Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA, revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep

An Interpretable Machine Learning Model to Predict Cortical Atrophy in Multiple Sclerosis

To date, the relationship between central hallmarks of multiple sclerosis (MS), such as white matter (WM)/cortical demyelinated lesions and cortical gray matter atrophy, remains unclear. We investigated the interplay between cortical atrophy and individual lesion-type patterns that have recently emerged as new radiological markers of MS disease progression. We employed a machine learning model to predict mean cortical thinning in whole-brain and single hemispheres in 150 cortical regions using demographic and lesion-related characteristics, evaluated via an ultrahigh field (7 Tesla) MRI. We found that (i) volume and rimless (i.e., without a "rim" of iron-laden immune cells) WM lesions, patient age, and volume of intracortical lesions have the most predictive power; (ii) WM lesions are more important for prediction when their load is small, while cortical lesion load becomes more important as it increases; (iii) WM lesions play a greater role in the progression of atrophy during the latest stages of the disease. Our results highlight the intricacy of MS pathology across the whole brain. In turn, this calls for multivariate statistical analyses and mechanistic modeling techniques to understand the etiopathogenesis of lesions

Neurophysiological and functional MRI evidence of reorganization of cortical motor areas in cerebral arteriovenous malformation

Functional magnetic resonance imaging (fMRI) research has shown that brain arteriovenous malformations (AVMs) lead to reorganization of cortical motor areas. Since it is known that blood oxygenation level-dependent signal in fMRI may be influenced by the hemodynamic perturbation associated with the presence of the AVM, in the present study, a combined exploration with fMRI and transcranial magnetic stimulation was performed in a patient with a right rolandic AVM in order to explore the relationship between neuronal and hemodynamic activity. The combined protocol of investigation adopted in this study was able to provide significant information regarding neuronal activity of the different cortical areas that partake to post-lesional reorganization

Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis

On the basis of recent functional MRI studies, Multiple Sclerosis (MS) has been interpreted as a multisystem disconnection syndrome. Compared to normal subjects, MS patients show alterations in functional connectivity (FC). However, the mechanisms underlying these alterations are still debated. The aim of the study is to investigate resting state (RS) FC changes after initial treatment with fingolimod, a proven anti-inflammatory and immunomodulating agent for MS. We studied 32 right-handed relapsing-remitting MS patients (median Expanded Disability Status Scale: 2.0, mean disease duration: 8.8 years) who underwent both functional and conventional MRI with a 3 Tesla magnet. All assessments were performed 3 weeks before starting fingolimod, then, at therapy-initiation stage and at month 6. Each imaging session included scans at baseline (run1) and after (run2) a 25-min, within-session, motor-practice task, consisting of a paced right-thumb flexion. FC was assessed using a seed on the left primary motor cortex to obtain parametric maps at run1 and task-induced FC change (run2-run1). Comparison between 3-week before- and fingolimod start sessions accounted for a test-retest effect. The main outcome was the changes in both baseline and task-induced changes in FC, between initiation and 6 months. MRI contrast enhancement was detected in 14 patients at initiation and only in 3 at month 6. There was a significant improvement (p < 0.05) in cognitive function, as measured by the Paced Auditory Serial Addition Task, at month 6 compared to initiation. After accounting for test-retest effect, baseline FC significantly decreased at month 6, with respect to initiation (p < 0.05, family-wise error corrected) in bilateral occipito-parietal areas and cerebellum. A task-induced change in FC at month 6 showed a significant increment in all examined sessions, involving not only areas of the sensorimotor network, but also posterior cortical areas (cuneus and precuneus) and areas of the prefrontal and temporal cortices (p < 0.05, family-wise error corrected). Cognitive improvement at month 6 was significantly (p < 0.05) related to baseline FC reduction in posterior cortical areas. This study shows significant changes in functional connectivity, both at baseline and after the execution of a simple motor task following 6 months of fingolimod therapy

Neuroinflammation, neurodegeneration and regeneration in multiple sclerosis: intercorrelated manifestations of the immune response

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory-demyelinating disorder of the central nervous system, with a strong neurodegenerative component. The question whether neurodegeneration in MS is independent or related to neuroinflammation has been long debated, but not yet fully clarified. Furthermore, little is still known on how neuroinflammation and neurodegeneration in MS are related to potential regenerative processes. In this perspective, we briefly discuss main clinical, pathological and experimental evidence on the relationship between neuroinflammation and neurodegeneration in MS, and on their connection with regeneration. We discuss that these processes in MS might represent intercorrelated manifestations of the immune response, especially of the innate immunity

Functional brain reorganization in multiple sclerosis: Evidence from fMRI studies

In patients with multiple sclerosis (MS), the severity of clinical signs is not closely related to indices of structural brain damage provided by conventional magnetic resonance MR. Accordingly, patients with MS may show symptom recovery while progressively accumulating tissue damage. Changes in functional organization of the cerebral cortex have been reported in functional magnetic resonance (fMRI) studies that have compared the activation patterns during motor, visual, and cognitive tasks of patients with MS with those of healthy controls. fMRI studies on MS have provided the results that are difficult to compare and may be discrepant because of differences in the criteria used for patient selection, the activation paradigm, the experimental design, and the MR acquisition parameters. Nevertheless, they do provide a new, interesting tool that sheds light on how the brain changes its functional organization in response to MS. In patients with MS, functional brain reorganization mainly consists of an increase in the extent of activation of the brain areas used by healthy subjects, as well as the recruitment of additional brain areas. These findings have been interpreted as adaptive or compensatory mechanisms that allow normal performance despite neural damage or loss. However, brain functional activity may also change in response to clinical disability, though the precise role of brain functional changes in MS has yet to fully undersand. Longitudinal studies designed to explore the effects of both rehabilitation and pharmacological agents on brain plasticity might shed light on this issue

Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine

Objective: The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine