Publications by authors named "Lazar Fleysher"

47 Publications

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis.

Brain 2021 02;144(1):213-223

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) were measured from whole brain white matter lesions and from both lesions and normal appearing white matter of the corpus callosum. Significant differences were found between T1-isointense and black holes (P ranging from 0.005 to <0.001) and between lesions' centre and rim (P < 0.001) for all the metrics. When comparing the three subject groups in terms of metrics derived from corpus callosum normal appearing white matter and T2-hyperintense lesions, a significant difference was found between healthy controls and relapsing-remitting patients for all metrics except restricted fraction and fractional anisotropy; between healthy controls and progressive patients for all metrics except restricted fraction and between relapsing-remitting and progressive multiple sclerosis patients for all metrics except fibres and restricted fractions (P ranging from 0.05 to <0.001 for all). Significant associations were found between corpus callosum normal-appearing white matter fibres fraction/non-restricted fraction and the Symbol Digit Modality Test (respectively, r = 0.35, P = 0.043; r = -0.35, P = 0.046), and between black holes radial diffusivity and Expanded Disability Status Score (r = 0.59, P = 0.002). We showed the feasibility of diffusion basis spectrum imaging metrics at 7 T, confirmed the role of the derived metrics in the characterization of lesions and normal appearing white matter tissue in different stages of the disease and demonstrated their clinical relevance. Thus, suggesting that diffusion basis spectrum imaging is a promising tool to investigate multiple sclerosis pathophysiology, monitor disease progression and treatment response.
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http://dx.doi.org/10.1093/brain/awaa381DOI Listing
February 2021

Prospective Motion Correction for Brain MRI Using an External Tracking System.

J Neuroimaging 2021 Jan 4;31(1):57-61. Epub 2020 Nov 4.

Department of Radiology, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Background And Purpose: A wide range of strategies have been developed to mitigate motion, as a major source of image quality degradation in clinical MRI. We aimed to assess the efficiency of a commercially available prospective motion correction (PMC) system in reducing motion in acquiring high-resolution 3D magnetization-prepared rapid gradient-echo (MPRAGE).

Methods: A total of 100 patients who referred for brain MRI studies were prospectively imaged using a 3.0T scanner. 3D MPRAGE acquisition was obtained with and without application of PMC. The motion tracking system (KinetiCor Inc.) consisted of a quad camera apparatus, which tracks a specific marker on patient's head by evaluating the marker's optical pattern. The patient's head motion in 6 degrees of freedom throughout the acquisition was then incorporated into the MRI sequence, updating the image acquisition in real time based on the most recent head pose data. MPRAGE images with and without motion correction were assessed independently by two board-certified neuroradiologists using a 5-point Likert scale. Statistical analysis included kappa and Wilcoxon Rank-Sum tests.

Results: Observers 1 and 2 identified nondiagnostic studies in 17.2% and 20.7% of patients (K = .78, 95% CI .70-.86) without motion correction and in 5.7% and 8% of the studies with motion correction (K = .84, 95% CI .76-.92). The number of nondiagnostic studies was significantly (P = .001) reduced from 19.5% to 5.7% after motion correction in consensus read analysis.

Conclusion: The described motion tracking system can be used effectively in clinical practice reducing motion artifact and improving image quality of 3D MPRAGE sequence.
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http://dx.doi.org/10.1111/jon.12806DOI Listing
January 2021

Laminar analysis of the cortical T1/T2-weighted ratio at 7T.

Neurol Neuroimmunol Neuroinflamm 2020 11 21;7(6). Epub 2020 Oct 21.

From the Department of Neurology (M.P., M.M.E.M., M.M., S.C., K.P., M.I.), Icahn School of Medicine at Mount Sinai, NY; Aix-Marseille Univ (M.M.E.M.), CNRS, CRMBM; APHM (M.M.E.M.), Hôpital de la Timone, CEMEREM, Marseille, France; Department of Informatics (M.M.), Bioengineering, Robotics and Systems Engineering (DIBRIS) and Machine Learning Genoa Center (MaLGa), University of Genoa; Department of Advanced Biomedical Sciences (S.C.), University of Naples "Federico II", Italy; Department of Radiology (L.F.), Icahn School of Medicine at Mount Sinai, NY; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics (M.I.), Maternal and Child Health (DINOGMI) and Center of Excellence for Biomedical Research, University of Genoa; and Ospedale Policlinico San Martino-IRCCS (M.I.), Genoa, Italy.

