Brain Gray Matter Research Articles

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

Postoperative delirium is associated with grey matter brain volume loss.

Delirium is associated with long-term cognitive dysfunction and with increased brain atrophy. However, it is unclear whether these problems result from or predisposes to delirium. We aimed to investigate preoperative to postoperative brain changes, as well as the role of delirium in these changes over time. We investigated the effects of surgery and postoperative delirium with brain MRIs made before and 3 months after major elective surgery in 299 elderly patients, and an MRI with a 3 months follow-up MRI in 48 non-surgical control participants. To study the effects of surgery and delirium, we compared brain volumes, white matter hyperintensities and brain infarcts between baseline and follow-up MRIs, using multiple regression analyses adjusting for possible confounders. Within the patients group, 37 persons (12%) developed postoperative delirium. Surgical patients showed a greater decrease in grey matter volume than non-surgical control participants [linear regression: B (95% confidence interval) = -0.65% of intracranial volume (-1.01 to -0.29, P < 0.005)]. Within the surgery group, delirium was associated with a greater decrease in grey matter volume [B (95% confidence interval): -0.44% of intracranial volume (-0.82 to -0.06, P = 0.02)]. Furthermore, within the patients, delirium was associated with a non-significantly increased risk of a new postoperative brain infarct [logistic regression: odds ratio (95% confidence interval): 2.8 (0.7-11.1), P = 0.14]. Our study was the first to investigate the association between delirium and preoperative to postoperative brain volume changes, suggesting that delirium is associated with increased progression of grey matter volume loss.

Associations Between Cognition and Serotonin 1B Receptor Availability in Healthy Volunteers: A [11C]AZ10419369 Positron Emission Tomography Study.

The serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains. Forty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand [11C]AZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system. Replication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability. Higher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.

Traumatic stress load and stressor reactivity score associated with accelerated gray matter maturation in youths indexed by normative models.

Understanding how traumatic stress affects typical brain development during adolescence is critical to elucidate underlying mechanisms related to both maladaptive functioning and resilience after traumatic exposures. The current study aimed to map deviations from normative ranges of brain gray matter for youths with traumatic exposures. For each cortical and subcortical gray matter region, normative percentiles of variations were established using structural MRI from typically developing youths without any traumatic exposure (n = 245; age range = 8-23) from the Philadelphia Neurodevelopmental Cohort (PNC). The remaining PNC participants with neuroimaging data (n = 1129) were classified as either within the normative range (5-95%), delayed (>95%) or accelerated (<5%) maturational ranges for each region using the normative model. An averaged quantile regression index was calculated across all regions. Mediation models revealed that high traumatic stress load was positively associated with poorer cognitive functioning and greater psychopathology, and these associations were mediated by accelerated gray matter maturation. Furthermore, higher stressor reactivity scores, which represent a less resilient response under traumatic stress, were positively correlated with greater acceleration of gray matter maturation (r = 0.224, 95% CI = [0.17, 0.28], p < 0.001), suggesting that more accelerated maturation was linked to greater stressor response regardless of traumatic stress load. We conclude that traumatic stress is a source of deviation from normative brain development associated with poorer cognitive functioning and more psychopathology in the long run.

Is There Reduced Hemodynamic Brain Activation in Multiple Sclerosis Even with Undisturbed Cognition?

Cognitive impairments related to changes in deep gray matter and other brain regions occur in up to 70% of people with multiple sclerosis. But do such brain changes also occur in patients without significant cognitive impairment? Eighteen participants with relapsing-remitting multiple sclerosis (RRMS) and fifteen healthy controls participated in this study. Cognitive status, depression, and fatigue were assessed using the Multiple Sclerosis Inventory of Cognition (MUSIC), Beck's Depression Inventory (BDI-II), and the Fatigue Severity Scale (FSS). fMRI was recorded while a participant performed the modified attention network test (ANT). The effects of ANT executive attention network on hemodynamic activation of a priori defined regions of interest, including the hippocampus, anterior cingulate cortex (ACC), thalamus, caudate nucleus, pallidum, and putamen were studied. The individual lesion load was estimated. For fMRI data analysis a general linear model with randomization statistics including threshold-free cluster enhancement as implemented in the FSL software was used. Participants with RRMS showed reduced activation of the executive attention network in the hippocampus, pallidum, and ACC. The thalamus was involved in both group activations but did not differ between groups. In summary, functional changes in the brain can also be demonstrated in RRMS patients without cognitive deficits. The affected brain regions can best be assigned to the attention network for executive control. This association could likely serve as a biological indicator of susceptibility to imminent cognitive impairment in MS.

