Changes in brain perfusion with training-related visuomotor improvement 1 in MS

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. A better understanding of the mechanisms supporting brain plasticity in MS would help to develop targeted interventions to promote recovery. A total of 29 MS patients and 19 healthy volunteers underwent clinical assessment and multi-modal MRI acquisition [fMRI during serial reaction time task (SRT), DWI, T1w structural scans and ASL of resting perfusion] at baseline and after 4-weeks of SRT training. Reduction of functional hyperactivation was observed in MS patients following the training, shown by the stronger reduction of the BOLD response during task execution compared to healthy volunteers. The functional reorganization was accompanied by a positive correlation between improvements in task accuracy and the change in resting perfusion after 4 weeks’ training in right angular and supramarginal gyri in MS patients. No longitudinal changes in WM and GM measures and no correlation between task performance improvements and brain structure were observed in MS patients. Our results highlight a potential role for CBF as an early marker of plasticity, in terms of functional (cortical reorganization) and behavioral (performance improvement) changes in MS patients that may help to guide future interventions that exploit preserved plasticity mechanisms

Tractography in the presence of multiple sclerosis lesions

Accurate anatomical localisation of specific white matter tracts and the quantification of their tract-specific microstructural damage in conditions such as multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease evolution and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithm’s tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvolution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious streamlines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesions on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass through areas with a high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the cortico-spinal tracts and arcuate fasciculi could be reconstructed in more than 90% of individuals. Comparing tract-specific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we show that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between r=.53 ( p<.001 ) for radial diffusivity in the right cortico-spinal tract and r=.97 ( p<.001 ) for magnetisation transfer ratio in the arcuate fasciculi. Our results show that MS white matter lesions impact fibre orientation reconstructions but this does not appear to hinder the ability to anatomically reconstruct white matter tracts in MS. Individual tract segmentation in MS is feasible on a large scale and could prove a powerful tool for investigating diagnostic and prognostic markers

Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 ± 6.10 vs. 48.90 ± 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 ± 17.31 vs. 136.49 ± 14.48 μmol/100g/min p<0.001) and DC (2.70 ± 0.51 vs. 3.18 ± 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 ± 0.09 vs. 0.39 ± 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression

Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p < 0.001) and DC (p = 0.002), and increased PmO2 (p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb (p = 0.389), OEF (p = 0.358), or GM volume (p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration

Emotion regulation and mentalization in people at risk for food addiction

We investigated the association among food addiction, difficulties in emotion regulation, and mentalization deficits in a sample of 322 Italian adults from the general population. All participants were administered the Italian versions of the Yale Food Addiction Scale (I-YFAS), the Difficulties in Emotion Regulation Scale, the Mentalization Questionnaire, the Binge Eating Scale, and the Michigan Alcohol Screening Test. Over 7 percent (7.1%) of the respondents reported high food addiction symptoms (i.e., 3 or more symptoms of food addiction on the I-YFAS). In the bivariate analyses, high food addiction symptoms were associated with more difficulties in emotion regulation and mentalization deficits. In the multivariate analysis, high food addiction symptoms remained independently associated with mentalization deficits, but not with difficulties in emotion regulation. Our data suggests that mentalization may play an important role in food addiction by making it difficult for an individual to understand his/her inner own mental states as well as the mental states of others, especially when powerful emotions arise

Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume