Smaller Gray Matter Volume Research Articles

The association between isolated hypertension and brain volumes in UK Biobank

AbstractBackgroundHypertension is a well‐established risk factor for cognitive impairment, brain atrophy and dementia. Isolated hypertension is where either systolic or diastolic blood pressure is high and the other measure is normal. It is unknown the impact of isolated hypertension on brain atrophy and how it compares to non isolated hypertension (NIH). Therefore it is important to investigate the impact of isolated hypertension to help understand its impact on future dementia risk and cognitive decline. We investigated relationships between isolated hypertension on brain volumes using the largest cohort of healthy individuals from the United Kingdom.MethodUsing the UK Biobank cohort, we carried out a cross‐sectional study using 31,513 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models to determine the associations between isolated systolic (ISH) and isolated diastolic hypertension (IDH) split by BP medication use with brain volumes (total volume, total grey matter, hippocampal and white matter hyperintensities (WMH)).ResultIndividuals with ISH and taking BP medications (n = 3137) had smaller grey matter volumes (β = ‐0.04 [95%CI ‐0.07 to ‐0.03]), and greater WMH (β = 0.25 [95%CI 0.21 to 0.28]) compared to normotensive individuals (n = 14677). Interestingly, individuals with IDH and taking BP medications (n =140) also had smaller total grey matter (β = ‐0.11 [95%CI ‐0.19 to ‐0.04]) and larger WMH (β = 0.26 [95%CI 0.12 to 0.41]). Individuals with ISH have comparable total grey matter atrophy to individuals with NIH not taking medications (ISH β = ‐0.044 vs NIH β = ‐0.027) and have comparable WMHs (ISH β = 0.25 vs NIH β = 0.022).ConclusionOur results indicate that individuals with isolated hypertension have greater total grey matter atrophy and vascular pathology and this atrophy is similar to certain subsets of individuals with non isolated hypertension. These results provide a further emphasis of preventative strategies particularly focusing on isolated systolic hypertension as well as non isolated hypertension in maintaining brain health to reduce dementia risk earlier in life.

Abstract 13245: Cardiovascular Risk Burden in Relation to Dementia and Brain Structural Imaging Markers: A Study From UK Biobank

Introduction: Cardiovascular risk burden is associated with higher all-cause dementia risk. However, the roles of cardiovascular disease (CVD) and genetic background, and the associations of cardiovascular risk burden with dementia subtypes and brain structure, need to be examined. Hypothesis: We hypothesized that the Framingham General Cardiovascular Risk Score (FGCRS) would be associated with all-cause and subtypes of dementia and brain structure. Methods: We conducted a prospective study among 354,654 participants free of CVD and dementia at baseline (2006-2010, mean age 56.4 years) within UK Biobank. CVD risk burden was evaluated by baseline FGCRS. Dementia case was identified from hospital inpatient records and death register data. Brain MRI volume markers were available for 15,104 participants since 2014. Logistic and linear regression models were used for dementia risk and brain volumes, respectively. Results: During a median 12.0 years of follow-up, 3,996 all-cause dementia cases were identified. Higher FGCRS was associated with an increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors, and polygenic risk score (PRS) of Alzheimer’s disease (AD). Comparing the high vs. low tertile of FGCRS, the odds ratios (ORs) and 95% CIs were 1.26 (1.12, 1.42) for all-cause dementia, 1.67 (1.33, 2.09) for AD, and 1.53 (1.08, 2.17) for vascular dementia (all P trend < 0.05). Incident stroke and coronary heart disease accounted for 13% (95% CI: 9%, 19%) of the association of FGCRS with all-cause dementia. Interaction was not detected for FGCRS and PRS on risk of all-cause or any subtype of dementia (all P for interaction > 0.05). We observed an 83% (95% CI: 47%, 128%) higher all-cause dementia risk comparing the high-high vs. low-low for FGCRS-PRS category. For standardized brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume, and smaller grey matter volume. Conclusions: Cardiovascular risk burden was associated with higher dementia risk and neurodegeneration-related brain volume markers. The association of cardiovascular risk burden with all-cause dementia was partly explained by CVD onset and independent of dementia genetic risk.