The Effect of Freezing and Thawing on Complex Permittivity of Bovine Tissues.

The aim of this study was to investigate how the freezing and thawing of biological tissues affect their complex permittivity in the microwave frequency range from 0.5 MHz to 18 GHz. We measured the complex permittivity of ex vivo bovine tissues, including brain white and grey matter, liver, and muscle, using an open-ended coaxial probe. Bovine tissues were chosen for their availability and similarity to human tissue permittivity. The samples were measured at 25 °C, before they were frozen either in a commercial freezer below -18 °C or in liquid nitrogen, nominally at -196 °C. The measured permittivity before freezing was compared to the permittivity measured after freezing and thawing the tissues back to 25 °C. Statistical analysis of the results showed a statistically significant change in permittivity after freezing and thawing by both methods for all the measured tissues, at least in some parts of the measured frequency range. The largest difference was observed for the white matter, while the liver had the smallest percent change.

Linking early-life bilingualism and cognitive advantage in older adulthood

Previous studies have identified bilingualism as a protective factor against dementia. Here we aimed to test whether being bilingual at different life stages impacts cognition and brain structure in older adulthood. We included 746 participants from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Assessment of bilingualism at 3 life stages (early: 13–30, middle: 30–65 and late: over 65 years old) was determined with the Lifetime of Experiences Questionnaire. Individuals reporting bilingualism (i.e., daily use of L2) in the early life stage outperformed monolinguals on learning & memory, working-memory, executive functions and language. Bilingualism in middle life stage showed a significant advantage on learning & memory, while no effect of bilingualism in old life stage was identified. Brain gray matter volume was not associated with L2 use and did not differ between groups. However, stronger correlations between brain gray matter volume in selected brain regions and cognitive performance were found in bilingual participants in the early and middle life stages. Our results indicate that bilingualism in early life might provide a long-lasting protective effect on cognition and shape the brain to sustain cognitive performance in older adulthood.

Smoking is associated with lower brain volume and cognitive differences: A large population analysis based on the UK Biobank

The evidence about the association of smoking with both brain structure and cognitive functions remains inconsistent. Using structural magnetic resonance imaging from the UK Biobank (n = 33,293), we examined the relationships between smoking status, dosage, and abstinence with total and 166 regional brain gray matter volumes (GMV). The relationships between the smoking parameters with cognitive function, and whether this relationship was mediated by brain structure, were then investigated. Smoking was associated with lower total and regional GMV, with the extent depending on the frequency of smoking and on whether smoking had ceased: active regular smokers had the lowest GMV (Cohen's d = −0.362), and former light smokers had a slightly smaller GMV (Cohen's d = −0.060). The smaller GMV in smokers was most evident in the thalamus. Higher lifetime exposure (i.e., pack-years) was associated with lower total GMV (β = −311.84, p = 8.35 × 10−36). In those who ceased smoking, the duration of abstinence was associated with a larger total GMV (β = 139.57, p = 2.36 × 10−08). It was further found that reduced cognitive function was associated with smoker parameters and that the associations were partially mediated by brain structure. This is the largest scale investigation we know of smoking and brain structure, and these results are likely to be robust. The findings are of associations between brain structure and smoking, and in the future, it will be important to assess whether brain structure influences smoking status, or whether smoking influences brain structure, or both.

