Gray Matter Deficits Research Articles

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

IntroductionRegional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.Methods15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.ResultsCompared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges’ g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.ConclusionEOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Relationships between AD‐related neuroanatomy and cognitive, physical, and social aging in vervet monkeys

AbstractBackgroundIn humans, social integration wanes with age, a pattern hypothesized to stem from cognitive or physical decrements. Social isolation increases dementia risk. Nonhuman primates provide important translational opportunities to study brain‐body relationships that may promote healthy or pathological aging. Vervet monkeys (Chlorocebus sabaeus), like humans, have complex central nervous systems and naturally experience cognitive, functional, and neuroanatomical changes with age. These changes often recapitulate characteristics of early Alzheimer’s disease (AD), including Aβ accumulation in the brain, reduced CSF Aβ, and greater Aβ plaque burdens accompanied by reduced brain volumes.MethodWe studied 25 females, aged 8‐29 years (middle to very old‐aged), living in long term, stable, social groups. Using a cross‐sectional study design, we tested whether cognitive (executive function and working memory) or physical (gait speed) function mediated the effects of age on social behavior. We also used T1‐weighted structural MRI to test whether the cortical thickness of an AD‐signature region of interest (“meta‐ROI”) predicted social participation at one year follow‐up.ResultCognitive (executive function: b = ‐0.603; p = 0.038; working memory: b = ‐0.537; p<0.001) and physical (gait speed: (b = ‐1.005; p = 0.043) function were negatively associated with age. Time spent in affiliative behavior was inversely related to age (b = ‐0.723; p = 0.009), whereas time spent alone was higher for older‐aged monkeys (b = 0.723; p = 0.009). Time spent grooming others decreased with age (b = ‐0.217; p<0.001), but time receiving grooming did not (b = ‐0.057; p = 0.333). The number of social partners groomed diminished in aged subjects (b = ‐0.145; p<0.001). The relationships between age and sociality were mediated, in part, by cognitive function: higher degrees of executive function had a positive mediating effect on time spent in grooming interactions (b = 0.120; p = 0.047). Conversely, social participation was not mediated by physical performance. Finally, thinner cortices in the meta‐ROI predicted greater social isolation (t = ‐2.199; p = 0.038) and fewer numbers of social partners (z = ‐2.319; p = 0.020) at one year follow‐up.ConclusionThese results suggest that: 1) cognitive, physical, and social function of vervets decline with age like humans; 2) aging vervets are not socially excluded but decreasingly engage in social behavior; and 3) cognitive deficits stemming from cortical gray matter deficits may underlie the relationship between aging and social decline.

Cerebrovascular Function is Altered in Hemodialysis Patients.

Hemodialysis (HD) patients have declines in cerebral blood flow (CBF) and cerebral oxygenation during HD that may lead to ischemic brain injury. Cerebrovascular reactivity (CVR) may indicate which individuals are more susceptible to intradialytic hypoperfusion and ischemia. We hypothesized that HD patients would have decreased CVR and increased CBF relative to controls and deficits in CVR would be related to brain structural deficits. We measured cortical thickness and white matter hyperintensity (WMH) volume from T1 and T2 FLAIR images respectively, CVR from a breath hold BOLD CVR fMRI and arterial transit time (ATT) and CBF from ASL. Cerebrovascular and structural deficits in gray and white matter (GM and WM) were tested by averaging across the tissue and with a pothole analysis. Finally, we correlated cortical thickness and WMH volume with GM and WM cerebrovascular variables to assess the relationship between brain structure and cerebrovascular health. In ten HD patients, cortical thickness was found to be decreased (p= 0.002), WMH volume increased (p=0.004), and WM CBF increased (p=0.02) relative to ten controls. Pothole analysis indicated a higher number of increased GM and WM CBF voxels (p=0.03, p=0.02) and a higher number of decreased GM and WM CVR voxels (p=0.02, p=0.01). This pilot study demonstrates that HD patients have decreased CVR and increased CBF relative to controls, along with reduced brain integrity. Further investigation is required to fully understand if these cerebrovascular deficits may lead to structural changes.

