Distinct Regionalization Patterns of Cortical Morphology are Associated with Cognitive Performance Across Different Domains.

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

Polygenic risk for psychiatric disorders correlates with executive function in typical development.

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.

Recruiting the ABCD sample: Design considerations and procedures.

The ABCD study is a new and ongoing project of very substantial size and scale involving 21 data acquisition sites. It aims to recruit 11,500 children and follow them for ten years with extensive assessments at multiple timepoints. To deliver on its potential to adequately describe adolescent development, it is essential that it adopt recruitment procedures that are efficient and effective and will yield a sample that reflects the nation's diversity in an epidemiologically informed manner. Here, we describe the sampling plans and recruitment procedures of this study. Participants are largely recruited through the school systems with school selection informed by gender, race and ethnicity, socioeconomic status, and urbanicity. Procedures for school selection designed to mitigate selection biases, dynamic monitoring of the accumulating sample to correct deviations from recruitment targets, and a description of the recruitment procedures designed to foster a collaborative attitude between the researchers, the schools and the local communities, are provided.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality.

While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean=55 years) male twins (complete MZ pairs=120; complete DZ pairs=84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (r(p)) and genetic (r(g)) correlations were observed between left amygdala volume and positive emotionality (r(p)=.16, p<.01; r(g)=.23, p<.05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (r(e)) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (r(g)=.34, p<.01; r(e)=-.19, p<.05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation.

Schizophrenia-risk variant rs6994992 in the neuregulin-1 gene on brain developmental trajectories in typically developing children.

The neuregulin-1 (NRG1) gene is one of the best-validated risk genes for schizophrenia, and psychotic and bipolar disorders. The rs6994992 variant in the NRG1 promoter (SNP8NRG243177) is associated with altered frontal and temporal brain macrostructures and/or altered white matter density and integrity in schizophrenic adults, as well as healthy adults and neonates. However, the ages when these changes begin and whether neuroimaging phenotypes are associated with cognitive performance are not fully understood. Therefore, we investigated the association of the rs6994992 variant on developmental trajectories of brain macro- and microstructures, and their relationship with cognitive performance. A total of 972 healthy children aged 3-20 years had the genotype available for the NRG1-rs6994992 variant, and were evaluated with magnetic resonance imaging (MRI) and neuropsychological tests. Age-by-NRG1-rs6994992 interactions and genotype effects were assessed using a general additive model regression methodology, covaried for scanner type, socioeconomic status, sex and genetic ancestry factors. Compared with the C-carriers, children with the TT-risk-alleles had subtle microscopic and macroscopic changes in brain development that emerge or reverse during adolescence, a period when many psychiatric disorders are manifested. TT-children at late adolescence showed a lower age-dependent forniceal volume and lower fractional anisotropy; however, both measures were associated with better episodic memory performance. To our knowledge, we provide the first multimodal imaging evidence that genetic variation in NRG1 is associated with age-related changes on brain development during typical childhood and adolescence, and delineated the altered patterns of development in multiple brain regions in children with the T-risk allele(s).

Genome-wide association study of shared components of reading disability and language impairment.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Reduction of edge-localized mode intensity using high-repetition-rate pellet injection in tokamak H-mode plasmas.

High repetition rate injection of deuterium pellets from the low-field side (LFS) of the DIII-D tokamak is shown to trigger high-frequency edge-localized modes (ELMs) at up to 12× the low natural ELM frequency in H-mode deuterium plasmas designed to match the ITER baseline configuration in shape, normalized beta, and input power just above the H-mode threshold. The pellet size, velocity, and injection location were chosen to limit penetration to the outer 10% of the plasma. The resulting perturbations to the plasma density and energy confinement time are thus minimal (<10%). The triggered ELMs occur at much lower normalized pedestal pressure than the natural ELMs, suggesting that the pellet injection excites a localized high-n instability. Triggered ELMs produce up to 12× lower energy and particle fluxes to the divertor, and result in a strong decrease in plasma core impurity density. These results show for the first time that shallow, LFS pellet injection can dramatically accelerate the ELM cycle and reduce ELM energy fluxes on plasma facing components, and is a viable technique for real-time control of ELMs in ITER.

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men.

