Thalamic Gray Matter Research Articles

Structural MRI findings in the brain related to pain distribution in chronic overlapping pain conditions: An explorative case-control study in females with fibromyalgia, temporomandibular disorder-related chronic pain and pain-free controls.

Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution. To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain-free controls (CON) using structural and diffusion MRI. A case-control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1-weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity. Patients with FM had smaller volume in the right thalamus than patients with TMD (p = .020) and CON (p = .030). The right thalamus volume was negatively correlated to pain intensity (r = -0.37, p = .022) and pain-related disability (r = -0.45, p = .004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p = .005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = - 0.48, p = .002). This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system.

Demyelination in Patients with POST-COVID Depression.

Background: Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression (PCD) using the recently proposed MRI method, macromolecular proton fraction (MPF) mapping. Methods: The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, and 2 severe) at 13.5 ± 10.0 months post-recovery, with matched controls without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n = 38) included participants with neurological COVID-19 complications, excluding clinical depression. Results: Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination, but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of Hamilton scores, PCD presence, and severity. The number of post-COVID symptoms was a significant predictor of PCD presence, while the number of acute symptoms was a significant predictor of PCD severity. Conclusions: This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome.

The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics. Standardized 3T MRIs including 3D isotropicT1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired datawere analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord. The study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of -4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event,a greater reduction in medulla-upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443). The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures.

Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.

A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach. For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures. We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found. CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

Association between sleep spindles and thalamic grey matter volume following moderate to severe traumatic brain injury

Association between sleep spindles and thalamic grey matter volume following moderate to severe traumatic brain injury

Abstract TMP93: Severe Non-Contrast CT Hypodensity Modifies EVT Treatment Effect and is Associated With Worse Outcomes Independent of Ischemic Core Volume: A Secondary Analysis of the SELECT2 Trial

Introduction: Endovascular thrombectomy (EVT) reduces disability in patients with large ischemic core stroke. Increasing core volume is prognostic but does not modify treatment effect. CT hypodensity can vary within an area of core. We assessed the relationship between the severity of CT core hypodensity and clinical outcome in the SELECT2 trial. Methods: Non-contrast CT ischemic core was drawn manually by two blinded investigators with consensus review by a third investigator. An absolute Hounsfield unit (HU) threshold for severe hypodensity was set at the lower 99% confidence interval [CI] for normal contralateral thalamic grey matter. Outcomes assessed included ordinal mRS, functional independence (mRS 0-2), independent ambulation (mRS 0-3), and mortality at 90 days. The association between the volume of severe hypodensity and outcome was adjusted for age, baseline NIHSS, and total baseline core volume, via logistic and proportional odds models with treatment*hypodensity interaction. Results: Of 317 assessable patients, the median hypodensity of ischemic core was 31HU (IQR 28-33). Median density of normal thalamus was 38HU. The severe hypodensity threshold (lower 99% CI) was 26HU with median volume affected 14mL (IQR 5.6-29.2) or median 19% (IQR 9-35%) of the total hypodensity volume. The volume of core ≤26HU (per 1 mL increase) was associated with a 90-day mRS shift towards worse outcomes in EVT patients (n=161, adjusted common odds ratio, acOR 1.03, 95%CI 1.01-1.05) but not medical management ([MM], n=156, acOR 1.00, 95%CI 0.98-1.02, p-interaction 0.005); lower functional independence in EVT (aOR 0.96 95%CI 0.93-0.99) but not MM (aOR 1.02, 95%CI 0.99-1.06, p-interaction 0.004); lower independent ambulation in EVT (aOR 0.97, 95%CI 0.94-0.99) but not MM (aOR 1.01, 95%CI 0.98-1.04, p-interaction 0.002) and higher mortality in EVT (aOR 1.03, 95%CI 1.01-1.05) but not MM (aOR 1.00, 95%CI 0.98-1.02, p-interaction 0.02). Conclusion: In patients with large ischemic core, areas of significant CT hypodensity are associated with worse clinical outcomes after EVT but not MM. This is independent of total core volume and modifies the treatment effect of EVT. This may improve prognostic decision-making and drive developments in automated image processing.