Objective: In this observational study, we explored cortical structure as function of cortical depth through a laminar analysis of the T1/T2-weighted (T1w/T2w) ratio, which has been related to dendrite density in ex vivo brain tissue specimens of patients with MS.

Methods: In 39 patients (22 relapsing-remitting, 13 female, age 41.1 ± 10.6 years; 17 progressive, 11 female, age 54.1 ± 9.9 years) and 21 healthy controls (8 female, , age 41.6 ± 10.6 years), we performed a voxel-wise analysis of T1w/T2w ratio maps from high-resolution 7T images from the subpial surface to the gray matter/white matter boundary. Six layers were sampled to ensure accuracy based on mean cortical thickness and image resolution.

Results: At the voxel-wise comparison ( < 0.05, family wise error rate corrected), the whole MS group showed lower T1w/T2w ratio values than controls, both when considering the entire cortex and each individual layer, with peaks occurring in the fusiform, temporo-occipital, and superior and middle frontal cortex. In relapsing-remitting patients, differences in the T1w/T2w ratio were only identified in the subpial layer, with the peak occurring in the fusiform cortex, whereas results obtained in progressive patients mirrored the widespread damage found in the whole group.

Conclusions: Laminar analysis of T1w/T2w ratio mapping confirms the presence of cortical damage in MS and shows a variable expression of intracortical damage according to the disease phenotype. Although in the relapsing-remitting stage, only the subpial layer appears susceptible to damage, in progressive patients, widespread cortical abnormalities can be observed, not only, as described before, with regard to myelin/iron concentration but, possibly, to other microstructural features.
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http://dx.doi.org/10.1212/NXI.0000000000000900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641144PMC
November 2020

Lower cortical gamma-aminobutyric acid level contributes to increased connectivity in sensory-motor regions in progressive MS.

Mult Scler Relat Disord 2020 Aug 25;43:102183. Epub 2020 May 25.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health, University of Genoa, Genoa, Italy. Electronic address:

Background: Large-scale functional abnormalities and decreased synchronization between functionally connected regions within brain networks were reported in progressive multiple sclerosis (P-MS) patients. Low concentration of gamma-aminobutyric acid (GABA) was observed in the sensorimotor cortex (SMC) of these patients and was associated with reduced motor functions of limbs. Yet, the role of GABA in modulating functional connectivity (FC) has not been investigated in MS patients.

Objectives: To determine the relationship between GABA concentration in the SMC and short-term FC changes within the sensorimotor network (SMN) in P-MS patients.

Methods: Combining magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rs-fMRI), we investigated the relationship between baseline GABA concentration in the left SMC and FC within SMN in P-MS patients compared to healthy controls (HCs). Additionally, we assessed the relationship between baseline GABA concentration and FC changes over a 1-year follow-up period in the patients' group only.

Results: At baseline, lower GABA levels, and decreased FC levels in regions within the SMN were observed in MS patients compared to healthy controls (HCs). Overtime, an increase in FC was observed in regions within the SMN in the MS group. This increase correlated inversely with motor performance scores.

Conclusions: We postulate that in P-MS patients, lower levels of GABA in the SMC contribute to decreased inhibition, and as a result, to a reactive increase of FC in inter-connected sensorimotor brain regions, thus minimizing clinical worsening.
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http://dx.doi.org/10.1016/j.msard.2020.102183DOI Listing
August 2020

Initial Evidence for Brain Plasticity Following a Digital Therapeutic Intervention for Depression.

Chronic Stress (Thousand Oaks) 2019 Jan-Dec;3:2470547019877880. Epub 2019 Sep 18.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Digital therapeutics such as cognitive-emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive-emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement.

Methods: Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing.