The medullary serotonergic centres involved in cardiorespiratory control are disrupted by fetal growth restriction.

Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem cardiorespiratory control centres. The primary neurons that release serotonin reside in the brainstem cardiorespiratory control centres and may be affected by FGR. At two time points in the last trimester of sheep brain development, 110 and 127days of gestation (0.74 and 0.86 of gestation), we assessed histopathological alterations in the brainstem cardiorespiratory control centres of the pons and medulla in early-onset FGR versus control fetal sheep. The FGR cohort were hypoxaemic and asymmetrically growth restricted. Compared to the controls, the brainstem of FGR fetuses exhibited signs of neuropathology, including elevated cell death and reduced cell proliferation, grey and white matter deficits, and evidence of oxidative stress and neuroinflammation. FGR brainstem pathology was predominantly observed in the medullary raphé nuclei, hypoglossal nucleus, nucleus ambiguous, solitary tract and nucleus of the solitary tract. The FGR groups showed imbalanced brainstem serotonin and serotonin 1A receptor abundance in the medullary raphé nuclei, despite evidence of increased serotonin staining within vascular regions of placentomes collected from FGR fetuses. Our findings demonstrate both early and adaptive brainstem neuropathology in response to placental insufficiency. KEY POINTS: Early-onset fetal growth restriction (FGR) was induced in fetal sheep, resulting in chronic fetal hypoxaemia. Growth-restricted fetuses exhibit persistent neuropathology in brainstem nuclei, characterised by disrupted cell proliferation and reduced neuronal cell number within critical centres responsible for the regulation of cardiovascular and respiratory functions. Elevated brainstem inflammation and oxidative stress suggest potential mechanisms contributing to the observed neuropathological changes. Both placental and brainstem levels of 5-HT were found to be impaired following FGR.

Functional connectivity and gray matter deficits within the auditory attention circuit in first-episode psychosis.

Selective attention deficits in first episode of psychosis (FEP) can be indexed by impaired attentional modulation of auditory M100. It is unknown if the pathophysiology underlying this deficit is restricted to auditory cortex or involves a distributed attention network. We examined the auditory attention network in FEP. MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while alternately ignoring or attending tones. A whole-brain analysis of MEG source activity during auditory M100 identified non-auditory areas with increased activity. Time-frequency activity and phase-amplitude coupling were examined in auditory cortex to identify the attentional executive carrier frequency. Attention networks were defined by phase-locking at the carrier frequency. Spectral and gray matter deficits in the identified circuits were examined in FEP. Attention-related activity was identified in prefrontal and parietal regions, markedly in precuneus. Theta power and phase coupling to gamma amplitude increased with attention in left primary auditory cortex. Two unilateral attention networks were identified with precuneus seeds in HC. Network synchrony was impaired in FEP. Gray matter thickness was reduced within the left hemisphere network in FEP but did not correlate with synchrony. Several extra-auditory attention areas with attention-related activity were identified. Theta was the carrier frequency for attentional modulation in auditory cortex. Left and right hemisphere attention networks were identified, with bilateral functional deficits and left hemisphere structural deficits, though FEP showed intact auditory cortex theta phase-gamma amplitude coupling. These novel findings indicate attention-related circuitopathy early in psychosis potentially amenable to future non-invasive interventions.

Additive cortical gray matter deficits in people living with HIV who use cocaine.

