Giulia Bommarito

Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis.

Objective: To evaluate the neural basis of subjective fatigue in subjects with multiple sclerosis (MS) using a connectionist framework. Methods: Seventy seven subjects with relapsing–remitting MS were recruited in the study and underwent subjective fatigue evaluations and a diffusion MRI scan. Firstly, local white matter Fractional Anisotropy values were correlated with subjective fatigue scores using a voxel-wise approach. The long-range loss of connectivity due to structural damage in the white matter voxels thus associated with subjective fatigue was then assessed using the Network Modification (NeMo) package. Results: A voxel-wise regression analysis with fatigue scores revealed a significant association between structural damage and fatigue levels in two discrete white matter clusters, both included in the left cingulate bundle. The connectivity analysis revealed that damage in these clusters was associated with loss of structural connectivity in the anterior and medial cingulate cortices, dorsolateral prefrontal areas and in the left caudate. Discussion: Our data point to the cingulum bundle and its projections as the key network involved in subjective fatigue perception in MS. More generally, these results suggest the potential of the connectionist framework to generate coherent models of the neural basis of complex symptomatology in MS.

Resting-state functional connectivity and motor imagery brain activation

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting‐state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting‐state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel‐matched correlation between the individual MI parameter estimates and seed‐based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter‐individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847–3857, 2016.

Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique’s advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.

Composite MRI measures and short-term disability in patients with clinically isolated syndrome suggestive of MS:

Background: The use of composite magnetic resonance imaging (MRI) measures has been suggested to better explain disability in patients with multiple sclerosis (MS). However, little is known about the utility of composite scores at the earliest stages of the disease. Objective: To investigate whether, in patients with clinically isolated syndrome (CIS), a composite MRI measure, rather than the single metrics, would explain conversion to MS and would better correlate with disability at baseline and at 1 year of follow-up. Methods: Corticospinal tract (CST), corpus callosum (CC) and optic radiation (OR) volume, fractional anisotropy (FA), and mean diffusivity (MD) values were measured in 27 CIS patients and 24 healthy controls (HCs). Z-scores of FA, MD, and tract volume measures were calculated in patients, based on the corresponding measures obtained from HCs, and then combined in a composite score for each tract. Correlations between Z-scores at baseline and both the Expanded Disability Status Scale (EDSS) at baseline and at follow-up (FU-EDSS) were investigated. Results: Only CST, CC, and OR composite scores as well as the CST volume were significantly associated with FU-EDSS (p = 0.005, p = 0.007, p = 0.020, and p = 0.010, respectively). Conclusion: The combination of MRI measures rather than the individual metrics better captured the association between tissue damage in both the CC, OR and CST and short-term follow-up disability.

Neural correlates of lower limbs proprioception: An fMRI study of foot position matching

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right‐handed and right‐footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.

Exploring mania-associated white matter injury by comparison with multiple sclerosis: a diffusion tensor imaging study

Bipolar disorder (BD), especially in its active phases, has shown some neuroimaging and immunological similarities with multiple sclerosis (MS). The objective of this study was to compare white matter (WM) alterations in BD patients in manic phase (M-BD) and MS patients at early stage of disease and with low lesion burden. We compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) in a priori selected WM regions (i.e., corpus callosum and cingulum) betwixt 23 M-BD, 23 MS patients and 46 healthy controls. Both M-BD and MS showed WM changes in the corpus callosum, which, however, showed a greater impairment in MS patients. However, considering the different sub-regions of corpus callosum separately (i.e., genu, body, splenium), M-BD and MS presented an opposite pattern in spatial distribution of WM microstructure alterations, with a greater impairment in the anterior region in M-BD and in the posterior region in MS. Common features as well as divergent patterns in DTI changes are detected in M-BD and early MS, prompting a deeper investigation of analogies and differences in WM and immunological alterations of these disorders.

Monitoring Progressive Multiple Sclerosis with Novel Imaging Techniques

Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques.

Motor Imagery as a Function of Disease Severity in Multiple Sclerosis: An fMRI Study

Motor imagery (MI) is defined as mental execution without any actual movement. While healthy adults usually show temporal equivalence, i.e., isochrony, between the mental simulation of an action and its actual performance, neurological disorders are associated with anisochrony. Unlike in patients with stroke and Parkinson disease, only a few studies have investigated differences of MI ability in multiple sclerosis (MS). However, the relationship among disease severity, anisochrony and brain activation patterns during MI has not been investigated yet. Here, we propose to investigate MI in MS patients using fMRI during a behavioral task executed with dominant/non-dominant hand and to evaluate whether anisochrony is associated with disease severity. Thirty-seven right-handed MS patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC) underwent fMRI during a motor task consisting in the actual or imaged movement of squeezing a foam ball with the dominant and non-dominant hand. The same tasks were performed outside the MRI room to record the number of actual and imagined ball squeezes, and calculate an Index of performance (IP) based on the ratio between actual and imagined movements. IP showed that a progressive loss of ability in simulating actions (i.e., anisochrony) more pronounced for non-dominant hand, was found as function of the disease course. Moreover, anisochrony was associated with activation of occipito-parieto-frontal areas that were more extensive at the early stages of the disease, probably in order to counteract the changes due to MS. However, the neural engagement of compensatory brain areas becomes more difficult with more challenging tasks, i.e., dominant vs. non-dominant hand, with a consequent deficit in behavioral performance. These results show a strict association between MI performance and disease severity, suggesting that, at early stages of the disease, anisochrony in MI could be considered as surrogate behavioral marker of MS severity.

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Lastly, cortical lesions were assessed on phase-sensitive inversion recovery (PSIR) images and cortical thickness was quantified on volumetric T1 images. Our main result was the observation in the PPMS group of a significant correlation between periventricular NAWM MD values and cortical lesion load, with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation between cortical lesion load and deep NAWM MD values or periventricular WM lesions. Our data thus suggest that a common – and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS.

Neural correlates of ankle movements during different motor tasks: A feasibility study.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.