Results: Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement.

Discussion: These findings provide initial evidence that cognitive-emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder.

Conclusion: Our findings pave the way for the principled design of large clinical and neuroimaging studies.
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http://dx.doi.org/10.1177/2470547019877880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219906PMC
September 2019

Sensory-motor network topology in multiple sclerosis: Structural connectivity analysis accounting for intrinsic density discrepancy.

Hum Brain Mapp 2020 08 15;41(11):2951-2963. Epub 2020 May 15.

Department of Computer Science, University of Verona, Verona, Italy.

Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between-group differences disclosed by graph analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this 'COMMIT-weighted sensory-motor network' in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more 'quantitative' network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy-corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice.
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http://dx.doi.org/10.1002/hbm.24989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336144PMC
August 2020

A clinically feasible 7-Tesla protocol for the identification of cortical lesions in Multiple Sclerosis.

Eur Radiol 2020 Aug 24;30(8):4586-4594. Epub 2020 Mar 24.

Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.

Objectives: The aim of this study was to evaluate the capability of sequences acquired on a 7-T MRI scanner, within times and anatomical coverage appropriate for clinical studies, to identify cortical lesions (CLs) in patients with Multiple Sclerosis (MS). Furthermore, we aimed to confirm the clinical significance of CL, testing the correlations between gray matter (GM) lesions and clinical scores.

Methods: A 7-T MRI protocol included 3D-T1-weighted and T2*-weighted sequences. Images were evaluated independently by three readers of different experience, and the number of CLs was recorded. Between-rater concordance was assessed calculating the intraclass correlation coefficient (ICC). Lin's concordance correlation coefficient was used to compare CL detection between sequences, while partial correlations and multivariable regression models were used to study the relationship between CL and clinical data.

Results: Forty MS patients (M/F, 17/23; 44.7 ± 12.6 years) were enrolled in this study, and CLs were identified in 35/40 subjects (87.5%). CL detection rate on 3D-T1-weighted images was significantly correlated with the detection rate on T2*-weighted images (r = 0.99; p < 0.001), with high concordance between readers (ICC ≥ 0.995). CLs were significantly correlated with both motor and cognitive scores (all with p ≤ 0.04).

Conclusions: CL can be identified over the whole brain at 7-T in MS using a 3D-T1-weighted volume, acquired in a clinically feasible time and with comparable performance to that achievable using the T2*-weighted sequence. Based on the central role of CL in the development of clinical disability, we suggest that 3D-T1-weighted volume may play a role in the evaluation of CL in MS undergoing MRI on ultra-high-field scanners.

Key Points: • Cortical lesions can be identified in a clinically feasible time with a 7-T protocol, which includes a 3D-T1-weighted volume. • Cortical lesions correlated significantly with both motor and cognitive disability in MS patients. • Given their correlation with clinical disability, evaluation of a cortical lesion on a 7-T clinical protocol could help in the management of MS patients.
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http://dx.doi.org/10.1007/s00330-020-06803-yDOI Listing
August 2020

The buildup of an urge in obsessive-compulsive disorder: Behavioral and neuroimaging correlates.

Hum Brain Mapp 2020 04 9;41(6):1611-1625. Epub 2020 Jan 9.

Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York.

Obsessive-compulsive disorder (OCD) is highly heterogeneous. While obsessions often involve fear of harm, many patients report uncomfortable sensations and/or urges that drive repetitive behaviors in the absence of a specific fear. Prior work suggests that urges in OCD may be similar to everyday "urges-for-action" (UFA) such as the urge to blink, swallow, or scratch, but very little work has investigated the pathophysiology underlying urges in OCD. In the current study, we used an urge-to-blink approach to model sensory-based urges that could be experimentally elicited and compared across patients and controls using the same task stimuli. OCD patients and controls suppressed eye blinking over a period of 60 s, alternating with free blinking blocks, while brain activity was measured using functional magnetic resonance imaging. OCD patients showed significantly increased activation in several regions during the early phase of eyeblink suppression (first 30 s), including mid-cingulate, insula, striatum, parietal cortex, and occipital cortex, with lingering group differences in parietal and occipital regions during late eyeblink suppression (last 30 s). There were no differences in brain activation during free blinking blocks, and no conditions where OCD patients showed reduced activation compared to controls. In an exploratory analysis of blink counts performed in a subset of subjects, OCD patients were less successful than controls in suppressing blinks. These data indicate that OCD patients exhibit altered brain function and behavior when experiencing and suppressing the urge to blink, raising the possibility that the disorder is associated with a general abnormality in the UFA system that could ultimately be targeted by future treatments.
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http://dx.doi.org/10.1002/hbm.24898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082184PMC
April 2020

