No abstract

Fronto-parietal regions are involved in cognitive processes that are commonly affected in Parkinson's disease (PD). The aims of this study were to investigate cerebral blood flow (CBF) and gray matter (GM) volume within the regions belonging to the fronto-parietal circuit in people with PD (pwPD) without dementia, and to assess their association with cognitive performance. Twenty-seven pwPD without dementia (mean [SD] age = 67.4 [8.1] years, 20 males, mean [SD] Montreal Cognitive Assessment, MoCA score = 24.2 [2.9], median [IQR] Hoehn and Yahr scale = 1.5 [1-2]) and twenty-six age-and sex-matched healthy controls (HC) were scanned with arterial spin labeling (ASL) and T1-weighted magnetic resonance imaging (MRI) sequences to investigate CBF and GM volume, respectively. The cognitive performance of the enrolled pwPD was assessed with MoCA, Trail Making Test (TMT, part A, B, B-A), phonemic fluency and semantic fluency tests. The scores were adjusted for age and education. After standard preprocessing, CBF differences between pwPD and HC were tested with a voxel-wise approach. Voxel-based morphometry was used to compare pwPD and HC in terms of GM volume. Both voxel-wise comparisons between pwPD and HC were restricted to regions of the fronto-parietal circuit. The following additional voxel-wise analyses were performed within regions showing either perfusion or GM volume alterations: (1) correlation with neuropsychological test scores; (2) subgroup comparison after median split on each neuropsychological test score. Family-wise error-corrected (FWE) p-values lower than 0.05 were considered significant. Significant hypoperfusion was identified in the left inferior parietal lobule (IPL, p peak = 0.037) and in the bilateral superior parietal lobule (SPL, left hemisphere: p peak = 0.037; right hemisphere: p peak = 0.049) of pwPD when compared to HC. No significant GM atrophy was observed. Local hypoperfusion did not correlate with any neuropsychological test scores. However, significantly lower CBF was observed in the left SPL and IPL of the pwPD subgroup who performed poorer on TMT part A in comparison with the pwPD subgroup that performed better. Perfusion alterations may occur in parietal regions of pwPD without dementia, and may be associated with lower visuomotor skills. Parietal CBF may be considered as a suitable early biomarker for longitudinal studies investigating cognitive decline in PD.

Background: Little is still known about the mid/long-term effects of coronavirus disease 2019 (COVID-19) on the brain, especially in subjects who have never been hospitalized due to the infection. In this neuroimaging exploratory study, we analyzed the medium-term effect of COVID-19 on the brain of people who recovered from COVID-19, experienced anosmia during the acute phase of the disease, and have never been hospitalized due to SARS-Co-V-2 infection. Methods: Forty-three individuals who had (COV+, n = 22) or had not (COV−, n = 21) been infected with SARS-Co-V-2 were included in the study; the two groups were age- and sex-matched and were investigated using 3T magnetic resonance imaging (MRI). Gray matter (GM) volume, white matter (WM) hyperintensity volume, WM microstrutural integrity (i.e. fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) and cerebral blood flow (CBF) differences between the two groups were tested with either analysis of covariance or voxel-wise analyses. Results were family wise error (FWE) corrected. Results: No significant differences between COV+ and COV− groups were observed in terms of GM volume, WM hyperintensity volume, and CBF. Conversely, local WM microstructural alterations were detected in COV+ when compared with COV− with tract-based spatial statistics. Specifically, COV+ showed lower FA (pFWE-peak = 0.035) and higher RD (pFWE-peak = 0.038) than COV− in several WM regions. Conclusion: COVID-19 may produce mid/long-term microstructural effect on the brain, even in case of mild-to-moderate disease not requiring hospitalization. Further investigation and additional follow-ups are warranted to assess if the alterations reported in this study totally recover over time. As brain alterations could increase the risk of cognitive decline, greater knowledge of their trajectories is crucial to aid neurorehabilitation treatments.

Early life adversity (ELA) in childhood is a major risk factor for borderline intellectual functioning (BIF). BIF affects both adaptive and intellectual abilities, commonly leading to school failure and to an increased risk to develop mental and social problems in the adulthood. This study aimed to investigate the neurobiological underpinnings of ELA associated with BIF in terms of global topological organization and structural connectivity and their relation with intellectual functioning. BIF (N=32) and age-matched typical development (TD, N=14) children were evaluated for intelligence quotient (IQ), behavioral competencies, and ELA. Children underwent an anatomical and diffusionweighted MR imaging (DWI) protocol. Global brain topological organization was assessed measuring segregation and integration indexes. Moreover, structural matrices, measuring normalized number of fibers (NFn), were compared between the 2 groups using networkbased statistics. Finally, a linear regression model was used to explore the relationship between network parameters and clinical measures. Results showed increased behavioral difficulties and ELA, together with decreased network integration in BIF children. Moreover, significantly lower NFn was observed in the BIF group (p=.039) in a sub-network comprising anterior and posterior cingulate, the pericallosal sulcus, the orbital frontal areas, amygdala, basal ganglia, the accumbens nucleus, and the hippocampus. Linear regression showed that NFn significantly predicted IQ (p<.0001). This study demonstrated that ELA in children with BIF is associated with a decreased information integration at the global level, and with an altered structural connectivity within the limbic system strictly related to the intellectual functioning.

Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) and arterial spin labeling (ASL) datasets on a group of 26 early PD (66.8 ± 8 years, 22 males, median [interquartile range] Hoehn and Yahr = 1.5 [1]) and 18 age- and sex-matched healthy controls (HCs). In addition, a T1-weighted MPRAGE was also acquired in the same scan session. After a standard preprocessing, resting state networks (RSNs) and CBF maps were extracted from rsfMRI and ASL dataset, respectively. Then, by means of a dual regression algorithm performed on RSNs, a cluster of FC differences between groups was obtained and used to mask CBF maps in the subsequent voxel-wise group comparison. Furthermore, a gray matter (GM) volumetric assessment was performed within the FC cluster in order to exclude tissue atrophy as a source of functional changes. Reduced FC for a PD patient with respect to HC group was found within a sensory-motor network (SMN, p FWE = 0.01) and visual networks (VNs, primary p FWE = 0.022 and lateral p FWE = 0.01). The latter was accompanied by a decreased CBF (primary p FWE = 0.037, lateral p FWE = 0.014 VNs), while no GM atrophy was detected instead. The FC alteration found in the SMN of PD might be likely due to a dopaminergic denervation of the striatal pathways causing a functional disconnection. On the other hand, the changes in connectivity depicted in VNs might be related to an altered non-dopaminergic system, since perfusion was also reduced, revealing a compromised NVC. Finally, the absence of GM volume loss might imply that functional changes may potentially anticipate neurodegeneration. In this framework, FC and CBF might be proposed as early functional biomarkers providing meaningful insights in evaluating both disease progression and therapeutic/rehabilitation treatment outcome.

Parkinson’s disease (PD) is the second most common neurological disease affecting the elderly population. Pharmacological and surgical interventions usually employed for PD treatment show transient effectiveness and are associated with the insurgence of side effects. Therefore, motor rehabilitation has been proposed as a promising supplement in the treatment of PD, reducing the global burden of the disease and improving patients quality of life. The present systematic review aimed to critically analyse the literature concerning MRI markers of brain functional and structural response to motor rehabilitation in PD. Fourteen out of 1313 studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Despite the limited number of retrieved studies coupled with their heterogeneity prevent ultimate conclusions from being drawn, motor rehabilitation seems to have beneficial effects on PD as measured both with clinical outcomes and MRI derived indices. Interestingly, consistent results seem to indicate that motor rehabilitation acts via a dual mechanism of strengthening cortico-subcortical pathways, restoring movements automaticity, or activating compensatory networks such as the fronto-parietal one. The employment of more advanced and quantitative MRI methods is warranted to establish and validate standardized metrics capable of reliably determining the changes induced by rehabilitative intervention.

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures.

Background: Motor rehabilitation is routinely used in clinical practice as an effective method to reduce progressive disability gain in multiple sclerosis (MS), but rehabilitation approaches are typically unstandardized, and only few studies have investigated the impact of rehabilitation on brain neuroplasticity.Objective: To summarize and critically analyze studies applying MRI markers of functional connectivity and structural changes to assess the effect of motor rehabilitation on brain neuroplasticity in MS.Methods: Literature search was performed using PubMed and EMBASE, selecting studies having as a subject motor rehabilitation and advanced MRI techniques investigating neuroplasticity in adult patients affected by MS.Results: Seventeen out of 798 papers were selected, of which 5 applied structural MRI (4 diffusion tensor imaging, 1 volumetric measurements), 7 applied functional fMRI (5 task-related fMRI, 2 resting-state fMRI) whereas the remaining 5 applied both structural and functional imaging.Discussion: The considerable data heterogeneity and the small sample sizes characterizing the studies limit interpretation and generalization of the results. Overall, motor rehabilitation promotes clinical improvement, paralleled by positive adaptive brain changes, whose features and extent depend upon different variables, including the type of rehabilitation approach. MRI markers of functional and structural connectivity should be implemented in studies testing the efficacy of motor rehabilitation. They allow for a better understanding of neuroplastic mechanisms underlying rehabilitation-mediated clinical achievements, facilitating the identification of rehabilitation strategies tailored to patients' needs and abilities.