The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN)

BackgroundWe aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach.ResultsSixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.ConclusionErenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.

Can exercise-based interventions reverse gray and white matter abnormalities in patients with chronic musculoskeletal pain? A systematic review.

Recent evidence has suggested that reversal of gray or white matter abnormalities could be a criterion of recovery in patients with chronic pain. To determine the effectiveness of exercise-based interventions in reversing gray and white matter abnormalities in patients with chronic musculoskeletal pain. An electronic search was performed in the MEDLINE (Via PubMed), EMBASE, Web of Science, LILACS, SPORTDiscus, CINAHL, PEDro, and CENTRAL databases for articles published up to November 2022. Randomized clinical trials (RCTs) including patients with chronic musculoskeletal pain, which assessed the change in gray and white matter abnormalities after exercise-based interventions were selected. The risk of bias was assessed using the Risk of Bias II tool. Four RCTs were included (n= 386). Three studies showed reversal of abnormalities with exercise-based interventions compared to control groups. The reversal was observed in the gray matter volume in the medial orbital prefrontal cortex and in the supplementary motor area of patients with osteoarthritis, in the hippocampus, insula, amygdala and thalamus in fibromyalgia patients. Furthermore, in patients with chronic spinal pain, reversal was observed in the gray matter thickness of the frontal middle caudal cortex and in the caudate, putamen and thalamus gray matter volume. There is insufficient evidence to determine the effectiveness of exercise-based interventions for reversing gray and white matter abnormalities in patients with chronic pain. Further studies are still needed in this field.

Increased thalamic gray matter volume induced by repetitive transcranial magnetic stimulation treatment in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in improving depressive symptoms in MDD patients, but the intrinsic mechanism is still unclear. In this study, we investigated the influence of rTMS on brain gray matter volume for alleviating depressive symptoms in MDD patients using structural magnetic resonance imaging (sMRI) data. Patients with first episode, unmedicated patients with MDD (n = 26), and healthy controls (n = 31) were selected for this study. Depressive symptoms were assessed before and after treatment by using the HAMD-17 score. High-frequency rTMS treatment was conducted in patients with MDD over 15 days. The rTMS treatment target is located at the F3 point of the left dorsolateral prefrontal cortex. Structural magnetic resonance imaging (sMRI) data were collected before and after treatment to compare the changes in brain gray matter volume. Before treatment, patients with MDD had significantly reduced gray matter volumes in the right fusiform gyrus, left and right inferior frontal gyrus (triangular part), left inferior frontal gyrus (orbital part), left parahippocampal gyrus, left thalamus, right precuneus, right calcarine fissure, and right median cingulate gyrus compared with healthy controls (P < 0.05). After rTMS treatment, significant growth in gray matter volume of the bilateral thalamus was observed in depressed patients (P < 0.05). Bilateral thalamic gray matter volumes were enlarged in the thalamus of MDD patients after rTMS treatment and may be the underlying neural mechanism for the treatment of rTMS on depression.

Effectiveness of ocrelizumab on clinical and MRI outcome measures in multiple sclerosis across black and white cohorts: A single-center retrospective study.