Decoding individual differences in expressing and suppressing anger from structural brain networks: A supervised machine learning approach

Anger can be broken down into different elements: a transitory state (state anger), a stable personality feature (trait anger), a tendency to express it (anger-out), or to suppress it (anger-in), and the ability to regulate it (anger control). These elements are characterized by individual differences that vary across a continuum. Among them, the abilities to express and suppress anger are of particular relevance as they determine outcomes and enable successful anger management in daily situations. The aim of this study was to demonstrate that anger suppression and expression can be decoded by patterns of grey matter of specific well-known brain networks. To this aim, a supervised machine learning technique, known as Kernel Ridge Regression, was used to predict anger expression and suppression scores of 212 healthy subjects from the grey matter concentration. Results show that individual differences in anger suppression were predicted by two grey matter patterns associated with the Default-Mode Network and the Salience Network. Additionally, individual differences in anger expression were predicted by a circuit mainly involving subcortical and fronto-temporal regions when considering whole brain grey matter features. These results expand previous findings regarding the neural bases of anger by showing that individual differences in specific anger-related components can be predicted by the grey matter features of specific networks.

Effects of Alzheimer’s Disease Risk Factors on Cerebrovascular Dynamics in Gray Matter

AbstractBackgroundCerebrovascular functional parameters such as cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and arterial transit time (ATT) may play an essential role in understanding the vascular contributions to dementia (VCID). We investigated the relationships between cerebrovascular functional parameters and AD risk factors, including APOE genotype, hypertension, and diabetes.MethodSixty‐five subjects (Table 1) enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort underwent MRI, including pseudo‐continuous ASL (PCASL). CVR maps were obtained under a hypercapnic challenge using a computer‐controlled gas blender. A multi‐TI PCASL sequence was also employed to obtain resting CBF and ATT. Separate linear regression models were tested with response variables of quantitative CBF, CVR and ATT in whole brain gray matter (GM) and AD‐prone GM regions including hippocampus, parahippocampal, entorhinal, inferior parietal lobule, precuneus, and cuneus, adjusted for covariates: age, sex, and years of education. To investigate the effects of a risk factor on the interrelated vascular dynamic parameters, a cerebrovascular composite was created with the implementation of the weighting factors, obtained from covariates adjusted logistic regression, for each AD risk group and mild cognitive impairment (MCI). The factor score p‐values were calculated from two‐sample t‐tests with the cerebrovascular composite.ResultIn both whole brain GM and AD‐prone GM regions, subjects with the risk factors generally had lower resting CBF, but differential relationship with CVR. Subjects with hypertension had significantly higher CVR, while APOE e4 carriers showed significantly lower CVR (Figure 1 and 2). From the cerebrovascular composite analysis, CVR showed higher weights in hypertension and APOE e4 carrier groups in both whole brain GM and AD‐prone GM regions (Table 2) although there still were fractions of linear weights of CBF or ATT, which were not negligible.ConclusionHypertension and APOE e4 carrier showed group differences of CVR in both whole brain GM and AD‐prone GM regions and the directions were opposite, implying their pathophysiological mechanisms may differ. As resting CBF and ATT showed lower weights in the composite than CVR, CVR may be a more sensitive brain perfusion parameter relating VCID.

Effects of Alzheimer’s Disease Risk Factors on Cerebrovascular Dynamics in Gray Matter

AbstractBackgroundCerebrovascular functional parameters such as cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and arterial transit time (ATT) may play an essential role in understanding the vascular contributions to dementia (VCID). We investigated the relationships between cerebrovascular functional parameters and AD risk factors, including APOE genotype, hypertension, and diabetes.MethodSixty‐five subjects (Table 1) enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort underwent MRI, including pseudo‐continuous ASL (PCASL). CVR maps were obtained under a hypercapnic challenge using a computer‐controlled gas blender. A multi‐TI PCASL sequence was also employed to obtain resting CBF and ATT. Separate linear regression models were tested with response variables of quantitative CBF, CVR and ATT in whole brain gray matter (GM) and AD‐prone GM regions including hippocampus, parahippocampal, entorhinal, inferior parietal lobule, precuneus, and cuneus, adjusted for covariates: age, sex, and years of education. To investigate the effects of a risk factor on the interrelated vascular dynamic parameters, a cerebrovascular composite was created with the implementation of the weighting factors, obtained from covariates adjusted logistic regression, for each AD risk group and mild cognitive impairment (MCI). The factor score p‐values were calculated from two‐sample t‐tests with the cerebrovascular composite.ResultIn both whole brain GM and AD‐prone GM regions, subjects with the risk factors generally had lower resting CBF, but differential relationship with CVR. Subjects with hypertension had significantly higher CVR, while APOE e4 carriers showed significantly lower CVR (Figure 1 and 2). From the cerebrovascular composite analysis, CVR showed higher weights in hypertension and APOE e4 carrier groups in both whole brain GM and AD‐prone GM regions (Table 2) although there still were fractions of linear weights of CBF or ATT, which were not negligible.ConclusionHypertension and APOE e4 carrier showed group differences of CVR in both whole brain GM and AD‐prone GM regions and the directions were opposite, implying their pathophysiological mechanisms may differ. As resting CBF and ATT showed lower weights in the composite than CVR, CVR may be a more sensitive brain perfusion parameter relating VCID.