Cocaine use, which is disproportionately common in people living with HIV (PWH), is known to have neurotoxic effects that may exacerbate HIV neuropathogenesis. While both cocaine use and HIV disease are independently associated with deficits in gray matter (GM) volume, the additive effect of cocaine use to HIV disease on GM volume has not been explored. Here, we investigated subcortical and cortical brain volume differences between four groups of individuals with and without HIV disease and/or cocaine use. Participants also completed a comprehensive neuropsychological testing battery, and HIV disease characteristics were recorded. Within subcortical regions, cocaine use was independently associated with higher volume in the dorsal striatum and pallidum, while HIV disease was associated with lower volume in the nucleus accumbens and thalamus. For cortical regions, there was an additive effect of cocaine use on HIV disease in parietal and occipital lobe volume with PWH who used cocaine displaying the lowest GM volume. Within regions that differed between groups, higher neurocognitive function was positively associated with thalamic, nucleus accumbens, dorsal striatum, and occipital lobe volume. For regions that showed a significant main effect of HIV disease, lower nadir CD4 + T cell count was associated with lower nucleus accumbens and occipital lobe volume. Lower current CD4 + T cell count was associated with lower occipital lobe volume. These results suggest that PWH who use cocaine are at greater risk for cortical atrophy than cocaine use or HIV disease alone.

The two-network framework of number processing: a step towards a better understanding of the neural origins of developmental dyscalculia

Developmental dyscalculia is a specific learning disorder that persists over lifetime and can have an enormous impact on personal, health-related, and professional aspects of life. Despite its central importance, the origin both at the cognitive and neural level is not yet well understood. Several classification schemas of dyscalculia have been proposed, sometimes together with an associated deficit at the neural level. However, these explanations are (a) not providing an exhaustive framework that is at levels with the observed complexity of developmental dyscalculia at the behavioral level and (b) are largely mono-causal approaches focusing on gray matter deficits. We suggest that number processing is instead the result of context-dependent interaction of two anatomically largely separate, distributed but overlapping networks that function/cooperate in a closely integrated fashion. The proposed two-network framework (TNF) is the result of a series of studies in adults on the neural correlates underlying magnitude processing and arithmetic fact retrieval, which comprised neurofunctional imaging of various numerical tasks, the application of probabilistic fiber tracking to obtain well-defined connections, and the validation and modification of these results using disconnectome mapping in acute stroke patients. Emerged from data in adults, it represents the endpoint of the acquisition and use of mathematical competencies in adults. Yet, we argue that its main characteristics should already emerge earlier during development. Based on this TNF, we develop a classification schema of phenomenological subtypes and their underlying neural origin that we evaluate against existing propositions and the available empirical data.

Clinical and cortical similarities identified between bipolar disorder I and schizophrenia: A multivariate approach.

Structural neuroimaging studies have identified similarities in the brains of individuals diagnosed with schizophrenia (SZ) and bipolar I disorder (BP), with overlap in regions of gray matter (GM) deficits between the two disorders. Recent studies have also shown that the symptom phenotypes associated with SZ and BP may allow for a more precise categorization than the current diagnostic criteria. In this study, we sought to identify GM alterations that were unique to each disorder and whether those alterations were also related to unique symptom profiles. We analyzed the GM patterns and clinical symptom presentations using independent component analysis (ICA), hierarchical clustering, and n-way biclustering in a large (N ∼ 3,000), merged dataset of neuroimaging data from healthy volunteers (HV), and individuals with either SZ or BP. Component A showed a SZ and BP < HV GM pattern in the bilateral insula and cingulate gyrus. Component B showed a SZ and BP < HV GM pattern in the cerebellum and vermis. There were no significant differences between diagnostic groups in these components. Component C showed a SZ < HV and BP GM pattern bilaterally in the temporal poles. Hierarchical clustering of the PANSS scores and the ICA components did not yield new subgroups. N-way biclustering identified three unique subgroups of individuals within the sample that mapped onto different combinations of ICA components and symptom profiles categorized by the PANSS but no distinct diagnostic group differences. These multivariate results show that diagnostic boundaries are not clearly related to structural differences or distinct symptom profiles. Our findings add support that (1) BP tend to have less severe symptom profiles when compared to SZ on the PANSS without a clear distinction, and (2) all the gray matter alterations follow the pattern of SZ < BP < HV without a clear distinction between SZ and BP.