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05). There were strong phenotypic correlations between self-esteem and well-being (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P < 0.001). In multivariate genetic analyses, a two-factor additive genetic and unique environmental (AE) model with well-being and self-esteem on one factor and left and right hippocampal volumes on the other factor fits the data better than Cholesky, independent pathway or common pathway models. The correlation between the two genetic factors was 0.12 (P = 0.03); the correlation between the environmental factors was 0.09 (P > 0.05). Our results indicate that largely different genetic and environmental factors underlie self-esteem and well-being on one hand and hippocampal volume on the other.

HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study.

OBJECTIVES: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). METHODS: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). RESULTS: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups). CONCLUSIONS: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

Cerebral serotonin transporter binding is inversely related to body mass index.

Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established.

Comparison of small-intestinal submucosa and expanded polytetrafluoroethylene as a vascular conduit in the presence of gram-positive contamination.

OBJECTIVE: As a vascular conduit, expanded polytetrafluoroethylene (ePTFE) is susceptible to graft infection with Gram-positive organisms. Biomaterials, such as porcine small-intestinal submucosa (SIS), have been successfully used clinically as tissue substitutes outside the vascular arena. SUMMARY BACKGROUND DATA: In the present study, we compared a small-diameter conduit of SIS to ePTFE in the presence of Gram-positive contamination to evaluate infection resistance, incorporation and remodeling, morphometry, graft patency, and neointimal hyperplasia (NH) development. METHODS: Adult male mongrel pigs were randomized to receive either SIS or ePTFE (3-cm length, 6-mm diameter) and further randomized to 1 of 3 groups: Control (no graft inoculation), Staphylococcus aureus, or mucin-producing S epidermidis (each graft inoculation with 10 colonies/mL). Pressure measurements were obtained proximal and distal to the graft to create the iliac/aorta pressure ratio. Morphometric analysis of the neointima and histopathologic examinations was performed. Other outcomes included weekly WBC counts, graft incorporation, and quantitative culture of explanted grafts. RESULTS: Eighteen animals were randomized. All grafts were patent throughout the 6-week study period. Infected SIS grafts had less NH and little change in their iliac/aorta indices compared with infected ePTFE grafts. Quantitative cultures at euthanasia demonstrated no growth in either SIS group compared with 1.7 x 10(4) colonies for ePTFE S aureus and 6 x 10(2) for ePTFE S epi (each P < 0.001). All SIS grafts were incorporated. Histology demonstrated remodeling into host artery with smooth muscle and capillary ingrowth in all SIS groups. Scanning electron micrography illustrated smooth and complete endothelialization of all SIS grafts. CONCLUSIONS: Compared with ePTFE, SIS induces host tissue remodeling, exhibits a decreased neointimal response to infection, and is resistant to bacterial colonization. SIS may provide a superior alternative to ePTFE as a vascular conduit for peripheral vascular surgery.

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Small intestinal submucosa for vascular reconstruction in the presence of gastrointestinal contamination.

INTRODUCTION: Surgical options for vascular reconstruction in a contaminated field are limited and include prosthetic reconstruction or ligation with extra-anatomic bypass. With prosthetic insertion, rates of graft infection and failures (pseudoaneurysms and thrombosis) are high. In the emergent situations, extra-anatomic bypass is time-consuming and complex, and it produces marginal long-term results. Small intestinal submucosa (SIS) is a cell-free collagen matrix derived from porcine small intestine. Preliminary studies have demonstrated its ability to be remodeled into host tissue. In this study, we compared SIS to polytetrafluoroethylene (PTFE) as a vascular patch for arterial repair in the presence of massive gastrointestinal contamination to evaluate graft patency, incorporation, infection, and aneurysm formation. METHODS: Adult mongrel pigs underwent general anesthesia with Isoflurane and were then randomized to 1 of 3 groups: control, contamination (colon puncture with stool contamination of the pelvis), or shock + contamination (40% blood volume for 1 hour, then resuscitation with shed blood and crystalloid, plus contamination). All groups then underwent a left common iliac arteriotomy and further randomized to a 1 x 3-cm patch angioplasty with either SIS or PTFE. All received cefotetan for 24 hours. All animals were sacrificed between 2 and 4 weeks, and necropsy was performed. Grafts were cultured, and microscopic analysis with hematoxylin and eosin and trichrome was performed. Outcomes included pulse quality (normal or diminished) compared with opposite side, graft infection, and pseudoaneurysm; all were determined by a blinded investigator. RESULTS: Forty animals were randomized, and 1 died of abdominal sepsis. All control animals had normal distal pulses, no pseudoaneurysms, and no patch infections. The pseudoaneurysm rate for the contaminated PTFE patches was 25% compared with 0% in the SIS group (P = 0.09). Patch infection occurred in 73% of all PTFE patches compared with 8% of SIS patches (P < 0.03). Organisms present in the infected grafts included Escherichia coli, Bacteroides species, and other Gram-negative enterics. Histopathology demonstrated the presence of neointima in both SIS and PTFE. Only SIS was completely incorporated, with infiltration of collagen fibrils and lymphocytes. CONCLUSIONS: SIS was associated with improved graft patency, less infection, complete incorporation, and no false aneurysm formation when compared with PTFE. This may be due to its ability to provide a durable scaffold for cellularization and tissue remodeling. This material may offer a superior alternative to more complex vascular reconstruction techniques in contaminated fields.