Modifying effect of AD pathology in the association between CSF synaptic biomarkers and brain function and structure in preclinical Alzheimer

AbstractBackgroundPrevious studies have shown that synaptic biomarkers are increased in CSF in the preclinical stage of Alzheimer’s disease (AD). However, little is known about how CSF synaptic biomarkers associate with structural and functional brain measures in preclinical Alzheimer. The aim of this study was to test the association of CSF synaptic biomarkers with brain metabolism and structure in preclinical Alzheimer and explore whether these associations were modified by AD pathology.MethodWe studied 328 cognitively‐unimpaired individuals of the ALFA+ cohort. Participants underwent lumbar puncture, [18F]‐FDG PET scan and structural MRI. The following synaptic biomarkers were measured in CSF: neurogranin (NeuroToolKit [a panel of automated robust prototype immunoassays], Roche Diagnostics International Ltd), GAP‐43 (ELISA), SNAP‐25 and synaptotagmin‐1 (IP‐MS). We performed voxel‐wise analyses to test the association of each synaptic biomarker with brain metabolism and grey matter volume, using a threshold of p&lt;0.005 and a minimum cluster size of 100 voxels. Participants were categorized by AT groups (A+ if CSF Aβ42/40&lt;0.071 and T+ if CSF p‐tau&gt;24pg/ml) and interaction terms with each synaptic biomarker were evaluated.Result212 (64.6%) participants were A‐T‐, 91 (27.7%) were A+T‐ and 25 (7.6%) were A+T+. To focus the study on the AD continuum, A‐T+ participants (n=12) were excluded. When assessing all participants, positive associations between each CSF synaptic biomarkers and FDG PET uptake and grey matter volume were found in brain areas including the caudate, the insula, cingulate gyrus and inferior temporal and parietal gyrus (Fig 1A). AT status modified the associations with both FDG PET uptake and grey matter volume. Compared to A‐T‐, A+T+ participants showed a positive association of CSF neurogranin, GAP‐43 and synaptotagmin‐1 with FDG PET uptake in the precuneus. Conversely, CSF synaptic biomarkers were negatively associated with grey matter volume with progressive AD pathology (A‐T‐&gt;A+T‐&gt;A+T+) in several brain regions including the cingulate gyrus and middle and superior frontal gyrus (Fig 1B).ConclusionIn preclinical Alzheimer, CSF synaptic biomarkers show associations with functional and structural brain measures, which are modified by AD pathology. Progressive AD pathology is associated with increased brain metabolism and decreased grey matter volume in several AD‐related brain regions.

Impact of CSF pTau/Aβ42 ratio on brain structure and metabolism in middle‐aged cognitively unimpaired individuals