SUITer: An Automated Method for Improving Segmentation of Infratentorial Structures at Ultra-High-Field MRI.

J Neuroimaging 2020 01 5;30(1):28-39. Epub 2019 Nov 5.

Department of Neurology, Icahn School of Medicine at Mount Sinai, NY.

Background And Purpose: The advent of high and ultra-high-field MRI has significantly improved the investigation of infratentorial structures by providing high-resolution images. However, none of the publicly available methods for cerebellar image analysis has been optimized for high-resolution images yet.

Methods: We present the implementation of an automated algorithm-SUITer (spatially unbiased infratentorial for enhanced resolution) method for cerebellar lobules parcellation on high-resolution MR images acquired at both 3 and 7T MRI. SUITer was validated on five manually segmented data and compared with SUIT, FreeSurfer, and convolutional neural networks (CNN). SUITer was then applied to 3 and 7T MR images from 10 multiple sclerosis (MS) patients and 10 healthy controls (HCs).

Results: The difference in volumes estimation for the cerebellar grey matter (GM), between the manual segmentation (ground truth), SUIT, CNN, and SUITer was reduced when computed by SUITer compared to SUIT (5.56 vs. 29.23 mL) and CNN (5.56 vs. 9.43 mL). FreeSurfer showed low volumes difference (3.56 mL). SUITer segmentations showed a high correlation (R = .91) and a high overlap with manual segmentations for cerebellar GM (83.46%). SUITer also showed low volumes difference (7.29 mL), high correlation (R = .99), and a high overlap (87.44%) for cerebellar GM segmentations across magnetic fields. SUITer showed similar cerebellar GM volume differences between MS patients and HC at both 3T and 7T (7.69 and 7.76 mL, respectively).

Conclusions: SUITer provides accurate segmentations of infratentorial structures across different resolutions and MR fields.
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http://dx.doi.org/10.1111/jon.12672DOI Listing
January 2020

Functional neural mechanisms of sensory phenomena in obsessive-compulsive disorder.

J Psychiatr Res 2019 02 21;109:68-75. Epub 2018 Nov 21.

Department of Psychiatry, New York University School of Medicine, New York, NY, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA. Electronic address:

Sensory phenomena (SP) are aversive or uncomfortable sensations that accompany and/or drive repetitive behaviors in obsessive-compulsive disorder (OCD). Although SP are associated with significant distress and may respond less well to standard treatments than harm-related obsessions, little is known about their underlying neurobiology. The present study used functional magnetic resonance imaging (fMRI) to measure brain functioning related to severity of SP during a "body-focused" videos task designed to elicit activation in sensorimotor brain regions. Regression analysis examined the relationship between severity of SP and activation during task using permutation analysis, cluster-level corrected for multiple comparisons (family-wise error rate p < 0.05). The distribution of SP severity was not significantly different from normal, with both high- and low-severity scores represented in the OCD sample. Severity of SP was not correlated with other clinical symptoms in OCD including general anxiety, depression, or harm avoidance. When viewing body-focused videos, patients with greater severity of SP showed increased activity in the mid-posterior insula, a relationship that remained significant when controlling for other clinical symptoms, medication status, and comorbidities. At uncorrected thresholds, SP severity was also positively related to somatosensory, mid orbitofrontal, and lateral prefrontal cortical activity. These data suggest that SP in OCD are dissociable from other symptoms in the disorder and related to hyperactivation of the insula. Future work examining neural mechanisms of SP across different disorders (tics, trichotillomania) as well as with other imaging modalities will be needed to further understand the neurobiology of these impairing symptoms.
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http://dx.doi.org/10.1016/j.jpsychires.2018.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347462PMC
February 2019

Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

Elife 2018 11 21;7. Epub 2018 Nov 21.

