules football is a collision sport with wide national participation and is growing in popularity worldwide. However, the chronic neurological consequences of SRC in Australian footballers remain poorly understood. This study investigated the presence of brain abnormalities in Australian footballers with a history of sports-related concussion (HoC) using multimodal MRI. Male Australian footballers with HoC (n = 26), as well as noncollision sport athletes with no HoC (n = 27), were recruited to the study. None of the footballers had sustained a concussion in the preceding 6 months, and all players were asymptomatic. Data were acquired using a 3T MRI scanner. White matter integrity was assessed using diffusion tensor imaging. Cortical thickness, subcortical volumes, and cavum septum pellucidum (CSP) were analyzed using structural MRI. Australian footballers had evidence of widespread microstructural white matter damage and cortical thinning. No significant differences were found regarding subcortical volumes or CSP. These novel findings provide evidence of persisting white and gray matter abnormalities in Australian footballers with HoC, and raise concerns related to the long-term neurological health of these athletes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-07-2012
Publisher: Frontiers Media SA
Date: 02-07-2018
Publisher: Springer Science and Business Media LLC
Date: 02-11-2017
Publisher: Public Library of Science (PLoS)
Date: 18-12-2012
Publisher: Oxford University Press (OUP)
Date: 27-10-2022
Abstract: Identifying when recovery from a sports-related concussion (SRC) has occurred remains a challenge in clinical practice. This study investigated the utility of ocular motor (OM) assessment to monitor recovery post-SRC between sexes and compared to common clinical measures. From 139 preseason baseline assessments (i.e. before they sustained an SRC), 18 (12 males, 6 females) consequent SRCs were sustained and the longitudinal follow-ups were collected at 2, 6, and 13 days post-SRC. Participants completed visually guided, antisaccade (AS), and memory-guided saccade tasks requiring a saccade toward, away from, and to a remembered target, respectively. Changes in latency (processing speed), visual–spatial accuracy, and errors were measured. Clinical measures included The Sports Concussion Assessment Tool, King-Devick test, Stroop task, and Digit span. AS latency was significantly longer at 2 days and returned to baseline by 13-days post-SRC in females only (P & 0.001). Symptom numbers recovered from 2 to 6 days and 13 days (P & 0.05). Persistently poorer AS visual–spatial accuracy was identified at 2, 6 and 13 days post-SRC (P & 0.05) in both males and females but with differing trajectories. Clinical measures demonstrated consistent improvement reminiscent of practice effects. OM saccade assessment may have improved utility in tracking recovery compared to conventional measures and between sexes.
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2017
DOI: 10.1101/208751
Abstract: The white matter is highly vascularised by the cerebral venous system. The neuroinflammatory disease multiple sclerosis is associated with infiltration of peripheral immune cells into the brain via these vessels. Understanding venous pathophysiology in multiple sclerosis is thus critical for understanding early disease aetiology. In this paper, we describe a unique blood oxygen-level dependent (BOLD) signal within the white matter using functional MRI and spatial independent components analysis, a blind signal source separation method. The signal was characterised by a narrow peak frequency band between 0.05 and 0.1 Hz. Hypercapnia (transient breath holds), known to alter venous calibre in cortex, induced transient increases in white matter BOLD that disrupted the oscillation indicative of a vasodilatory/contractile mechanism. Comparison of the white matter BOLD oscillations between age and sex matched groups of 18 multiple sclerosis and 14 healthy participants revealed a loss of power in the white matter BOLD signal in the peak frequency band (patients = 6.70±0.94 dB/Hz vs controls = 7.64±0.71 dB/Hz p=0.006). In multiple sclerosis patients, lower power was associated with greater levels of neuroinflammatory activity (R=−0.64, p=0.006) but not neurodegenerative disease markers. Using a signal modelling technique, we assessed the anatomical distribution of white matter BOLD signal abnormalities and detected reduced power in the periventricular white matter, a region of known venous damage in multiple sclerosis patients. These results demonstrate a novel link between neuroinflammation and vascular physiological dysfunction in the cerebral white matter, and could indicate enduring loss of vascular compliance associated with imperfect repair of blood-brain barrier damage after resolution of acute neuroinflammation.
Publisher: Springer Science and Business Media LLC
Date: 18-06-2020
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JNEUMETH.2018.09.022
Abstract: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 s les of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.
Publisher: Public Library of Science (PLoS)
Date: 18-09-2012
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.MSARD.2019.101522
Abstract: The assessment of cognitive information processing speed (IPS) is complicated in MS, with altered performance on tests such as the Symbol Digit Modalities Test (SDMT) potentially representing changes not only within cognitive networks but in the initial sensorial transmission of information to cognitive networks, and/or efferent transmission of the motor response. We aimed to isolate and characterise cognitive IPS deficits in MS using ocular motor tasks a prosaccade task (used to assess and control for sensorial and motor IPS) which was then used to adjust performance on the Simon task (cognitive IPS). All participants (22 MS patients with early disease, 22 healthy controls) completed the ocular motor tasks and the SDMT. The Simon task assessed cognitive IPS by manipulating the relationship between a stimulus location and its associated response direction. Two trial types were interleaved: (1) congruent, where stimulus location = response direction or (2) incongruent, where stimulus location ≠ response direction. RESULTS MS patients did not perform differently to controls on the SDMT. For OM tasks, when sensorial and motor IPS was controlled, MS patients had significantly slower cognitive IPS (incongruent trials only) and poorer conflict resolution. SDMT performance did not correlate with slower cognitive IPS in MS patients, highlighting the limitation of using SDMT performance to interpret cognitive IPS changes in patients with MS. Cognitive IPS deficits in MS patients are dissociable from changes in other processing stages, manifesting as impaired conflict resolution between automatic and non-automatic processes. Importantly, these results raise concerns about the SDMT as an accurate measure of cognitive IPS in MS.
Location: Australia
Start Date: 2011
End Date: 2013
Funder: National Multiple Sclerosis Society
View Funded ActivityStart Date: 2013
End Date: 2013
Funder: University of Melbourne
View Funded ActivityStart Date: 2013
End Date: 2013
Funder: Melbourne Research, University of Melbourne
View Funded ActivityStart Date: 2023
End Date: 12-2029
Amount: $34,948,820.00
Funder: Australian Research Council
View Funded Activity