Apoptosis and necrosis in the development of acute lung injury after hemorrhagic shock.

Acute lung injury can be a complication of hemorrhagic shock. Mechanisms of injury include neutrophil-derived inflammatory products that induce necrosis within the lung. Recent data has shown apoptosis, in addition to necrosis, as a pathway leading toward acute lung injury in shock models. This study quantitates apoptotic and necrotic cells in the lung after hemorrhagic shock. Mongrel pigs (20-30 kg) under general anesthesia (with pancuronium and pentobarbital) underwent instrumentation with placement of carotid and external jugular catheters. The animals were randomized to sham hemorrhage (n = 6) and to hemorrhagic shock (n = 7). The hemorrhagic shock group then underwent hemorrhage (40-45% blood volume) to a systolic blood pressure of 40-50 mm Hg for 1 hour. The animals were then resuscitated with shed blood plus crystalloid to normalization of heart rate and blood pressure. The animals were observed under general anesthesia for 6 hours after resuscitation, then sacrificed, and lungs were harvested. Lung injury parameters including histology (H&E stain), apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL)], and myeloperioxidase activity (spectrophotometric assay) were assessed. Hemorrhagic shock induced marked loss of lung architecture, neutrophil infiltration, alveolar septal thickening, hemorrhage, and edema in H&E staining. Furthermore, MPO activity, a marker for neutrophil infiltration and activation, was more than doubled as compared to controls (44.0 vs 20.0 Grisham units activity/g). Apoptosis (cell shrinkage, membrane blebbing, apoptotic bodies) and necrosis (cellular swelling, membrane lysis) in neutrophils, macrophages, as well as in alveolar cells was demonstrated and quantified by H&E staining use. Apoptosis was confirmed and further quantified by positive TUNEL signaling via digital semiquantitative analysis, which revealed a significant increase in apoptotic cells (16.0 vs 2.5 cells/hpf, shock vs control, respectively) and necrotic cells (16.0 vs 2.0 cells/hpf, shock vs control, respectively). Acute lung injury is a complex pathophysiologic process. Apoptosis in cells (neutrophils, macrophages, alveolar cells) is induced within the lung after hemorrhagic shock. The role of apoptosis in pulmonary dysfunction after hemorrhagic shock has yet to be determined.

Staged management of giant abdominal wall defects: acute and long-term results.

INTRODUCTION: Shock resuscitation leads to visceral edema often precluding abdominal wall closure. We have developed a staged approach encompassing acute management through definitive abdominal wall reconstruction. The purpose of this report is to analyze our experience with this technique applied to the treatment of patients with open abdomen and giant abdominal wall defects. METHODS: Our management scheme for giant abdominal wall defects consists of 3 stages: stage I, absorbable mesh insertion for temporary closure (if edema quickly resolves within 3-5 days, the mesh is gradually pleated, allowing delayed fascial closure); stage II, absorbable mesh removal in patients without edema resolution (2-3 weeks after insertion to allow for granulation and fixation of viscera) and formation of the planned ventral hernia with either split thickness skin graft or full thickness skin closure over the viscera; and stage III, definitive reconstruction after 6-12 months (allowing for inflammation and dense adhesion resolution) by using the modified components separation technique. Consecutive patients from 1993 to 2001 at a single institution were evaluated. Outcomes were analyzed by management stage, with emphasis on wound related morbidity and mortality, and fistula and recurrent hernia rates. RESULTS: Two hundred seventy four patients (35 with sepsis, 239 with hemorrhagic shock) were managed. There were 212 males (77%), and mean age was 37 (range, 12-88). The average size of the defects was 20 x 30 cm. In the stage I group, 108 died (92% of all deaths) because of shock. The remaining 166 had temporary closure with polyglactin 910 woven absorbable mesh. As visceral edema resolved, bedside pleating of the absorbable mesh allowed delayed fascial closure in 37 patients (22%). In the stage II group, 9 died (8% of all deaths) from multiple organ failure associated with their underlying disease process, and 96% of the remaining 120 had split-thickness skin graft placed over the viscera. No wound related mortality occurred. There were a total of 14 fistulae (5% of total, 8% of survivors). In the stage III group, to date, 73 of the 120 have had definitive abdominal wall reconstruction using the modified components separation technique. There were no deaths. Mean follow-up was 24 months, (range 2-60). Recurrent hernias developed in 4 of these patients (5%). CONCLUSIONS: The staged management of patients with giant abdominal wall defects without the use of permanent mesh results in a safe and consistent approach for both initial and definitive management with low morbidity and no technique-related mortality. Absorbable mesh provides effective temporary abdominal wall defect coverage with a low fistula rate. Because of the low recurrent hernia rate and avoidance of permanent mesh, the components separation technique is the procedure of choice for definitive abdominal wall reconstruction.

