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Background: Cortical atrophy is common in early relapsing-remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms., Objectives: To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression., Methods: RRMS patients (n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls (n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group., Results: We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume., Conclusions: We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS., (© The Author(s), 2014.)

Background: Maternal opioid and polysubstance use during pregnancy is associated with an increased risk of child neurocognitive and visual problems and neuroanatomical differences. We hypothesized that, in contrast to findings from a previous study of children born to mothers not detoxified, children born to detoxified mothers would not show gross neuroanatomical and neurocognitive differences., Methods: Mothers with opioid and polysusbstance abuse problems and their infants (n = 11 + 12) were recruited from residential treatment institutions. Comparison mothers and infants (n = 12 + 12) were recruited from child health centers. The studies were approved by the Regional Committee of Medical Research Ethics. Children had magnetic resonance imaging scanning, neurocognitive, and visual acuity testing at 4.5 years. Neuroanatomical, cognitive, and visual acuity characteristics were compared across groups by analysis of variance and general linear models., Results: There were no significant differences across groups in neuroanatomical volumes, or cortical thickness, area, or volume. There were no differences in general neurocognitive functioning, but significantly lower left eye visual acuity, and a trend toward lower binocular visual acuity, in the drug-exposed relative to the comparison group., Conclusions: The present study does not demonstrate gross differences relative to a comparison group in neuroanatomical and general neurocognitive characteristics of children born to mothers with opioid and polysubstance abuse who were detoxified during pregnancy. However, visual acuity was significantly lower in the drug-exposed group, requiring attention. There is a pressing need for additional and larger studies of long-term and specific child outcomes in this at-risk group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Extrauterine growth restriction is common among very low birth weight infants (VLBW, BW <1,500 g). Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment., Objectives: We compared an enhanced postnatal nutrient supply to a standard supply and evaluated the effects on growth velocity, head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging (DTI). We hypothesized increased growth velocity, head circumference growth and decreased mean diffusivity (MD) in cerebral white matter (WM) areas, suggesting improved cerebral maturation among infants on the enhanced nutrient supply., Methods: In this randomized controlled trial, infants on the enhanced nutrient supply received increased amounts of energy, protein, fat, essential fatty acids and vitamin A until discharge. DTI was performed close to term equivalent age. Outcomes were growth velocity, head circumference growth and WM mean diffusivity., Results: Among the 50 included infants, 14 in the intervention group and 11 controls underwent a successful DTI. Infants on the enhanced diet achieved improved growth velocity (16.5 vs. 13.8 g/kg/day, p = 0.01) and increased head circumference (Δz score: 0.24 vs. -0.12, p = 0.15). A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi (1.19 × 10(-3) vs. 1.24 × 10(-3) mm(2)/s, p = 0.04, adjusted for age when scanned)., Conclusions: Enhanced nutrient supply to VLBW infants is associated with improved growth velocity, increased head circumference growth and decreased regional WM mean diffusivity, suggesting improved maturation of cerebral connective tracts., (© 2014 S. Karger AG, Basel.)

In a prospective longitudinal study, we investigated the outcomes of children born to mothers clinically referred for mental health problems during pregnancy (risk group, n = 17) relative to a control group (n = 31). Child cognitive functioning, and for subgroups (n = 10 + 17), brain morphometry as derived from Magnetic resonance imaging (MRI), was measured at 4½ years. Cognitive data included abstract visuospatial reasoning/problem solving and verbal scores. Subcortical regions of interest included the amygdala, accumbens area, hippocampus, caudate and putamen, chosen because their development seems potentially sensitive to an adverse intrauterine milieu and environmental experiences, and also due to their implication in cognitive and emotional processes. The risk group exhibited poorer abstract reasoning scores than the control group. No differences were found for verbal scores. MRI revealed smaller putamen volume in children in the risk group. Irrespective of group, putamen volume was positively related to visuospatial reasoning performance. Our results suggest that maternal psychopathology may be associated with child putamen development, nonverbal reasoning and problem solving skills.