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.

The brain displays a remarkable ability to adapt following injury by altering its connections through neural plasticity. Many of the biological mechanisms that underlie plasticity are known, but there is little knowledge as to when, or where in the brain plasticity will occur following injury. This knowledge could guide plasticity-promoting interventions and create a more accurate roadmap of the recovery process following injury. We causally investigated the time-course of plasticity after hippocampal lesions using multi-modal MRI in monkeys. We show that post-injury plasticity is highly dynamic, but also largely predictable on the basis of the functional connectivity of the lesioned region, gradients of cell densities across the cortex and the pre-lesion network structure of the brain. The ability to predict which brain areas will plastically adapt their functional connectivity following injury may allow us to decipher why some brain lesions lead to permanent loss of cognitive function, while others do not.
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http://dx.doi.org/10.7554/eLife.34354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249000PMC
November 2018

An Open Resource for Non-human Primate Imaging.

Neuron 2018 10 27;100(1):61-74.e2. Epub 2018 Sep 27.

Centre for Social Learning and Cognitive Evolution, School of Biology, University of St. Andrews, St. Andrews, UK.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.
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http://dx.doi.org/10.1016/j.neuron.2018.08.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231397PMC
October 2018

Development of a methodology to combine fMRI and EMG to measure emotional responses in patients with anorexia nervosa.

Int J Eat Disord 2018 07 18;51(7):722-729. Epub 2018 Aug 18.

Eating and Weight Disorders Program Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Objective: Individuals with eating disorders are theorized to have basic impairments in affective appraisal and social-emotional processing that contribute to pathogenesis of the disease. We aimed to determine if facial electromyography could be used to discriminate between happy and disgust emotions during simultaneous acquisition of an fMRI BOLD sequence in efforts to establish a novel tool for investigating emotion-driven hypotheses about eating pathology. In line with standards for rigor and reproducibility, we provide detailed protocols and code to support each step of this project.

Method: Sixteen adolescents with low-weight eating disorders viewed emotional faces (Happy or Disgust) and were asked to mimic their facial expression during simultaneous BOLD and EMG (Corrugator supercilli, Lavator lavii, Zygomaticus major) acquisition. Trials were repeated with the scanner off and again with scanner on (i.e., fatigue).

Results: The Levator and Zygomaticus activation patterns discriminated disgust and happy faces successfully. The pattern held between scanner on and off conditions, but muscle activation attenuated in the Fatigue condition, especially for the Zygomaticus.

Discussion: Simultaneous fMRI-EMG is a new tool capable of discriminating specific emotions based on muscle activation patterns and can be leveraged to answer emotion-driven hypotheses about clinical populations characterized by difficulty labeling or processing emotions.
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http://dx.doi.org/10.1002/eat.22893DOI Listing
July 2018

High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions.

Neuropsychopharmacology 2019 01 8;44(2):390-398. Epub 2018 Aug 8.

Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.

Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating interoceptive circuits could lead to novel treatment approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors are located abundantly on sensory pathways and ondansetron has shown some clinical utility in disorders characterized by sensory and interoceptive abnormalities. The present study tested the ability of three different doses of ondansetron to engage neural regions involved in interoception to determine the drug's utility as a therapeutic agent to target circuit abnormalities in patients. Fifty-three healthy subjects were randomized to receive a single 8-mg (n = 18), 16-mg (n = 17), or 24-mg (n = 18) dose of ondansetron and placebo before MRI scanning on separate days. Subjects performed an fMRI task previously shown to engage interoceptive circuitry in which they viewed videos depicting body movements/sensation and control videos. The results revealed a highly significant relationship between dosage and activation in bilateral insula, somatosensory and premotor regions, cingulate cortex, and temporal cortex for control but not body-focused videos. These effects were driven by a robust reduction in activation for ondansetron compared to placebo for the 24-mg group, with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose ondansetron reduces activation of several areas important for interoception, including insula and sensorimotor cortical regions. This study reveals the potential utility of this drug in modulating hyperactivity in these regions in patients.
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http://dx.doi.org/10.1038/s41386-018-0174-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300545PMC
January 2019

An MRI evaluation of grey matter damage in African Americans with MS.