Mitigation of tokamak disruptions using high-pressure gas injection.

High-pressure gas-jet injection of neon and argon is shown to be a simple and robust method to mitigate the deleterious effects of disruptions on the DIII-D tokamak. The gas jet penetrates to the central plasma at its sonic velocity. The deposited species dissipates >95% of the plasma by radiation and substantially reduces mechanical stresses on the vessel caused by poloidal halo currents. The gas-jet species-charge distribution can include >50% fraction neutral species which inhibits runaway electrons. The favorable scaling of this technique to burning fusion plasmas is discussed.

Effects of age on tissues and regions of the cerebrum and cerebellum.

Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to estimated volumes of: gray matter, white matter, and CSF of the cerebrum and cerebellum; gray matter, white matter, white matter abnormality, and CSF within each cerebral lobe; and gray matter of eight subcortical structures. The results were: 1) Age-related losses in the hippocampus were significantly accelerated relative to gray matter losses elsewhere in the brain. 2) Among the cerebral lobes, the frontal lobes were disproportionately affected by cortical volume loss and increased white matter abnormality. 3) Loss of cerebral and cerebellar white matter occurred later than, but was ultimately greater than, loss of gray matter. It is estimated that between the ages of 30 and 90 volume loss averages 14% in the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white matter. Separate analyses were conducted in which genetic risk associated with the Apolipoprotein E epsilon4 allele was either overrepresented or underrepresented among elderly participants. Accelerated loss of hippocampal volume was observed with both analyses and thus does not appear to be due to the presence of at-risk subjects. MR signal alterations in the tissues of older individuals pose challenges to the validity of current methods of tissue segmentation, and should be considered in the interpretation of the results.

Mapping callosal morphology and cognitive correlates: effects of heavy prenatal alcohol exposure.

BACKGROUND: Abnormalities of the corpus callosum (CC) have been documented in fetal alcohol syndrome (FAS), ranging from subtle decrements in its size to partial and even complete agenesis. Prenatal exposure to alcohol is also known to result in neurocognitive deficits. OBJECTIVE: To 1) investigate abnormalities in size, shape, and location of the CC within the brain in individuals with FAS and in those exposed to high amounts of alcohol prenatally but without FAS (PEA group); and 2) determine if there is a relationship between callosal dysmorphology and cognitive test performance. METHODS: MRI and novel surface-based image analytic methods were used. Twenty alcohol-exposed subjects (8 to 22 years) along with 21 normal controls (8 to 25 years) were studied with high-resolution MRI and measures of verbal learning and visuospatial abilities. RESULTS: In addition to callosal area reductions, most severe in the splenium, the CC is significantly displaced in patients exposed to alcohol prenatally. In the alcohol-exposed group, this structure lies more anterior and inferior in posterior regions with relatively normal localization of anterior regions. These findings are significant in the FAS group, and a similar but less severe pattern is observed in the PEA patients. The authors show that the amount of CC displacement is correlated with impairment in verbal learning ability and that CC displacement is a better predictor of verbal learning than regional CC area. The brain-behavior relationship is only significant within the alcohol-exposed group, and the effect is not solely mediated by overall impaired verbal intellectual functioning. CONCLUSIONS: These results further emphasize the vulnerability of midline brain structures to prenatal alcohol exposure.