To explore the relationship between cognitive impairment and conventional measures of disability in multiple sclerosis (MS), quality of life (QOL) and employment status using the brief international ...cognitive assessment for multiple sclerosis (BICAMS) in the routine outpatient clinic.
62 patients with MS were assessed on the BICAMS test battery for cognitive impairment. Data were obtained on employment status and a number of questionnaires completed including fatigue severity score, multiple sclerosis neuropsychological questionnaire, hospital anxiety and depression scale, the functional assessment of multiple sclerosis (FAMS) as well as on the EuroQOL five dimension questionnaire (EQ-5D). Other assessments include the patient activation measure and unidimensional self-efficacy scale for multiple sclerosis.
Cognitive assessment revealed 44 subjects (65%) had evidence of cognitive impairment on formal testing. In comparison with patients without evidence of cognitive impairment, cognitively impaired patients exhibited significantly higher rates of unemployment (p=0.009). The symbol digits modalities test was the most significant predictor of unemployment. Cognitive impairment was associated with lower QOL scores on the FAMS (p=0.001) and EQ-5D (p<0.001).
BICAMS provides a sensitive and easy to administer screening test for cognitive impairment within the outpatient setting. Cognitive impairment is common in our cohort of patients with MS attending outpatients and appears to be associated with increased rates of unemployment and lower measures of QOL.
To assess the contribution of regional grey matter (GM) atrophy and functional disconnection in determining the level of cognitive decline in patients with Alzheimer's disease (AD) at different ...clinical stages.
Ten patients with amnesic mild cognitive impairment (a-MCI), 11 patients with probable AD and 10 healthy controls were recruited. T1 volumes were obtained from each subject and postprocessed according to an optimised voxel based morphometry protocol. Resting state functional MRI data were also collected from the same individuals and analysed to produce connectivity maps after identification of the default mode network (DMN) by independent component analysis.
Compared with healthy controls, both AD and a-MCI patients showed a similar regional pattern of brain disconnection between the posterior cingulate cortex (PCC) and the medial prefrontal cortex and the rest of the brain. Conversely, the distribution of GM atrophy was significantly more restricted in a-MCI than in AD patients. Interestingly, the PCC showed reduced connectivity in a-MCI patients in the absence of GM atrophy, which was, in contrast, detectable at the stage of fully developed AD.
This study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.
The hippocampus is a morphologically complex region of the brain limbic system centrally involved in important cognitive, affective, and behavioural regulatory roles. It has exquisite vulnerability ...to neuroinflammatory processes, with some of its subregions found to be specific sites of neuroinflammatory pathology in ex-vivo studies. Optimizing neuroimaging correlates of hippocampal neuroinflammation would enable the direct study of functional consequences of hippocampal neuroinflammatory pathology, as well as the definition of therapeutic end-points for treatments targeting neuroinflammation, and their related affective or cognitive sequelae. However, in vivo traditional imaging of the hippocampus and its subregions is fraught with difficulties, due to methodological challenges deriving from its unique anatomical characteristics. The main objective of this review is to provide a current update on the characterization of quantitative neuroimaging correlates of hippocampal neuroinflammation by focusing on three prototypical autoimmune neuro-inflammatory conditions multiple sclerosis (MS), systemic lupus erythematosus (SLE), and autoimmune encephalitis (AE). We focused on studies employing TSPO-targeting positron emission tomography (PET), quantitative magnetic resonance imaging (MRI), and spectroscopy techniques assumed to be sensitive to neuroinflammatory tissue changes. We found 18 eligible studies (14, 2, and 2 studies in MS, AE, and SLE, respectively). Across conditions, the largest effect was seen in TSPO PET and diffusion-weighted MRI studies. No study examined neuroinflammation-related changes at the hippocampal subfield level. Overall, results were largely inconsistent due to heterogeneous imaging methods, small sample sizes, and different population studies. We discuss how these data could inform future study design and conclude by suggesting further methodological directions aimed at improving the precision and sensitivity of neuroimaging techniques to characterize hippocampal neuroinflammatory pathology in the human brain.
Introduction
The hippocampus is an important, complex limbic structure anatomically embedded in the medial temporal lobe of each cerebral cortex, which has been implicated in the pathogenesis of ...neuro-inflammatory disease conditions. Few studies have focused on the characterization of the MRI neuroimaging signatures of highly physio- pathologically relevant subfields of the hippocampus (CA1, CA4-DG, CA2/CA3, SLRM).
Objectives
Using self-guided manually segmented, Diffusion weighted and NODDI maps created from data obtained from the Human Connectome Project (HCP) we intend to test whether Diffusion MRI-based quantitative imaging parameters (MD, FA, ODI, ISOVF, ICVF), indicative of microstructural characteristics of major hippocampal subfields (CA1, CA2/CA3, CA4-DG and SLRM), correspond to predictions for animal literature and imaging-histology correlations. We will also explore the correlations between these parameters and age.
Methods
We used images from the Public connectome data (updated April 2018), exploring subjects with the 3T MRI sessions obtainable from the WU-Minn HCP Data section. For the purpose of this study, we selected and downloaded 10 preliminary imaging data (6 females and 4 males) based on age variability in the following ranges (26-30, 31-35 and 36+). We manually segmented, and computed quantitative parameters.