To examine differences in the therapeutic response to ocrelizumab in multiple sclerosis (MS) patients who self-identified as either White or Black, assessed longitudinally by expanded disability status scale (EDSS) progression and MRI brain volume loss. MS subjects treated with ocrelizumab were retrospectively identified. Clinical data were available for 229 subjects (White 146; Black 83) and MRI data from for 48 subjects (White 31; Black 17). Outcome measures were changes in the EDSS and brain volume over time. EDSS were analyzed as raw scores, ambulatory (EDSS <5.0) vs. ambulatory with assistance (5.5 ≤ EDSS ≤ 6.5) status, and EDSS severity (< 3.0, 3.0-5.0, and > 5.5 ≤ 6.5). General linear mixed model was used for statistical analysis. FreeSurfer was used for volumetric analysis. The Black cohort had overrepresentation of females (78% vs. 62%, p=0.013), lower age (median, 45 (IQR 39-51) vs. 49 (38-58), p=0.08), lower Vitamin D levels (33 (21-45) vs. 40 (29-52), p=0.002), and higher EDSS (4 (2-6) vs. 2.5 (1-6), p=0.019). There was no progression of EDSS scores over the 2-year observation period. The covariates with significant influence on the baseline EDSS scores were older age, race, longer disease duration, prior MS treatment, and lower vitamin D levels. No differences were observed between the racial groups over time in the cortical, thalamic, caudate, putamen, and brainstem gray matter volumes nor in the cortical thickness or total lesion volume. In this real-world clinical and radiological study, ocrelizumab treatment was highly effective in stabilizing clinical and MRI measures of disease progression in Blacks and Whites, despite higher baseline disability in the Black cohort.

Same Sexual Orientation as a Potential Risk Factor for Severe Mental Illness

Considered as a minority, the LGBTQ (Lesbian, Gay, Bisexual, Transgender, and Queer) community including homosexual males is more prone to mental distress. Studies on prevalence stated that sexual orientation minorities are susceptible to inept mental health outcomes, and the rate of anxiety disorders, schizophrenia, and psychotic illness is twice higher in gay and bisexual men rather than in heterosexuals. Along with that, several investigations found similarity between structural features in the brain of schizophrenic patients and homosexual males. This study intends to analyze the male homosexuality as a potential risk factor for schizophrenia. According to MRI (magnetic resonance imaging) findings, brain structures similarity is found between schizophrenic patients and homosexual men specifically on the thalamic grey matter volume and cortical thickness of the brain. Both schizophrenic patients and homosexual males exhibit reduced grey matter volume in the thalamus region, meanwhile schizophrenic patients have lower grey matter volume in the left putamen and homosexual males showed higher left putamen grey matter volume compared to heterosexual individuals. The cortex of schizophrenic patients is thinner in left orbitofrontal, right parahippocampal, and superior temporal area, resembling to thinner cortex in the right lateral orbitofrontal regions and regions in the visual cortex of homosexual males. Based on the reviewed journals, male homosexuality can be a potential risk factor for schizophrenia considering their correlation in neurodevelopmental deviations. Nevertheless, further investigations are needed regarding other factors and pathways causing such structural brain changes in both conditions. Keywords: grey matter, homosexual, neurodevelopmental, schizophrenia

Aging of the brain in bipolar disorder: Illness- and onset-related effects in cortical thickness and subcortical gray matter volume

BackgroundOlder adults with bipolar disorder (BD) have received little study, although they often have severe symptoms, treatment resistance and high suicide risk. Furthermore, a subset develops cognitive dysfunction for unknown reasons. MethodsHere, cortical thickness and subcortical gray matter volume were compared across individuals ages 40-79y: 103 with BD (“later-onset” at ages ≥25y, n = 21; “early-onset” < 25y, n = 82) and healthy controls (HCs, n = 98). ResultsOverall, those with BD showed lower prefrontal, cingulate, sensorimotor, parahippocampal, insula, temporal, parietal, and occipital cortical thickness (Cohen's d: 0.4 to 0.8) and hippocampal, amygdalar, thalamic, and striatal gray matter volume (d: 0.6 to 0.8). Later-onset BD showed negative relationships between age and parahippocampal, insular, temporal, parietal, and occipital cortical thickness, and hippocampal, thalamic and striatal volume (r: −0.7 to −0.4). Suicide attempt history was associated with lower dorsolateral prefrontal cortical thickness (d = 0.5). LimitationsThe study used a cross-sectional design and the sample of those with a later-onset of BD was relatively modest. ConclusionsResults support widespread gray matter decreases in older adults with BD, and also suggest a separable later-onset phenotype characterized by age-related gray matter reductions in regions subserving cognitive, emotional and perceptual processes. Moreover, the results are the first to demonstrate structural brain differences associated with a history of suicide attempts in older adults with BD.

Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

Thalamic atrophy, duration of illness, and years of education are the best predictors of cognitive impairment in multiple sclerosis

Background Cognitive impairment (CI) is common in multiple sclerosis. We assessed the relationship between CI and demographic, motor disability, and volumetric brain atrophy in relapsing remitting multiple sclerosis (RRMS). Methods In all, 43 RRMS patients and 40 age- sex-, and education-matched normal volunteers were enrolled. Assessments included: demographic, Expanded Disability Status Scale (EDSS); Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS); and brain volumetric assessment. Results The mean age of onset of RRMS patients was 25.72 y and the mean number of attacks was 3.30 ± 2.33/year. The total brain volume, cerebral, and cerebellar hemispheres, brainstem as well as thalamic and hippocampal gray matter were significantly reduced in RRMS patients compared with controls. CI was detected in 41.9% of patients. Patients with CI had fewer years of education (P = .001), a higher number of attacks (P = .002), worse EDSS scores (P = .030); reduced gray matter volume, particularly of the thalamus, and hippocampus compared with patients without CI. There were significant negative correlations between CI with duration of illness, number of attacks, time elapsed between onset and diagnosis, and EDSS. Thalamic volume showed strong positive correlations with CI (P < .0001). The best predictors of CI were thalamic atrophy, duration of illness, and years of education (P = .001, .010, and .035 respectively). Conclusion We confirmed the presence of gray matter atrophy of the brain in RRMS patients. Volumetric magnetic resonance imaging measures of thalamus, duration of illness, and years of education could be useful biomarkers of CI in RRMS.

Coping With Anxiety: Brain Structural Correlates of Vigilance and Cognitive Avoidance.

BackgroundIndividuals differ in their dispositional coping behavior when they are confronted with anxiety-provoking situations. Cognitive avoidance is characterized by a withdrawal from threatening information, whereas vigilance denotes the intensive search for threat-related information. Functional neuroimaging studies indicate alterations in brain responsivity to emotional stimuli as a function of cognitive avoidant and vigilant coping, but findings are partially discrepant. Studies on structural correlates of coping styles are scarce.Materials and MethodsBy using structural magnetic resonance imaging, the present study examined the relationship between brain gray matter volume and coping strategies in 114 healthy individuals. Individual differences in vigilance and cognitive avoidance were measured by the Mainz Coping Inventory.ResultsExploratory whole-brain analyses were conducted. Cognitive avoidant coping significantly predicted reduced gray matter volume in the bilateral thalamus, whereas vigilant coping was associated with volumetric increases in the bilateral thalamus. These relationships remained significant when controlling for a potential influence of age, sex, depressive symptoms, and trait anxiety.DiscussionOur findings indicate that dispositional strategies to deal with anxiety-provoking situations are related to volumetric alterations in the thalamus, a brain structure that has been implicated in the mediation of attentional processes and alertness, and the anticipation of harm. The dispositional tendency to monitor the environment for potential threats (i.e., vigilance), appears to be associated with volumetric increases in the thalamus, whereas the dispositional inclination to divert one’s attention away from distressing stimuli (i.e., cognitive avoidance) seems to go along with reductions in thalamic gray matter density.

No Dopamine Agonist Modulation of Brain [18F]FEOBV Binding in Parkinson's Disease.