Altered striatal functional connectivity and structural dysconnectivity in individuals with bipolar disorder: A resting state magnetic resonance imaging study

Bipolar disorder (BD) is a mood swing illness characterized by episodes ranging from depressive lows to manic highs. Although the specific origin of BD is unknown, genetics, environment, and changes in brain structure and chemistry may all have a role. Through magnetic resonance imaging (MRI) evaluations, this study looked into functional abnormalities involving the striatum between BD group and healthy controls (HC), compared the whole-brain gray matter (GM) morphological patterns between the groups and see whether functional connectivity has its underlying structural basis. We applied sliding windows to functional magnetic resonance imaging (fMRI) data from 49 BD patients and 44 HCs to generate temporal correlations maps to determine strength and variability of the striatum-to-whole-brain-network functional connectivity (FC) in each window whilst also employing voxel-based morphometry (VBM) to high-resolution structural MRI data to uncover structural differences between the groups. Our analyses revealed increased striatal connectivity in three consecutive windows 69, 70, and 71 (180, 182, and 184 s) in individuals with BD (p < 0.05; Bonferroni corrected) in fMRI images. Moreover, the VBM findings of structural images showed gray matter (GM) deficits in the left precentral gyrus and middle frontal gyrus of the BD patients (p = 0.001, uncorrected) when compared to HCs. Variability of striatal connectivity did not reveal significant differences between the groups. These findings revealed that BD was associated with a weakening of the precentral gyrus and middle frontal gyrus, also implying that bipolar illness may be linked to striatal functional brain alterations.

Gray matter abnormalities and associated familial risk endophenotype in individuals with first-episode bipolar disorder: Evidence from whole-brain voxel-wise meta-analysis.

Gray matter abnormalities have been widely reported in individuals with and at familial risk for bipolar disorder (BD). However, inconsistent findings were reported, and whether shared abnormalities exist between at-risk individuals and patients which can represent an endophenotype remained unclear. This meta-analysis aimed at identifying robust patterns of gray matter changes in patients with first-episode BD (FEBD) and associated risk endophenotype of BD. A systematic literature search was performed to identify eligible voxel-based morphometry studies comparing FEBD patients and healthy controls. Findings of included studies were integrated using the Seed-based d Mapping toolbox. Common and distinct patterns of gray matter abnormalities between FEBD patients and unaffected at-risk individuals were explored. A total of 16 VBM studies comparing 411 FEBD patients and 521 controls were included. FEBD patients showed increased gray matter volume in the cerebellum, posterior cingulate cortex and striatum, and decreased gray matter volume in the medial superior frontal gyrus and gyrus rectus. No common abnormalities were identified between FEBD patients and unaffected at-risk individuals. More gray matter loss in the medial superior frontal gyrus and insula were found in FEBD patients relative to unaffected at-risk individuals. These findings revealed robust gray matter abnormalities in the cortico-striato-cerebellar and default mode network regions in FEBD, and implicated that gray matter deficits may not represent a familial risk endophenotype of BD.

Gray Matter Deficits of Cortical-striatal-limbic Circuit in Social Anxiety Disorder

IntroductionThe extant findings have been of great heterogeneity due to partial volume effects in the investigation of cortical gray matter volume (GMV), high comorbidity with other psychiatric disorders, and concomitant therapy in the neuroimaging studies of social anxiety disorder (SAD).Objectives To identity gray matter deficits in cortical and subcortical structures in non-comorbid never-treated patients, so as to explore the “pure” SAD-specific pathophysiology and neurobiology.Methods Thirty-two non-comorbid free-of-treatment patients with SAD and 32 demography-matched healthy controls were recruited to undergo high-resolution 3.0-Tesla T1-weighted MRI. Cortical thickness (CT) and subcortical GMV were estimated using FreeSurfer; then the whole-brain vertex-wise analysis was performed to compare group differences in CT. Besides, differences in subcortical GMV of priori selected regions-of-interest: amygdala, hippocampus, putamen, and pallidum were compared by an analysis of covariance with age, gender, and total subcortical GMV as covariates.ResultsThe SAD patients demonstrated significantly decreased CT near-symmetrically in the bilateral prefrontal cortex (Monte Carlo simulations of P &lt; 0.05). Besides, smaller GMV in the left hippocampus and pallidum were also observed in the SAD cohort (two-sample t-test of P &lt; 0.05).ConclusionsFor the first time, the current study investigated the structural alterations of CT and subcortical GMV in non-comorbid never-treated patients with SAD. Our findings provide preliminary evidences that structural deficits in cortical-striatal-limbic circuit may contribute to the psychopathological basis of SAD, and offer more detailed structural substrates for the involvement of such aberrant circuit in the imbalance between defective bottom-up response and top-down control to external stimuli in SAD.DisclosureNo significant relationships.