The Association of Age at Diagnosis of Hypertension With Brain Structure and Incident Dementia in the UK Biobank.

[Figure: see text].

Social Isolation is Associated With Smaller Grey Matter Volumes in Amygdala in People With Major Depression: A U.K. Biobank Study

Social Isolation is Associated With Smaller Grey Matter Volumes in Amygdala in People With Major Depression: A U.K. Biobank Study

Body fat, cardiovascular risk factors and brain structure in school-age children.

In adults, cardiovascular risk factors are known to be associated with brain health. We hypothesized that these associations are already present at school-age. We examined the associations of adverse body fat measures and cardiovascular risk factors with brain structure, including volumetric measures and white matter microstructure, in 10-year-old children. We performed a cross-sectional analysis in a population-based prospective cohort study in Rotterdam, the Netherlands. Analyses were based on 3098 children aged 10 years with neuroimaging data and at least one measurement of body fat and cardiovascular risk factors. Body fat measures included body mass index (BMI), fat mass index and android fat mass percentage obtained by Dual-energy X-ray absorptiometry. Cardiovascular risk factors included blood pressure, and serum glucose, insulin and lipids blood concentrations. Structural neuroimaging, including global and regional brain volumes, was quantified by magnetic resonance imaging. DTI was used to assess white matter microstructure, including global fractional anisotropy (FA) and mean diffusivity (MD). As compared to children with a normal weight, those with underweight had a smaller total brain and white matter volumes (differences -18.10 (95% Confidence Interval (CI) -30.97,-5.22) cm3, -10.64 (95% CI -16.82,-4.47) cm3, respectively). In contrast, one SDS (Standard Deviation Score) increase in fat mass index was associated with a smaller gray matter volume (differences -3.48 (95% CI -16.82, -4.47) cm3). Also, one SDS increase in android fat mass percentage was associated with lower white matter diffusivity (difference -0.06 (95% CI -0.10, -0.02) SDS). None of the other cardiovascular risk factors were associated with any of the brain outcomes. Body fat measures, but not other cardiovascular risk factors, were associated with structural neuroimaging outcomes in school-aged children. Prospective studies are needed to assess causality, direction and long-term consequences of the associations.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project

ObjectiveWhile gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. MethodSubjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. ResultsThere were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. ConclusionMDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Neural correlates of irritability in a community sample of children

Irritability has been associated with aberrant patterns of neural activation, yet little is known about structural brain correlates of irritability. As such, we aimed to investigate associations between irritability and gray matter volume (GMV) in a community sample of children enriched for irritability. The sample comprised children (n=162) aged 9-11 years with and without Attention-Deficit/Hyperactivity Disorder (ADHD), participating in a cohort study with magnetic resonance imaging data available. Mixed effects linear regression analyses tested the associations between irritability symptoms and regional GMV (extracted using Freesurfer). Irritability was associated with smaller gray matter volume across multiple brain regions implicated in executive functioning, and emotion and reward processing including frontal regions and the cingulate.

Gray matter abnormalities in Tourette Syndrome: a meta-analysis of voxel-based morphometry studies

Tourette syndrome (TS) is a neurobehavioral disorder for which the neurological mechanism has not been elucidated. Voxel-based morphometry (VBM) studies have revealed abnormalities in gray matter volume (GMV) in patients with TS; however, consistent results have not been obtained. The current study attempted to provide a voxel wise meta-analysis of gray matter changes using seed-based d mapping (SDM). We identified ten relevant studies that investigated gray matter alterations in TS patients and performed a meta-analysis using the SDM method to quantitatively estimate regional gray matter abnormalities. Next, we examined the relationships between GMV abnormalities and demographic and clinical characteristics. Our results demonstrated that TS patients had smaller GMV in the bilateral inferior frontal gyri and greater GMV in the cerebellum, right striatum (putamen), and bilateral thalami (pulvinar nucleus) than healthy controls. A meta-regression analysis did not identify correlations between GMV changes and demographic or clinical variables. This meta-analysis confirmed significant and consistent GMV changes in several brain regions of TS patients, primarily in the cortico-striato-thalamo-cortical network.