The [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) ligand targets the vesicular acetylcholine transporter. Recent [18F]FEOBV PET rodent studies suggest that regional brain [18F]FEOBV binding may be modulated by dopamine D2-like receptor agents. We examined associations of regional brain [18F]FEOBV PET binding in Parkinson's disease (PD) subjects without versus with dopamine D2-like receptor agonist drug treatment. PD subjects (n = 108; 84 males, 24 females; mean age 68.0 ± 7.6 [SD] years), mean disease duration of 6.0 ± 4.0 years, and mean Movement Disorder Society-revised Unified PD Rating Scale III 35.5 ± 14.2 completed [18F]FEOBV brain PET imaging. Thirty-eight subjects were taking dopamine D2-like agonists. Vesicular monoamine transporter type 2 [11C]dihydrotetrabenazine (DTBZ) PET was available in a subset of 54 patients. Subjects on dopamine D2-like agonists were younger, had a longer duration of disease, and were taking a higher levodopa equivalent dose (LED) compared to subjects not taking dopamine agonists. A group comparison between subjects with versus without dopamine D2-like agonist use did not yield significant differences in cortical, striatal, thalamic, or cerebellar gray matter [18F]FEOBV binding. Confounder analysis using age, duration of disease, LED, and striatal [11C]DTBZ binding also failed to show significant regional [18F]FEOBV binding differences between these two groups. Chronic D2-like dopamine agonist use in PD subjects is not associated with significant alterations of regional brain [18F]FEOBV binding.

Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson’s disease

ObjectiveVisual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical...

Altered thalamic gray matter volume in firefighters with heavy alcohol use

BackgroundAlcohol, a known addictive substance, affects the structural properties of the brain. In this study, we explored associations between alcohol use and gray matter properties among firefighters, who are often exposed to significant occupational stress. MethodsGray matter volume (GMV) was evaluated using voxel-based morphometry in 287 male firefighters (mean age: 48.8 ± 7.7 years). Firefighters were classified into 32 never-drinkers, 162 non-heavy alcohol users, and 93 heavy alcohol users according to their alcohol consumption. GMV was compared between groups, and the correlations between GMV and alcohol use were investigated. A voxel-wise height threshold of p < 0.001 (uncorrected) was used, with small volume correction applied on cluster level. ResultsHeavy alcohol users had lower GMV in the bilateral thalamus than non-heavy alcohol users or never-drinkers. Heavy alcohol users also showed lower GMV in the left insula, compared to other groups. The higher the alcohol consumption among firefighters, the lower the GMV of the right thalamus. ConclusionsThe results of this study show that heavy alcohol use has an association with lower GMV in several core regions, including the thalamus. When considering the impact of these brain regions on cognitive and behavioral control, our findings suggest a need for concern about heavy alcohol use among firefighters.

Association of Disease Severity and Socioeconomic Status in Black and White Americans With Multiple Sclerosis

To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BAs) and White Americans (WAs) and to evaluate the role of socioeconomic status. We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics, including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit zip codes. Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or to be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs mild disability, 95% confidence interval [CI] 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, 95% CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96), and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BAs. We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors; developing optimal treatment strategies among BAs with MS is warranted.

Machine learning classifier to identify clinical and radiological features relevant to disability progression in multiple sclerosis

ObjectivesTo evaluate the accuracy of a data-driven approach, such as machine learning classification, in predicting disability progression in MS.MethodsWe analyzed structural brain images of 163 subjects diagnosed with MS acquired at two different sites. Participants were followed up for 2–6 years, with disability progression defined according to the expanded disability status scale (EDSS) increment at follow-up. T2-weighted lesion load (T2LL), thalamic and cerebellar gray matter (GM) volumes, fractional anisotropy of the normal appearing white matter were calculated at baseline and included in supervised machine learning classifiers. Age, sex, phenotype, EDSS at baseline, therapy and time to follow-up period were also included. Classes were labeled as stable or progressed disability. Participants were randomly chosen from both sites to build a sample including 50% patients showing disability progression and 50% patients being stable. One-thousand machine learning classifiers were applied to the resulting sample, and after testing for overfitting, classifier confusion matrix, relative metrics and feature importance were evaluated.ResultsAt follow-up, 36% of participants showed disability progression. The classifier with the highest resulting metrics had accuracy of 0.79, area under the true positive versus false positive rates curve of 0.81, sensitivity of 0.90 and specificity of 0.71. T2LL, thalamic volume, disability at baseline and administered therapy were identified as important features in predicting disability progression. Classifiers built on radiological features had higher accuracy than those built on clinical features.ConclusionsDisability progression in MS may be predicted via machine learning classifiers, mostly evaluating neuroradiological features.