Mult Scler Relat Disord 2018 Oct 12;25:29-36. Epub 2018 Jul 12.

Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, (DINOGMI) University of Genova and IRCCS AOU San Martino-IST, Genoa, Italy. Electronic address:

Objective: Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS.

Methods: In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs).

Results: In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs.

Interpretation: In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups.
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http://dx.doi.org/10.1016/j.msard.2018.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214725PMC
October 2018

CCR2 on Peripheral Blood CD14CD16 Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?

J Neuroimmune Pharmacol 2019 03 6;14(1):120-133. Epub 2018 Jul 6.

Departments of Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.

HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14CD16 monocytes, particularly those that are HIV infected and express increased surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14CD16 monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14CD16 monocytes with cognitive status, proton magnetic resonance spectroscopy (H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14CD16 monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14CD16 monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14CD16 monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14CD16 monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14CD16 monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.
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http://dx.doi.org/10.1007/s11481-018-9792-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320730PMC
March 2019

Clinical applications of ultra-high field magnetic resonance imaging in multiple sclerosis.

Expert Rev Neurother 2018 03 30;18(3):221-230. Epub 2018 Jan 30.

a Department of Neurology , Icahn School of Medicine , Mount Sinai , NY , USA.

Introduction: Magnetic resonance imaging (MRI) is of paramount importance for the early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS diagnostic criteria. There is a growing interest in the use of ultra-high-field strength -7 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate of the disease. Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. Implications for disease diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow higher spatial resolution and better detection of anatomical and pathological features. The high spatial resolution reachable at 7T has been a game changer for neuroimaging applications not only in MS but also in epilepsy, brain tumors, dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has recently been cleared for clinical use by the food and drug administration.
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http://dx.doi.org/10.1080/14737175.2018.1433033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300152PMC
March 2018

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

Hum Brain Mapp 2018 05 22;39(5):1929-1944. Epub 2018 Jan 22.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy.

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.
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http://dx.doi.org/10.1002/hbm.23972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866268PMC
May 2018

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness.

Hum Brain Mapp 2017 12 12;38(12):6068-6082. Epub 2017 Sep 12.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York.

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self-reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self-reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self-rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068-6082, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757871PMC
December 2017

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

Neuroimage Clin 2017 4;16:111-115. Epub 2017 Jul 4.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.

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.
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http://dx.doi.org/10.1016/j.nicl.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537392PMC
April 2018

Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.

Mov Disord 2017 04 10;32(4):560-568. Epub 2017 Feb 10.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Background: Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology.

Methods: Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes).

Results: Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus.

Conclusions: Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.26920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578762PMC
April 2017

Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study.

J Neurol 2016 Jun 19;263(6):1146-55. Epub 2016 Apr 19.

Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing-remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls (p values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score (ρ = -0.39, p = 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score (p values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics.
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http://dx.doi.org/10.1007/s00415-016-8118-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369414PMC
June 2016

The substrate of increased cortical FA in MS: A 7T post-mortem MRI and histopathology study.

Mult Scler 2016 12 4;22(14):1804-1811. Epub 2016 Mar 4.

Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.

Background: Using diffusion tensor imaging (DTI), it was previously found that demyelinated gray matter (GM) lesions have increased fractional anisotropy (FA) when compared to normal-appearing gray matter (NAGM) in multiple sclerosis (MS). The biological substrate underlying this FA change is so far unclear; both neurodegenerative changes and microglial activation have been proposed as causal contributors.

Objective: To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions.

Methods: We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry.

Results: Overall, there were few activated microglia/macrophages, and no difference between GM lesions and NAGM was observed. However, cell density was increased in GM lesions compared to NAGM (309.67 ± standard deviation (SD) 124.44 vs 249.95 ± SD 56.75, p = 0.002).

