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Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology., Competing Interests: MM, AK, JC, MC, TN, NS No competing interests declared, (© 2020, Mancini et al.)

Ex vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of whole human hemispheres from two donors.

Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Graph-theoretical approaches have become a popular way to model brain data collected using magnetic resonance imaging (MRI), both from the structural and the functional perspectives. In structural networks, tract-based mapping allows to model different aspects of brain structures by means of the specific characteristics of the different MRI modalities. However, there has been little effort to join the information carried by each modality and to understand what level of common variance is shown in these data. In this paper, we proposed a combined approach based on graph theory and factor analysis to model magnetization transfer and microstructural properties in 18 relapsing remitting multiple sclerosis (RRMS) patients and 17 healthy controls. After defining the common factors and outlining their relationships with MRI data, we evaluated between-group differences using global and local graph measures. The results showed that one common factor describes brain structures in terms of myelin and global integrity, and such factor is able to highlight specific between-group differences.

The static magnetic field generated by MRI systems is highly non-homogenous and rapidly decreases when moving away from the bore of the scanner. Consequently, the movement around the MRI scanner is equivalent to an exposure to a time-varying magnetic field at very low frequency (few Hz). For patients with an implanted cardiac stimulators, such as an implantable cardioverter/defibrillator (ICD), the movements inside the MRI environment may thus induce voltages on the loop formed by the leads of the device, with the potential to affect the behavior of the stimulator. In particular, the ICD's detection algorithms may be affected by the induced voltage and may cause inappropriate sensing, arrhythmia detections, and eventually inappropriate ICD therapy.We performed in-vitro measurements on a saline-filled humanshaped phantom (male, 170 cm height), equipped with an MRconditional ICD able to transmit in real-time the detected cardiac activity (electrograms). A biventricular implant was reproduced and the ICD was programmed in standard operating conditions, but with the shock delivery disabled. The electrograms recorded in the atrial, left and right ventricle channels were monitored during rotational movements along the vertical axis, in close proximity of the bore. The phantom was also equipped with an accelerometer and a magnetic field probe to measure the angular velocity and the magnetic field variation during the experiment. Pacing inhibition, inappropriate detection of tachyarrhythmias and of ventricular fibrillation were observed. Pacing inhibition began at an angular velocity of about 7 rad/s, (dB/dt of about 2 T/s). Inappropriate detection of ventricular fibrillation occurred at about 8 rad/s (dB/dt of about 3 T/s). These findings highlight the need for a specific risk assessment of workers with MR-conditional ICDs, which takes into account also effects that are generally not considered relevant for patients, such as the movement around the scanner bore.

Central autonomic control on the cardiovascular system has been widely investigated in the last decades. More recently, with the advent of brain imaging techniques, considerable effort is being spent on defining the role of specific brain areas, and their dynamic network, acting on autonomic efferents. A way to assess autonomic modulation is offered by carotid stimulation. In this work, we propose a methodology to investigate autonomic control in carotid stimulation experiments using heartbeat series in combination with fMRI imaging. We modeled cardiovascular signals using the point process model, and processed fMRI data in order to estimate independent components of correlated information. Using cross-correlation and surrogate analysis, we assessed the responsiveness of subjects to neck suction stimuli and identified stimulus-related fMRI independent components.

The static magnetic field generated by MRI systems is highly non-homogenous and rapidly decreases when moving away from the bore of the scanner. Consequently, the movement around the MRI scanner is equivalent to an exposure to a time-varying magnetic field at very low frequency (few Hz). If people with an implanted pacemaker (PM) enter the MRI room, fast movements may thus induce voltages on the loop formed by the PM lead, with the potential to modify the correct behavior of the stimulator. In this study, we performed in-vitro measurements on a human-shaped phantom, equipped with an implantable PM and with a current sensor, able to monitor the activity of the PM while moving the phantom in the MRI room. Fast rotational movements in close proximity of the bore of the scanner caused the inappropriate inhibition of the PM, programmed in VVI modality, maximum sensitivity, unipolar sensing and pacing. The inhibition occurred for a variation of the magnetic field of about 3 T/s. These findings demonstrate that great care must be paid when extending PM MRI compatibility from patients to healthcare personnel, since the safety procedures and the MRI-conditional PM programming (e.g. asynchronous stimulation or bipolar sensing) used for patients cannot be applied.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Network models based on structural connectivity have been increasingly used as the blueprint for large-scale simulations of the human brain. As the nodes of this network are distributed through the cortex and interconnected by white matter pathways with different characteristics, modeling the associated conduction delays becomes important. The goal of this study is to estimate and characterize these delays directly from the brain structure. To achieve this, we leveraged microstructural measures from a combination of advanced magnetic resonance imaging acquisitions and computed the main determinants of conduction velocity, namely axonal diameter and myelin content. Using the model proposed by Rushton, we used these measures to calculate the conduction velocity and estimated the associated delays using tractography. We observed that both the axonal diameter and conduction velocity distributions presented a rather constant trend across different connection lengths, with resulting delays that scale linearly with the connection length. Relying on insights from graph theory and Kuramoto simulations, our results support the approximation of constant conduction velocity but also show path- and region-specific differences. [ABSTRACT FROM AUTHOR]