It is well established that human brain white matter structure changes with aging, but the timescale and spatial distribution of this change remain uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that, after a period of relative stability during adulthood, there is an accelerated decline in anisotropy and increase in diffusivity values during senescence; and, spatially, results have been discussed within the context of several anatomical frameworks. However, inferring trajectories of change from cross-sectional data can be challenging; and, as yet, there have been no longitudinal reports of the timescale and spatial distribution of age-related white matter change in healthy adults across the adult lifespan. In a longitudinal DTI study of 203 adults between 20 and 84 years of age, we used tract-based spatial statistics to characterize the pattern of annual change in fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity and examined whether there was an acceleration of change with age. We found extensive and overlapping significant annual decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were consistent with inferior-to-superior gradients of lesser-to-greater vulnerability. Annual change increased with age, particularly within superior regions, with age-related decline estimated to begin in the fifth decade. Charting white matter microstructural changes in healthy aging provides essential context to clinical studies, and future studies should compare age trajectories between healthy participants and at-risk populations and also explore the relationship between DTI rates of change and cognitive decline., (Copyright © 2014 the authors 0270-6474/14/3415425-12$15.00/0.)

The hippocampus supports several important cognitive functions known to undergo substantial development during childhood and adolescence, for example, encoding and consolidation of vivid personal memories. However, diverging developmental effects on hippocampal volume have been observed across studies. It is possible that the inconsistent findings may attribute to varying developmental processes and functions related to different hippocampal subregions. Most studies to date have measured global hippocampal volume. We aimed to explore early hippocampal development both globally and regionally within subfields. Using cross-sectional 1.5 T magnetic resonance imaging data from 244 healthy participants aged 4-22 years, we performed automated hippocampal segmentation of seven subfield volumes; cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG), presubiculum, subiculum, fimbria, and hippocampal fissure. For validation purposes, seven subjects were scanned at both 1.5 and 3 T, and all subfields except fimbria showed strong correlations across field strengths. Effects of age, left and right hemisphere, sex and their interactions were explored. Nonparametric local smoothing models (smoothing spline) were used to depict age-trajectories. Results suggested nonlinear age functions for most subfields where volume increases until 13-15 years, followed by little age-related changes during adolescence. Further, the results showed greater right than left hippocampal volumes that seemed to be augmenting in older age. Sex differences were also found for subfields; CA2/3, CA4/DG, presubiculum, subiculum, and CA1, mainly driven by participants under 13 years. These results provide a detailed characterization of hippocampal subfield development from early childhood., (Copyright © 2014 Wiley Periodicals, Inc.)

The CNS white matter makes up about half of the human brain, and with advances in human imaging it is increasingly becoming clear that changes in the white matter play a major role in shaping human behavior and learning. However, the mechanisms underlying these white matter changes remain poorly understood. Within this special issue of Neuroscience on white matter, recent advances in our knowledge of the function of white matter, from the molecular level to human imaging, are reviewed. Collaboration between fields is essential to understand the function of the white matter, but due to differences in methods and field-specific 'language', communication is often hindered. In this review, we try to address this hindrance by introducing the methods and providing a basic background to myelin biology and human imaging as a prelude to the other reviews within this special issue., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To examine the relationship between sleep quality and cortical and hippocampal volume and atrophy within a community-based sample, explore the influence of age on results, and assess the possible confounding effects of physical activity levels, body mass index (BMI), and blood pressure., Methods: In 147 community-dwelling adults (92 female; age 53.9 ± 15.5 years), sleep quality was measured using the Pittsburgh Sleep Quality Index and correlated with cross-sectional measures of volume and longitudinal measures of atrophy derived from MRI scans separated by an average of 3.5 years. Exploratory post hoc analysis compared correlations between different age groups and included physical activity, BMI, and blood pressure as additional covariates., Results: Poor sleep quality was associated with reduced volume within the right superior frontal cortex in cross-sectional analyses, and an increased rate of atrophy within widespread frontal, temporal, and parietal regions in longitudinal analyses. Results were largely driven by correlations within adults over the age of 60, and could not be explained by variation in physical activity, BMI, or blood pressure. Sleep quality was not associated with hippocampal volume or atrophy., Conclusions: We found that longitudinal measures of cortical atrophy were widely correlated with sleep quality. Poor sleep quality may be a cause or a consequence of brain atrophy, and future studies examining the effect of interventions that improve sleep quality on rates of atrophy may hold key insights into the direction of this relationship., (© 2014 American Academy of Neurology.)

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span., (Copyright © 2014 the authors 0270-6474/14/348488-11$15.00/0.)

What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Changes in brain structure and activity as well as cognitive function are commonly seen in aging. However, it is not known when aging of brain and cognition starts, and how much of the changes observed in seemingly healthy older adults that can be ascribed to incipient neurodegenerative disease. Recent research has yielded evidence that the borders between development and aging sometimes can be fuzzy, as can the borders between dementing disease and normal age changes. In this review, we argue that many factors affecting cognitive decline and dementia represents quantitative rather than qualitative differences in characteristics that commonly exist in the population. Further, factors known to affect brain and cognition in aging will often do so through a life-long accumulation of impact, and does not need to be specific to aging. And finally, a host of environmental and genetic factors and their interplay determine optimal aging, leaving room for potential for environmental interventions to affect the outcome of the aging process. Together, we argue that these factors call for a dimensional rather than categorical, lifespan rather than aging, and multidimensional systems-vulnerability rather than simple "hypothetical biomarker" model of age-associated cognitive decline and dementia. This has implications for how we should view lifespan trajectories of change in brain and cognitive function, and how we can study, prevent, diagnose and treat age-associated cognitive deficits., (© 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

We hypothesized that higher levels of omega-3 fatty acids, vitamin D, and physical activity relate to cortical sparing, whereas higher levels of cholesterol, systolic blood pressure, and body mass index (BMI) relate to increased atrophy in the adult lifespan. Longitudinal measures of cortical thickness were derived from magnetic resonance imaging scans acquired (mean interval 3.6 years) from 203 healthy persons aged 23-87 years. At follow-up, measures of BMI, blood pressure, and physical activity were obtained. Blood levels of docosahexaenoic acid, eicosapentaenoic acid, vitamin D, and cholesterol were measured in a subsample (n = 92). Effects were tested in cortical surface-based analyses, with sex, age, follow-up interval, and the interactions between each included as covariates. Higher levels of docosahexaenoic acid, vitamin D, and physical activity related to cortical sparing. Higher cholesterol and BMI related to increased cortical thinning. Effects were independent, did not interact with age, and the cholesterol effect was restricted to males. Eicosapentaenoic acid and blood pressure showed no effects. The observed effects show promise for potential factors to reduce cortical atrophy in normal aging., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ(1-42) levels, and apolipoprotein ε4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.

Purpose of Review: Thorough knowledge of normal neural foundations for cognitive behavioral development is fundamental to understand the mechanisms of both neurodevelopmental disorders and normal adaptation. This review aims at identifying the trends in MRI studies published within the last 18 months illuminating maturational structural brain foundations for normal cognitive behavioral development., Recent Findings: Development is coordinated within neurocognitive systems, with predictable functional correlates. There is great individual variability within the normal range. Relationships between brain and cognitive variance at any given age are moderate, and appear to be of a complex and dynamic nature. Importantly, current studies point to a dimensional component to cognitive and behavioral psychopathology in which differences among healthy and clinical developmental groups exist along a continuum. Finally, factors influencing and detectable in early development are likely to have lifespan consequences., Summary: Brain development is highly coordinated, but the normal individual variation at any given age is substantial. Relationships between brain and cognitive measures are typically moderate and may fluctuate with age. A dimensional component to neural foundations for multiple developmental disorders makes the study of normal individual brain differences in development even more important to understand both normal and clinical cognitive behavioral outcomes throughout life.

Background: Magnetic resonance imaging (MRI) has brought about advances in the fields of brain plasticity and lifespan brain change, that might be of special interest for cognitive rehabilitation research and, eventually, in clinical practice. Parallel, intensive cognitive training studies show promising results for the prospect of retraining some of the impaired functioning following acquired brain injury., Objectives: However, cognitive training research is largely performed without concurrent assessments of brain structural change and reorganization, which could have addressed possible mechanisms of training-related neuroplasticity., Methods: Criticism of cognitive training studies is often focused on lack of ecologically valid, daily-living assessments of treatment effect, and on whether the applied cognitive measures overlap too much with the training exercises. Yet, the present paper takes another point of view, where the relevance of recent MRI research of brain plasticity to the field of cognitive rehabilitation is examined., Results: Arguably, treatment ought to be measured at the same level of the International Classification of Functioning, Disability and Health model, as it is targeting. In the case of cognitive training that will be the "body structure" and "body function" levels., Conclusions: MRI has shown promise to detect macro- and microstructural activity-related changes in the brain following intensive training.