Decreased grey matter volumes in unaffected mothers of individuals with autism spectrum disorder reflect the broader autism endophenotype

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an early onset and a strong genetic origin. Unaffected relatives may present similar but subthreshold characteristics of ASD. This broader autism phenotype is especially prevalent in the parents of individuals with ASD, suggesting that it has heritable factors. Although previous studies have demonstrated brain morphometry differences in ASD, they are poorly understood in parents of individuals with ASD. Here, we estimated grey matter volume in 45 mothers of children with ASD (mASD) and 46 age-, sex-, and handedness-matched controls using whole-brain voxel-based morphometry analysis. The mASD group had smaller grey matter volume in the right middle temporal gyrus, temporoparietal junction, cerebellum, and parahippocampal gyrus compared with the control group. Furthermore, we analysed the correlations of these brain volumes with ASD behavioural characteristics using autism spectrum quotient (AQ) and systemizing quotient (SQ) scores, which measure general autistic traits and the drive to systemize. Smaller volumes in the middle temporal gyrus and temporoparietal junction correlated with higher SQ scores, and smaller volumes in the cerebellum and parahippocampal gyrus correlated with higher AQ scores. Our findings suggest that atypical grey matter volumes in mASD may represent one of the neurostructural endophenotypes of ASD.

The association between latent trauma and brain structure in children

The developing brain is marked by high plasticity, which can lead to vulnerability to early life stressors. Previous studies indicate that childhood maltreatment is associated with structural aberrations across a number of brain regions. However, prior work is limited by small sample sizes, heterogeneous age groups, the examination of one structure in isolation, the confounding of different types of early life stressors, and not accounting for socioeconomic status. These limitations may contribute to high variability across studies. The present study aimed to investigate how trauma is specifically associated with cortical thickness and gray matter volume (GMV) differences by leveraging a large sample of children (N = 9270) from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). A latent measure of trauma exposure was derived from DSM-5 traumatic events, and we related this measure of trauma to the brain using structural equation modeling. Trauma exposure was associated with thinner cortices in the bilateral superior frontal gyri and right caudal middle frontal gyrus (pfdr-values < .001) as well as thicker cortices in the left isthmus cingulate and posterior cingulate (pfdr-values ≤ .027), after controlling age, sex, and race/ethnicity. Furthermore, trauma exposure was associated with smaller GMV in the right amygdala and right putamen (pfdr-values ≤ .048). Sensitivity analyses that controlled for income and parental education were largely consistent with the main findings for cortical thickness. These results suggest that trauma may be an important risk factor for structural aberrations, specifically for cortical thickness differences in frontal and cingulate regions in children.

Individualized brain development and cognitive outcome in infants with congenital heart disease.

Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development–Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease.

Prefrontal cortex and amygdala anatomy in youth with persistent levels of harsh parenting practices and subclinical anxiety symptoms over time during childhood

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia.

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.

Gray Matter Atrophy in the Cortico-Striatal-Thalamic Network and Sensorimotor Network in Relapsing-Remitting and Primary Progressive Multiple Sclerosis.

Gray matter atrophy in multiple sclerosis (MS) is thought to be associated with disability and cognitive impairment, but previous studies have sometimes had discordant results, and the atrophy patterns of relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) remain to be clarified. We conducted a meta-analysis using anisotropic effect-size-based algorithms (AES-SDM) to identify consistent findings from whole-brain voxel-based morphometry (VBM) studies of gray matter volume (GMV) in 924 RRMS patients and 204 PPMS patients. This study is registered with PROSPERO (number CRD42019121319). Compared with healthy controls, RRMS and PPMS patients showed gray matter atrophy in the cortico-striatal-thalamic network, sensorimotor network, and bilateral insula. RRMS patients had a larger GMV in the left insula, cerebellum, right precentral gyrus, and bilateral putamen as well as a smaller GMV in the bilateral cingulate, caudate nucleus, right thalamus, superior temporal gyrus and left postcentral gyrus than PPMS patients. The disease duration, Expanded Disability Status Scale score, Paced Auditory Serial Addition Test z-score, and T2-weighted lesion load were associated with specific gray matter regions in RRMS or PPMS. Alterations in the cortico-striatal-thalamic networks, sensorimotor network, and insula may be involved in the common pathogenesis of RRMS and PPMS. The deficits in the cingulate gyrus and caudate nucleus are more apparent in RRMS than in PPMS. The more severe cerebellum atrophy in PPMS may be a brain feature associated with its neurological manifestations. These imaging biomarkers provide morphological evidence for the pathophysiology of MS and should be verified in future research.

Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents.

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.

Cardiovascular Risk Burden in Relation to Dementia and Brain Structural and Metabolic Imaging Markers

Background: The roles of cardiovascular disease (CVD) and dementia genetic predisposition in the association of cardiovascular risk burden with dementia need to be elucidated. Relevant evidence regarding the brain structural and metabolic pathways underlying this association is scarce. Methods: We conducted a prospective cohort study among 354,654 participants free of baseline CVD and dementia (2006-2010, mean age 56.4 years) within UK Biobank (UKB); brain MRI measurement was available for 15,104 participants since 2014. Cardiovascular risk burden was evaluated by baseline Framingham General Cardiovascular Risk Score (FGCRS); polygenic risk score (PRS) was constructed from common Alzheimer’s disease (AD) variants. Incident dementia was identified from hospital inpatient and death register data. The associations of cardiovascular risk burden with brain glucose uptake indices were evaluated cross-sectionally among 304 individuals free of CVD and cancer with 18F-FDG PET/CT scan measurement in a hospital-based study in China. Findings: During a median 12.0-year follow-up, 3,998 all-cause dementia cases were identified in UKB. Higher FGCRS was associated with increased all-cause dementia risk after controlling for demographic, major lifestyle, clinical factors, and PRS. The corresponding ORs (95% CIs) across increasing FGCRS tertiles were1.00 (ref), 1.10 (0.98, 1.23), and 1.26 (1.12, 1.41) (Ptrend 0.05). Regarding the joint association of FGCRS and PRS with all-cause dementia, we observed an 83% (95% CI: 47%, 128%) higher risk comparing the high-high vs. low-low category. For standardized brain volumes, higher FGCRS was associated with greater white matter hyperintensities (log-transformed), and smaller grey matter volume and cortical volume. FGCRS was inversely associated with the glucose uptake level in all brain lobes and total grey matter. Interpretation: Higher cardiovascular risk burden was associated with higher dementia risk and neurodegeneration-related brain volumes and lower glucose uptake in brain. The association of cardiovascular risk burden with all-cause dementia was partially mediated by CVD onset and independent of dementia genetic risk. Funding: National Key Research and Development Plan of China, Zhejiang University Education Foundation Global Partnership Fund, National Science Fund for Excellent Young Scholars, and Talent Introduction Programme of Chinese Academy of Sciences. Declaration of Interest: None to declare. Ethical Approval: This study received ethical approval from the North West Multi-center Research Ethics Committee (REC reference: 16/NW/0274).

Cortical thickness and subcortical volume abnormalities in male crack-cocaine users

Crack-cocaine offers a higher risk of abuse than intranasal and intravenous use of cocaine. Yet, current treatments remain disappointing and our understanding of the mechanism of crack-cocaine neurotoxicity is still incomplete. Magnetic resonance images studies on brain changes of crack-cocaine addicts show divergent data. The present study investigated gray matter (GM) abnormalities in crack-cocaine dependents (n = 18) compared to healthy controls (n = 17). MRI data was analysed using FreeSurfer and voxel-based morphometry (VBM). FreeSurfer analysis showed that CD had decreased cortical thickness (CT) in the left inferior temporal cortex (lTC), left orbitofrontal cortex (lOFC) and left rostro frontal cortex (lRFC), enlargement in left inferior lateral ventricle, and smaller GM volume in right hippocampus and right ventral diencephalon. VBM analysis showed that CD had significantly decreased GM volume in left Putamen and left nucleus accumbens. Furthermore, we found a negative correlation between duration of crack-cocaine use and lTC CT. These results provide compelling evidence for GM abnormalities in CD and also suggest that duration of crack-cocaine use may be associated with CT alterations.

A longitudinal observational population-based study of brain volume associated with changes in sleep timing from middle to late-life.