AbstractBackgroundThe cerebrospinal fluid (CSF) pTau/Aβ42 ratio has emerged as a promising biomarker to monitor the pathological progression of Alzheimer’s disease (AD), even at preclinical stages. To date, no studies have assessed the impact of this continuous biomarker on the brain structure and metabolism in cognitively unimpaired (CU) individuals.MethodWe included 243 CU participants from the ALFA study (mean age=61.68 years) who underwent a lumbar puncture, magnetic resonance imaging (MRI) and 18F‐Fluorodeoxyglucose (FDG) positron emission tomography (PET). CSF Aβ42 and pTau181 were measured with the Elecsys® immunoassay (Roche Diagnostics International Ltd). After image preprocessing, we applied a voxel‐wise linear regression to test the impact of CSF pTau/Aβ42 ratio, as well as its interaction with age, sex and APOE‐ε4, on both gray matter volume (GMv) and brain metabolism. The statistical significance threshold was set to p&lt;0.005, with a cluster extent correction of 100 voxels.ResultThere were no main effects of pTau/Aβ42 on either GMv or brain metabolism. However, a significant interaction with age indicated that for older individuals, a higher pTau/Aβ42 was associated with reduced GMv in the middle cingulum, the middle and superior frontal gyrus, and the angular gyrus (Fig. 1a). An interaction with sex indicated that for females, a higher pTau/Aβ42 was associated with reduced GMv in the precuneus, superior frontal and fusiform gyrus (Fig. 1b). For FDG, we found a significant interaction with sex indicating that females exhibited a metabolism reduction with increasing levels of pTau/Aβ42, in the hippocampus and anterior cingulum (Fig. 1c). Finally, an interaction with APOE‐ε4 indicated that ε4‐carriers showed lower metabolism in the bilateral striatum, as a function of increasing pTau/Aβ42 ratio (Fig.1 d).ConclusionIn CU individuals, the impact of the progression of AD pathophysiology as indicated by a higher CSF pTau/Aβ42 ratio, on both brain structure and metabolism is modulated by AD risk factors. These data suggest that each of these risk factors confers a higher vulnerability to the progression of AD pathology in asymptomatic individuals, as manifested by an early impact on brain structure and metabolism in brain areas which are known to be affected in clinical AD stages.

Self‐reported sleep quality interacts with Alzheimer’s disease biomarkers on brain structure and metabolism in cognitively unimpaired adults

AbstractBackgroundPoor sleep quality has been associated with a greater burden of AD pathology and altered brain structure in cognitively unimpaired (CU) individuals. However, there is a lack of studies analysing associations between sleep quality and brain structure and function, while taking into account AD pathology. We aimed to test associations of self‐reported sleep quality with grey matter volume (GMv) and brain glucose metabolism in middle‐aged CU and sought interactions with biomarkers of AD pathology.MethodThis study included 340 CU adults from the ALFA+ cohort (Table 1). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) questionnaire. We used Statistical Parametric Mapping software to process T1‐weighted MRI and [18F]fluorodeoxyglucose (FDG) PET scans, and analyse voxel‐wise associations with sleep quality. We created separate general linear models with GMv and FDG metabolism as dependent variables, and PSQI total score, age, sex, APOE‐ε4 status, education level and sleep medication as predictors. GMv analyses were additionally corrected for total intracranial volume. In additional models, CSF Aβ42/40 and phosphorylated tau (p‐tau181) ‐ were entered as covariates. We also tested the interaction between PSQI and AD biomarker status, (A+: Aβ42/40&lt;0.071, T+: p‐tau181&gt;24 pg/mL). Statistical significance was set at p&lt;0.005 uncorrected for multiple comparisons, with a cluster‐level threshold of 50 voxels.ResultHigher PSQI scores, indicating poorer sleep quality, were significantly associated with lower GMv in the left occipital fusiform gyrus and right middle orbitofrontal gyrus, and with lower brain glucose metabolism in the right temporal pole and parahippocampal gyrus (Figure 1.). Interaction analyses showed poorer sleep quality is associated with higher GMv in bilateral supramarginal gyrus in A+T‐ vs A‐T‐, and with higher glucose metabolism in bilateral thalamus in A+T+ vs A‐T‐ individuals (Figure 2).ConclusionPoorer sleep quality is associated with lower GMv and glucose metabolism in CU individuals, involving AD‐vulnerable regions. Sleep quality interacted with altered AD biomarkers to determine GMv and glucose metabolism in brain areas in which they are commonly found to be increased in preclinical AD stages. Altogether, our findings support sleep quality as a relevant factor early in the AD continuum.