Results
Converging and consistent literature allude to decreasing volumes with increasing age. Analyzing the volumes from the diffusion maps (pilot data), this was also the case, with volumes computed from CA1 and DG-CA4 sub regions. IQT also allowed for better appreciation of neuroanatomical boundaries and land marks, hence allowing more regions to be easily manually segmented (addition of CA2/CA3).
Conclusions
Application to Neuroinflammatory imaging data.
Disclosure
No significant relationships.
The key component of a microstructural diffusion MRI ‘super-scanner’ is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional ...gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of ‘super-scanners’.
•Improved estimation of axon diameter in vivo.•Better fitting of complex microstructure models.•Improved characterisation of tumours.•Facilitation of multi-contrast MRI experiments.
Aim. To explore the efficacy of home-based, computerised, cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and advanced structural and functional ...magnetic resonance imaging (fMRI). Methods. 38 patients with MS and cognitive impairment on the Brief International Cognitive Assessment for MS (BICAMS) were enrolled. Patients were randomised to undergo 45 minutes of computerised cognitive rehabilitation using RehaCom software (n=19) three times weekly for six weeks or to a control condition (n=19). Neuropsychological and MRI data were obtained at baseline (time 1), following the 6-week intervention (time 2), and after a further twelve weeks (time 3). Cortical activations were explored using fMRI and microstructural changes were explored using quantitative magnetisation transfer (QMT) imaging. Results. The treatment group showed a greater improvement in SDMT gain scores between baseline and time 2 compared to the control group (p=0.005). The treatment group exhibited increased activation in the bilateral prefrontal cortex and right temporoparietal regions relative to control group at time 3 (p<0.05FWE corrected). No significant changes were observed on QMT. Conclusion. This study supports the hypothesis that home-based, computerised, cognitive rehabilitation may be effective in improving cognitive performance in patients with MS. Clinical trials registration is ISRCTN54901925.
•NODDI, was used to probe subtle changes to tissue microstructure associated with IFN-α.•We found a strong correlation between changes in neurite density index with acute and long-term fatigue ...following IFN-α.•This observation confirms that the striatum is a key brain area targeted by IFN with implications for impaired motivation.
Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. In susceptible patients, fatigue and motivational impairment emerge early and have been linked to changes in basal ganglia (striatal) metabolism, neurochemistry and microstructural integrity. Here we use neurite orientation dispersion and density imaging (NODDI) modeling of multi-shell diffusion MRI to investigate whether changes in orientation-dispersion index (ODI) or neurite density index (NDI) can predict the later emergence of IFN-α-induced fatigue. Eighteen patients initiating IFN-α-based treatment for hepatitis-C underwent diffusion MRI and blood sampling at baseline and 4 h after their first IFN-α injection. They were then followed up with regular psychological assessments for 12 weeks of treatment. IFN-α injection stimulated an acute inflammatory cytokine response and evoked acute fatigue that peaked between 4 and 12 weeks of treatment. Within the brain, IFN-α induced an acute increase in NDI in patients that experienced a simultaneous increase in IFN-α-induced fatigue but not in patients that did not. Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue.
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive ...impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients’ cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (
n
= 9) and controls (
n
= 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation.
Fronto-temporal dementia (FTD) is a common type of presenile dementia, characterized by a heterogeneous clinical presentation that includes three main subtypes: behavioural-variant FTD, ...non-fluent/agrammatic variant primary progressive aphasia and semantic variant PPA. To better understand the FTD subtypes and develop more specific treatments, correct diagnosis is essential. This study aimed to test the discrimination power of a novel set of cortical Diffusion Tensor Imaging measures (DTI), on FTD subtypes. A total of 96 subjects with FTD and 84 healthy subjects (HS) were included in the study. A "selection cohort" was used to determine the set of features (measurements) and to use them to select the "best" machine learning classifier from a range of seven main models. The selected classifier was trained on a "training cohort" and tested on a third cohort ("test cohort"). The classifier was used to assess the classification power for binary (HS vs. FTD), and multiclass (HS and FTD subtypes) classification problems. In the binary classification, one of the new DTI features obtained the highest accuracy (85%) as a single feature, and when it was combined with other DTI features and two other common clinical measures (grey matter fraction and MMSE), obtained an accuracy of 88%. The new DTI features can distinguish between HS and FTD subgroups with an accuracy of 76%. These results suggest that DTI measures could support differential diagnosis in a clinical setting, potentially improve efficacy of new innovative drug treatments through effective patient selection, stratification and measurement of outcomes.
Visuospatial abilities are preferentially mediated by the right hemisphere. Although this asymmetry of function is thought to be due to an unbalanced interaction between cerebral hemispheres, the ...underlying neurophysiological substrate is still largely unknown. Here, using a method of trifocal transcranial magnetic stimulation, we show that the right, but not left, human posterior parietal cortex exerts a strong inhibitory activity over the contralateral homologous area by a short-latency connection. We also clarify, using diffusion-tensor magnetic resonance imaging, that such an interaction is mediated by direct transcallosal projections located in the posterior corpus callosum. We argue that this anatomo-functional network may represent a possible neurophysiological basis for the ongoing functional asymmetry between parietal cortices, and that its damage could contribute to the clinical manifestations of neglect.
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