P181. Cortical Similarities Between Bipolar I Disorder and Schizophrenia: A Multivariate Approach

Schizophrenia (SZ) and bipolar disorder (BP) have similar gray matter (GM) deficits, though SZ effects are generally larger. GM differences between the disorders have not been thoroughly examined using a multivariate approach.

Four-modality imaging of unmedicated subjects with schizophrenia: 18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, and MRI

Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.

Lower regional grey matter in alcohol use disorders: evidence from a voxel-based meta-analysis

BackgroundPrevious research using whole-brain neuroimaging techniques has revealed structural differences of grey matter (GM) in alcohol use disorder (AUD) patients. However, some of the findings diverge from other neuroimaging studies and require further replication. The quantity of relevant research has, thus far, been limited and the association between GM and abstinence duration of AUD patients has not yet been systematically reviewed.MethodsThe present research conducted a meta-analysis of voxel-based GM studies in AUD patients published before Jan 2021. The study utilised a whole brain-based d-mapping approach to explore GM changes in AUD patients, and further analysed the relationship between GM deficits, abstinence duration and individual differences.ResultsThe current research included 23 studies with a sample size of 846 AUD patients and 878 controls. The d-mapping approach identified lower GM in brain regions including the right cingulate gyrus, right insula and left middle frontal gyrus in AUD patients compared to controls. Meta-regression analyses found increasing GM atrophy in the right insula associated with the longer mean abstinence duration of the samples in the studies in our analysis. GM atrophy was also found positively correlated with the mean age of the samples in the right insula, and positively correlated with male ratio in the left middle frontal gyrus.ConclusionsGM atrophy was found in the cingulate gyrus and insula in AUD patients. These findings align with published meta-analyses, suggesting they are potential deficits for AUD patients. Abstinence duration, age and gender also affect GM atrophy in AUD patients. This research provides some evidence of the underlying neuroanatomical nature of AUD.

Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.

Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

Assessment of brain cholesterol metabolism biomarker 24S-hydroxycholesterol in schizophrenia

Plasma 24S-hydroxycholesterol mostly originates in brain tissue and likely reflects the turnover of cholesterol in the central nervous system. As cholesterol is disproportionally enriched in many key brain structures, 24S-hydroxycholesterol is a promising biomarker for psychiatric and neurologic disorders that impact brain structure. We hypothesized that, as schizophrenia patients have widely reported gray and white matter deficits, they would have abnormal levels of plasma 24S-hydroxycholesterol, and that plasma levels of 24S-hydroxycholesterol would be associated with brain structural and functional biomarkers for schizophrenia. Plasma levels of 24S-hydroxycholesterol were measured in 226 individuals with schizophrenia and 204 healthy controls. The results showed that levels of 24S-hydroxycholesterol were not significantly different between patients and controls. Age was significantly and negatively correlated with 24S-hydroxycholesterol in both groups, and in both groups, females had significantly higher levels of 24S-hydroxycholesterol compared to males. Levels of 24S-hydroxycholesterol were not related to average fractional anisotropy of white matter or cortical thickness, or to cognitive deficits in schizophrenia. Based on these results from a large sample and using multiple brain biomarkers, we conclude there is little to no value of plasma 24S-hydroxycholesterol as a brain metabolite biomarker for schizophrenia.