Sleep behaviors are related to brain structure and function, but the impact of long-term changes in sleep timing on brain health has not been clearly addressed. The purpose of this study was to examine the association of longitudinal changes in sleep timing from middle to late-life with gray matter volume (GMV), an important marker of brain aging. We enrolled 1798 adults (aged 49-82 years, men 54.6%) who underwent magnetic resonance imaging (MRI) between 2011 and 2014. Midsleep time (MST) on free days corrected for sleep debt on workdays was adopted as a marker of sleep timing. Data on MST were available at the time of MRI assessment and at examinations that were given 9 years earlier (2003-2004). Longitudinal changes in MST over the 9-year period were derived and categorized into quartiles. Subjects in quartile 1 were defined as "advancers" (MST advanced ≥ 1 h) while those in quartile 4 were defined as "delayers" (MST delayed ≥ 0.2 h). Quartiles 2-3 defined a reference group (MST change was considered modest). The relationship of GMV with MST changes over 9 years was investigated. Nine-year change in MST were significantly associated with GMV. Compared to the reference group, advancers had smaller GMVs in the frontal and temporal regions. A delay in MST was also associated with smaller cerebellar GMV. In middle-to-late adulthood, the direction of change in MST is associated with GMV. While advancers and delayers in MST tend to present lower GMV, associations appear to differ across brain regions.

Chemotherapy-induced grey matter abnormalities in cancer survivors: a voxel-wise neuroimaging meta-analysis.

Findings regarding chemotherapy-induced grey matter abnormalities are heterogeneous, and no meta-analysis has quantitatively assessed brain structural alterations in cancer survivors treated with chemotherapy. To investigate the grey matter abnormalities in non-CNS (central nervous system) cancer survivors treated with chemotherapy using Anisotropic Effect Size Signed Differential Mapping (AES-SDM) software. We identified studies published up to Sep 2018 that compared grey matter in non-CNS cancer survivors treated with chemotherapy (CT+, 10 data sets including 433 individuals) and cancer survivors not treated with chemotherapy (CT-, 7 data sets including 210 individuals) or healthy controls (HC, 3 data sets including 407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Compared with both CT- and HC, the CT + groups exhibited a reduced grey matter volume (GMV), mainly in the prefrontal and anterior cingulate cortex (ACC) and right fusiform gyrus (FG). A smaller GMV in the FG and prefrontal cortex were found in the CT + compared with the CT-groups and in the CT + groups with impaired cognition. GMV in two areas was positively associated with the time since chemotherapy. The present results suggest that non-CNS cancer survivors treated with chemotherapy exhibit grey matter abnormalities in the brain, especially in the prefrontal and ACC cortex. Grey matter volume changes after chemotherapy may contribute to cognitive impairments in cancer survivors that can be observed after chemotherapy.

Smaller caudate gray matter volume is associated with greater implicit suicidal ideation in depressed adolescents

BackgroundObjective biomarkers of cognitive vulnerabilities related to suicidal ideation (SI) may assist in early prevention in adolescents. Previously, we found that smaller gray matter volumes (GMVs) of the dorsal striatum prospectively predicted implicit SI, measured using a computerized implicit association test (IAT) assessing associations between “self” and “death,” in a community sample of adolescents. Here, we sought to replicate these findings in an independent sample of depressed adolescents. Methods53 depressed adolescents who varied in severity of suicidal thoughts and behaviors completed high-resolution structural MRI. Caudate, putamen, and nucleus accumbens GMVs were estimated using FreeSurfer 6.0. Robust linear regressions were used to examine associations between striatal GMVs and implicit and explicit SI, covarying for sex, age, total intracranial volume, medication use, and depression severity. Significance was determined using Bonferroni correction. Finally, LASSO regression was used to identify which striatal GMV contributed most to prediction of implicit SI. ResultsSmaller bilateral caudate and right nucleus accumbens GMVs were associated with higher IAT scores (all ps<0.001). Smaller putamen and nucleus accumbens GMVs were not associated with implicit or explicit SI. Our LASSO analysis indicated that right caudate GMV contributed most to the prediction of IAT scores. ConclusionsThis study is the first to demonstrate that caudate GMVs are significantly associated with implicit self-associations with death in a sample of depressed adolescents. When considered with our previous work, smaller caudate GMVs may be a robust biomarker of implicit SI in adolescents, with clinical implications for early identification of youth at risk for engaging in suicidal behaviors.