Abstract Generalized anxiety disorder (GAD) is associated with both autonomic dysfunction, notably decreased vagally-mediated heart rate variability (vmHRV), and neurostructural abnormalities. Regional differences in brain morphometry correlate with vmHRV in healthy individuals. Here, we tested the hypothesis that specific focal abnormalities in cortical structure in GAD underpin decreased vmHRV. Adult female patients with GAD (n = 17) and matched controls (n = 18) underwent structural magnetic resonance imaging after characterization of symptoms and quantification of resting vmHRV derived from continuous pulse oximetry. Cortical reconstruction was performed using the FreeSurfer image analysis suite. A priori analysis was conducted only within brain regions involved in vagal control of heart rate. Compared to controls, patients with GAD showed cortical thinning of the (i) left rostral anterior cingulate cortex, (ii) left medial orbitofrontal cortex, and (iii) right isthmus cingulate gyrus. Significant negative relationships were identified between the severity of anxiety symptoms and cortical thickness of the left medial orbitofrontal cortex and right isthmus cingulate gyrus. Compared to controls, patients with GAD showed decreased vmHRV at rest. In controls only, cortical thickness of the left caudal anterior cingulate cortex correlated positively with resting vmHRV. These results extend evidence in GAD for structural abnormalities within cortical areas implicated in emotion regulation and cognition. In addition, these findings may implicate abnormal integrity of anterior cingulate cortex in the psychophysiological expression of GAD and suggest that interventional targeting of this region may normalize autonomic function in GAD. Highlights • The hypothesis that autonomic dysfunction in patients with GAD is associated with brain structural changes is investigated. • Patients with GAD show reduced HRV and cortical thinning of the left rostral ACC. • Cortical thickness of the left caudal ACC correlates positively with HRV in controls, but not in patients with GAD. • Abnormal structural integrity of the ACC may be implicated in the psychophysiological expression of GAD. [ABSTRACT FROM AUTHOR]

Cognitive reserve (CR) is known to modulate the clinical features of Alzheimer's disease (AD). This concept may be critical for the development of non-pharmacological interventions able to slow down patients' cognitive decline in the absence of disease-modifying treatments. We aimed at identifying the neurobiological substrates of CR (i.e., neural reserve) over the transition between normal aging and AD, by assessing the underlying brain networks and their topological properties. A cohort of 154 participants (n = 68 with AD, n = 61 with amnestic mild cognitive impairment (aMCI), and 25 healthy subjects) underwent resting-state functional MRI and neuropsychological testing. Within each group, participants were classified as having high or low CR, and functional connectivity measures were compared, within group, between high and low CR individuals. Network-based statistics and topological network properties derived from graph theory were explored. Connectivity differences between high and low CR were evident only for aMCI patients, with participants with high CR showing a significant increase of connectivity in a network involving mainly fronto-parietal nodes. Conversely, they showed significantly decreased connectivity in a network involving fronto-temporo-cerebellar nodes. Consistently, changes to topological measures were observed in either direction, and were associated with measures of global cognitive function. These findings support the hypothesis that CR impacts on neurodegenerative process in the early phase of AD only. In addition, they fit with the existence of a "neural reserve", characterized by specific neural networks and their efficiency. It remains to be demonstrated whether interventions later in life can modulate this "neural reserve". [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients’ dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the “Reading the Mind in the Eyes” and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients’ “Theory of Mind-network”, which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients’ success in life. [ABSTRACT FROM AUTHOR]