NCOG-72. DIFFERENTIAL EFFECTS OF SURGERY AND CHEMOTHERAPY ON CHILDREN WITH POSTERIOR FOSSA BRAIN TUMORS

Abstract BACKGROUND Few neuroimaging studies of children with brain tumors treated with chemotherapy without radiation exist, and the neuropsychological effects of chemotherapy remain unclear. We aimed to differentiate the effects of surgery and chemotherapy on brain microstructure and cognition. METHODS Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery alone; 11 treated with surgery + chemotherapy), and 21 sibling controls (n= 49) underwent diffusion tensor imaging (DTI) and neuropsychological assessment a mean of 4.5 (surgery group) to 9 years (surgery + chemotherapy group) after treatment. Psychometric measures focused on general intelligence, executive functions, processing speed, learning and memory, and social-emotional functioning. Age at diagnosis and time since diagnosis were covariates in the analyses. Group differences in DTI findings and psychometric scores, and correlations between psychometric scores and DTI results were examined. RESULTS Mean fractional anisotropy (FA) in the prefrontal cortex, white matter tracts, hippocampus, putamen, globus pallidus, thalamus, and pons were significantly (z≥ 2SD) lower in children treated with surgery + chemotherapy compared to those treated with surgery alone. In neuropsychological evaluation, the patient groups differed only in receptive vocabulary (p= 0.05), with children treated with surgery + chemotherapy scoring lower. Both patient groups scored lower than healthy sibling controls on measures of visuoconstructional reasoning (p= 0.02) and delayed visual (p= 0.02) and spatial memory (p= 0.01). Lower FA in the uncinate fasciculus and higher FA in the right thalamus associated with higher scores on general intelligence (p= 0.003, p= 0.002), and higher FA in the right thalamus associated with higher scores on spatial learning (p= 0.01) and memory (p= 0.01) in children treated with surgery + chemotherapy. CONCLUSIONS Chemotherapy is associated with injury to the microstructure of white and gray matter and neuropsychological deficits not seen in children with posterior fossa tumors treated with surgery alone.

Developmental Exposure to Air Pollution, Cigarettes, and Lead: Implications for Brain Aging

Brain development is impaired by maternal exposure to airborne toxins from ambient air pollution, cigarette smoke, and lead. Shared postnatal consequences include gray matter deficits and abnormal behaviors as well as elevated blood pressure. These unexpectedly broad convergences have implications for later life brain health because these same airborne toxins accelerate brain aging. Gene-environment interactions are shown for ApoE alleles that influence the risk of Alzheimer disease. The multigenerational trace of these toxins extends before fertilization because egg cells are formed in the grandmaternal uterus. The lineage and sex-specific effects of grandmaternal exposure to lead and cigarettes indicate epigenetic processes of relevance to future generations from our current and recent exposure to airborne toxins.

Partial-volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia.

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial‐volume‐based over probabilistic‐based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex‐matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel‐wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub‐region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.

Gray Matter Deficits and Dysfunction in the Insula Among Individuals With Intermittent Explosive Disorder.

Although numerous neuroimaging studies have evaluated the characteristics of intermittent explosive disorder (IED), studies on the structural alterations and focal dysfunction in the brain in this condition are limited. This study aimed to identify gray matter deficits and functional alterations in individuals with IED using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) analyses. Fifteen men with IED and 15 age- and sex-matched healthy controls participated in this study. Gray matter volume and brain activation while viewing the anger-inducing films were measured using 7T MRI. VBM results indicated that individuals with IED had significantly reduced gray matter volume in the insula, amygdala, and orbitofrontal area, relative to controls. Gray matter volume in the left insula was negatively correlated with composite aggression scores. fMRI results demonstrated that relative to healthy controls, individuals with IED showed greater activation in the insula, putamen, anterior cingulate cortex, and amygdala during anger processing. Left insular activity was positively correlated with composite aggression scores. Collectively, these findings suggest that structural and functional alterations in the left insula are linked to IED; this provides insight into the neural mechanisms underlying IED.