Conclusion: FA increase was not due to lesional and non-lesional differences in microglia activation and/or proliferation. We found an increase in general cellular density without a notable difference in cellular size, that is, tissue compaction, as a possible alternative explanation.
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http://dx.doi.org/10.1177/1352458516635290DOI Listing
December 2016

Brain intra- and extracellular sodium concentration in multiple sclerosis: a 7 T MRI study.

Brain 2016 Mar 20;139(Pt 3):795-806. Epub 2016 Jan 20.

1 Department of Neurology, Icahn School of Medicine, Mount Sinai, New York, USA 3 Department of Radiology, Icahn School of Medicine, Mount Sinai, New York, USA 6 Department of Neuroscience, Icahn School of Medicine, Mount Sinai, New York, USA 7 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.

Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P < 0.05 and P < 0.01), and intracellular sodium concentration (both P < 0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P = 0.62 and P < 0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P < 0.05 family-wise error corrected for total sodium concentration, P < 0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T2-weighted and T1-weighted lesion volumes (0.05 < P < 0.01) and with Expanded Disability Status Scale (P < 0.05). Thus, suggesting that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect neuro-axonal metabolic dysfunction.
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http://dx.doi.org/10.1093/brain/awv386DOI Listing
March 2016

Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal-appearing gray matter in multiple sclerosis.

Mult Scler 2016 09 16;22(10):1306-14. Epub 2015 Dec 16.

Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.

Background: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated.

Objective: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength.

Methods: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM.

Results: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM.

Conclusion: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects.
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http://dx.doi.org/10.1177/1352458515620499DOI Listing
September 2016

Sodium MRI of multiple sclerosis.

NMR Biomed 2016 Feb 6;29(2):153-61. Epub 2015 Apr 6.

Department of Neurology, Icahn School of Medicine, Mount Sinai, New York, USA.

Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young adults. The mechanisms underlying neurodegeneration and disease progression are poorly understood, in part as a result of the lack of non-invasive methods to measure and monitor neurodegeneration in vivo. Sodium MRI is a topic of increasing interest in MS research as it allows the metabolic characterization of brain tissue in vivo, and integration with the structural information provided by (1)H MRI, helping in the exploration of pathogenetic mechanisms and possibly offering insights into disease progression and monitoring of treatment outcomes. We present an up-to-date review of the sodium MRI application in MS organized into four main sections: (i) biological and pathogenetic role of sodium; (ii) brief overview of sodium imaging techniques; (iii) results of sodium MRI application in clinical studies; and (iv) future perspectives.
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http://dx.doi.org/10.1002/nbm.3289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771413PMC
February 2016

Functional connectivity in the resting-state motor networks influences the kinematic processes during motor sequence learning.

Eur J Neurosci 2015 Jan 18;41(2):243-53. Epub 2014 Oct 18.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy.

Neuroimaging studies support the involvement of the cerebello-cortical and striato-cortical motor loops in motor sequence learning. Here, we investigated whether the gain of motor sequence learning could depend on a-priori resting-state functional connectivity (rsFC) between motor areas and structures belonging to these circuits. Fourteen healthy subjects underwent a resting-state functional magnetic resonance imaging session. Afterward, they were asked to reproduce a verbally-learned sequence of finger opposition movements as fast and as accurately as possible. All subjects increased their movement rate with practice, by reducing the touch duration and/or intertapping interval. The rsFC analysis showed that, at rest, the left and right primary motor cortex (M1) and left and right supplementary motor area (SMA) were mainly connected with other motor areas. The covariate analysis taking into account the different kinematic parameters indicated that the subjects achieving greater movement rate increase were those showing stronger rsFC of the left M1 and SMA with the right lobule VIII of the cerebellum. Notably, the subjects with greater intertapping interval reduction showed stronger rsFC of the left M1 and SMA with the association nuclei of the thalamus. Conversely, the regression analysis with the right M1 and SMA seeds showed only a few significant clusters for the different covariates not located in the cerebellum and thalamus. No common clusters were found between the right M1 and SMA. All of these findings indicated important functional connections at rest of those neural circuits responsible for motor learning improvement, involving the motor areas related to the hemisphere directly controlling the finger movements, the thalamus and cerebellum.
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http://dx.doi.org/10.1111/ejn.12755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396877PMC
January 2015

Noninvasive quantification of intracellular sodium in human brain using ultrahigh-field MRI.