Toward a statistical foundation for brain signatures of behavioral outcome

AbstractBackgroundThe “brain signature of cognition” concept has garnered interest as a data‐driven, exploratory approach to better understand key brain regions involved in specific cognitive functions, with the potential to maximally characterize brain substrates of clinical outcomes. However, to be a robust brain phenotype, the signature approach requires a statistical foundation showing that model performance replicates across a variety of cohorts. Here, we outline a procedure that provides this foundation for a signature models of episodic memory and extend this to a measure of functional everyday memory.MethodUniversity of California, Davis (UCD) and ADNI provided imaging and memory data. For cognitive and ECog memory, we derived regional brain gray matter (GM) cortical thickness (CT) measures, testing for replicability (Fig. 1). Signature model generation used two steps in each cohort: 1) Randomly select 40 discovery subsets of size N = 400. In each subset, use voxelwise regression to compute the CT signature regions for outcome at three t‐values of association. 2) Compile frequency maps of region selection across all 40 discovery sets and designate regions with selection frequency &gt;70% as “consensus” signature masks for each cohort. Model validation used regressions of outcomes on consensus masks: 1) Compare adjusted R2 fits of both consensus signature models in 40 discovery sets in each cohort (thus, symmetrically compare same and oppositely generated models). 2) In each full cohort, compare signature model fits with competing models.ResultSpatial replications produced strongly convergent consensus signature regions derived from UCD and ADNI (Fig. 2). Consensus model fits were highly correlated in 40 random subsets of each cohort (Fig. 3 top) indicating high replicability, with tight (∼80%) ratios of within/outside cohort model fits (Fig. 3 bottom), indicating low bias. In comparisons over each full cohort, signature models outperformed other models with one exception (Fig. 4).ConclusionMultiple random model generations, followed by consensus selection of regional brain substrates, produced signature models that both consistently replicated model fits to memory and outperformed other commonly used measures. Results support consensus signature models as robust biomarkers of cognition and everyday function across imaging cohorts with differing demographic composition (see Table).

Brain grey and white matter structural associations with future suicidal ideation and behaviors in adolescent and young adult females with mood disorders.

To reduce suicide in females with mood disorders, it is critical to understand brain substrates underlying their vulnerability to future suicidal ideation and behaviors (SIBs) in adolescence and young adulthood. In an international collaboration, grey and white matter structure was investigated in adolescent and young adult females with future suicidal behaviors (fSB) and ideation (fSI), and without SIBs (fnonSIB). Structural (n = 91) and diffusion-weighted (n = 88) magnetic resonance imaging scans at baseline and SIB measures at follow-up on average two years later (standard deviation, SD = 1 year) were assessed in 92 females [age(SD) = 16.1(2.6) years] with bipolar disorder (BD, 28.3%) or major depressive disorder (MDD, 71.7%). One-way analyses of covariance comparing baseline regional grey matter cortical surface area, thickness, subcortical grey volumes, or white matter tensor-based fractional anisotropy across fSB (n = 40, 43.5%), fSI (n = 33, 35.9%) and fnonSIB (n = 19, 20.6%) groups were followed by pairwise comparisons in significant regions (p < 0.05). Compared to fnonSIBs, fSIs and fSBs showed significant decreases in cortical thickness of right inferior frontal gyrus pars orbitalis and middle temporal gyrus, fSIs of left inferior frontal gyrus, pars orbitalis. FSIs and fSBs showed lower fractional anisotropy in left uncinate fasciculus and corona radiata, and fSBs in right uncinate and superior fronto-occipital fasciculi. The study provides preliminary evidence of grey and white matter alterations in brain regions subserving emotional and behavioral regulation and perceptual processing in adolescent and young adult females with mood disorders with, versus without, future SIBs. Findings suggest potential targets to prevent SIBs in female adolescents and young adults.

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis

Background and purposeCerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). Design/methodsWe studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. ResultsDuring the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). ConclusionsIn this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.

Microstructural changes in the brain in persons with mild COVID-19

BACKGROUND: The purpose of which was to investigate, using voxel-based MR morphometry, changes in the volume of brain structures in persons who had undergone a new coronavirus disease.&#x0D; MATERIALS AND METHODS: 34 patients with mild COVID-19 between 4 months and one year were examined. All study participants were scanned at two time points: before COVID-19 infection and re-imaging after infection. The comparison group consisted of 30 healthy volunteers who did not have COVID-19 and were comparable in terms of sex, age, timing and MRI protocol.&#x0D; RESULTS: In the main and control groups a significant increase in the volume of individual segments of the large hemisphere cortex, subcortical gray matter, and white matter of the brain was detected. Signs of atrophic process were registered in the cerebellar cortex and left frontal lobe. In the main group there was an increase of cortical volume practically in all cerebral lobes with some emphasis on the posterior parts of the right hemisphere. When analyzing changes of subcortical gray matter in the main group, there was reliable (p 0.05) increase of its total volume due to left caudate nucleus, pale ball, right amygdala body and ventral diencephalon. Increased volume of white matter of the brain in COVID-19 patients was detected in the left isthmus and rostral part of the right cingulate gyrus, left paracentral lobe, and right precuneus.&#x0D; CONCLUSION: the cerebellum is affected quite early by SARS-CoV-2, as we recorded atrophic changes in its cortex at 412 months. In COVID-19, the microstructural integrity, predominantly of gray matter and other brain segments, is impaired. Increased volume of these structures indicates the duration of the inflammatory process. An increase in the volume of these structures may indicate the duration of the inflammatory process.