NMR Biomed 2013 Jan 20;26(1):9-19. Epub 2012 Jun 20.

Department of Radiology, Mount Sinai School of Medicine, New York, NY 10029, USA.

In vivo sodium magnetic resonance imaging (MRI) measures tissue sodium content in living human brain but current methods do not allow noninvasive quantitative assessment of intracellular sodium concentration (ISC) - the most useful marker of tissue viability. In this study, we report the first noninvasive quantitative in vivo measurement of ISC and intracellular sodium volume fraction (ISVF) in healthy human brain, made possible by measuring tissue sodium concentration (TSC) and intracellular sodium molar fraction (ISMF) at ultra-high field MRI. The method uses single-quantum (SQ) and triple-quantum filtered (TQF) imaging at 7 Tesla to separate intra- and extracellular sodium signals and provide quantification of ISMF, ISC and ISVF. This novel method allows noninvasive quantitative measurement of ISC and ISVF, opening many possibilities for structural and functional metabolic studies in healthy and diseased brains.
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http://dx.doi.org/10.1002/nbm.2813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691850PMC
January 2013

Exploiting sparsity to accelerate noncontrast MR angiography in the context of parallel imaging.

Magn Reson Med 2012 May 29;67(5):1391-400. Epub 2011 Aug 29.

Department of Radiology, New York University School of Medicine, New York, New York 10016, USA.

Noncontrast techniques for peripheral MR angiography are receiving renewed interest because of safety concerns about the use of gadolinium in patients with renal insufficiency. One class of techniques involves subtraction of dark-blood images acquired during fast systolic flow from bright-blood images obtained during slow diastolic flow. The goal of this work was to determine whether the inherent sparsity of the difference images could be exploited to achieve greater acceleration without loss of image quality in the context of generalized autocalibrating partially parallel acquisition (GRAPPA). It is shown that noise amplification at high acceleration factors can be reduced by performing subtraction on the raw data, before calculation of the GRAPPA weights, rather than on the final magnitude images. Use of the difference data to calculate the GRAPPA weights decreases the geometry factor (g-factor), because the difference data represent a sparse image set. This demonstrates an inherent property of GRAPPA and does not require the use of compressed sensing. Application of this approach to highly accelerated data from healthy volunteers resulted in similar depiction of large arteries to that obtained with low acceleration and standard reconstruction. However, visualization of very small vessels and arterial branches was compromised.
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http://dx.doi.org/10.1002/mrm.23132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291797PMC
May 2012

Progressive multiple sclerosis and gray matter pathology: an MRI perspective.

Mt Sinai J Med 2011 Mar-Apr;78(2):258-67

Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.

The evidence suggesting a role of extensive cortical demyelization and atrophy in progressive multiple sclerosis is rapidly increasing. Although conventional magnetic resonance imaging has had a huge impact on multiple sclerosis by enabling an earlier diagnosis, and by providing surrogate markers for monitoring disease response to anti-inflammatory/immunomodulatory treatments, it is limited by the low pathological specificity and the low sensitivity to both diffuse damage in normal-appearing white matter and focal and diffuse damage in gray matter. Advanced magnetic resonance imaging techniques can partially overcome these limitations by providing markers more specific to the underlying pathologic substrates and more sensitive to the structural and functional "occult" brain tissue damage in patients with multiple sclerosis. This review describes brain and spinal cord imaging studies of multiple sclerosis with particular emphasis on gray matter imaging in both secondary progressive and primary progressive multiple sclerosis, discusses the clinical implications of gray matter damage, and outlines current magnetic resonance imaging developments at high and ultrahigh magnetic field strength.
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http://dx.doi.org/10.1002/msj.20247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079372PMC
July 2011