Performance evaluation of VRAIN: a brain-dedicated PET with a hemispherical detector arrangement

Objective. For PET imaging systems, a smaller detector ring enables less intrinsic spatial resolution loss due to the photon non-collinearity effect as well as better balance between production cost and sensitivity, and a hemispherical detector arrangement is more appropriate for brain imaging than a conventional cylindrical arrangement. Therefore, we have developed a brain-dedicated PET system with a hemispherical detector arrangement, which has been commercialized in Japan under the product name of VRAINTM. In this study, we evaluated imaging performance of VRAIN. Approach. The VRAIN used 54 detectors to form the main hemispherical unit and an additional half-ring behind the neck. Each detector was composed of a 12 × 12 array of lutetium fine silicate crystals (4.1 × 4.1 × 10 mm3) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm2 active area) with the one-to-one coupling. We evaluated the physical performance of VRAIN according to the NEMA NU 2–2018 standards. Some measurements were modified so as to fit the hemispherical geometry. In addition, we performed 18F-FDG imaging in a healthy volunteer. Main results. In the phantom study, the VRAIN showed high resolution for separating 2.2 mm rods, 229 ps TOF resolution and 19% scatter fraction. With the TOF gain for a 20 cm diameter object (an assumed head diameter), the peak noise-equivalent count rate was 144 kcps at 9.8 kBq ml−1 and the sensitivity was 25 kcps MBq−1. Overall, the VRAIN provided excellent image quality in phantom and human studies. In the human FDG images, small brain nuclei and gray matter structures were clearly visualized with high contrast and low noise. Significance. We demonstrated the excellent imaging performance of VRAIN, which supported the advantages of the hemispherical detector arrangement.

Specific Brain Gray Matter Volume Changes in Pediatric Complete Spinal Cord Injury without Fracture or Dislocation Using Voxel-Based Morphometry Analysis: Preliminary Results.

This study aims to investigate the brain gray matter volume (GMV) alterations of pediatric complete thoracolumbar spinal cord injury (SCI) without fracture or dislocation (SCIWOFD) using voxel-based morphometry (VBM) analysis and assess the sensitive neuroimaging biomarkers that may be surrogate targets to enhance brain plasticity. A total of 52 pediatric subjects (age range, 6-12 years), including 25 pediatric SCIWOFD patients and 27 typically developing (TD) children were recruited. An independent two-sample t test was performed to assess between-group differences of brain GMV. Partial correlation analyses were performed to explore the correlations between GMV values and The International Standards for Neurological Classification of Spinal Cord Injury scores, age at the time of injury, time after initial SCI. Receiver operating characteristic analysis was performed to compute the sensitivity and specificity of the imaging biomarkers for pediatric SCIWOFD diagnosis. As for the results, pediatric SCIWOFD patients showed significantly decreased GMV of bilateral cerebellum lobule VIII, right middle occipital gyrus and putamen (PUT), left pallidum (PAL) and thalamus, and increased GMV of vermis III, right cerebellum lobule VI, and supramarginal gyrus. In addition, GMV of left PAL and right PUT were negatively correlated with the pinprick/light touch sensory scores in pediatric SCIWOFD patients. Finally, when using the GMV values of left PAL and right PUT in combination as the predictor, area under the curve reached the highest-0.93. These findings provided evidence that the brain undergoes GMV changes after pediatric SCIWOFD, which may suggest important targets for functional remodeling after SCI in children and provide valuable information for the development of novel and effective rehabilitation therapies in the future.