The hippocampus is an anatomically and functionally heterogeneous structure, but longitudinal studies of its regional development are scarce and it is not known whether protracted maturation of the hippocampus in adolescence is related to memory development. First, we investigated hippocampal subfield development using 170 longitudinally acquired brain magnetic resonance imaging scans from 85 participants aged 8-21 years. Hippocampal subfield volumes were estimated by the use of automated segmentation of 7 subfields, including the cornu ammonis (CA) sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change was quantified using a nonlinear registration procedure. Second, associations between subfield volumes and change and verbal learning/memory across multiple retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized that short and intermediate memory would be more closely related to CA2-3/CA4-DG and extended, remote memory to CA1. Change rates were significantly different across hippocampal subfields, but nearly all subfields showed significant volume decreases over time throughout adolescence. Several subfield volumes were larger in the right hemisphere and in males, while for change rates there were no hemisphere or sex differences. Partly in support of the hypotheses, greater volume of CA1 and CA2-3 was related to recall and retention after an extended delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning. This suggests continued regional development of the hippocampus across adolescence and that volume and volume change in specific subfields differentially predict verbal learning and memory over different retention intervals, but future high-resolution studies are called for., (© 2014 S. Karger AG, Basel.)

There is growing documentation that infants exposed to opioids and poly-substances prenatally have an increased risk of aberrant development. In Norway, there are several in-patient clinics that specialize in medically supervised detoxification for pregnant women with substance dependence in a therapeutic setting. Because there is virtually no documentation on the perinatal outcome of the infants born to mothers receiving such treatment, this study aims to investigate the perinatal outcome of children born to mothers with opioid and poly-substance dependence detoxified in a residential setting during pregnancy compared with infants born to women with substance dependence at a time when no such treatment was available. Pregnant women from two time cohorts were followed from pregnancy to birth. Birth weight, head circumference, gestational age, and neonatal abstinence syndrome (NAS) were measured in infants born to mothers detoxified in a residential setting during pregnancy and compared with infants born to mothers receiving no treatment. Both study groups had concurrent comparison groups. Infants born to mothers in residential detoxification treatment experience less prenatal drug exposure and show better perinatal outcomes on gestational age and head circumference, as well as no NAS, compared to the infants in the earlier cohort whose mothers did not receive residential treatment. No miscarriages, complications, or morbidities were associated with residential detoxification treatment. Detoxification in residential treatment can be a preferred treatment form for many pregnant women struggling with drug abuse problems and should possibly be applied to a larger extent to ensure the best possible perinatal outcome for these children.

Cerebral myelin maturation and aging-related degradation constitute fundamental features of human brain integrity and functioning. Although mostly studied in the white matter, the cerebral cortex contains significant amounts of myelinated axons. However, how intracortical myelin content evolves during development, decays in aging, and links with cognition remain poorly understood. Several studies have shown the potential of mapping myelin in the cortex by use of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging signal intensity, which show inverse sensitivity to myelin. Here, we characterized cortical myelin in 339 participants 8-83 years of age using a recently introduced T1w/T2w ratio myelin mapping technique and mean diffusivity (MD) from diffusion tensor imaging. To test for cognitive correlates, we used intraindividual variability (IIV) in performance during a speeded task, a measure recently associated with white matter integrity. The results showed that intracortical myelin maturation was ongoing until the late 30s, followed by 20 relative stable years before declining from the late 50s. For MD, U-shaped paths showing similar patterns were observed, but with fewer maturational effects in some regions. IIV was correlated with both T1w/T2w ratio and MD, mainly indicating that the higher degree of intracortical myelin is associated with greater performance stability. The relations were more prominent with advancing age, suggesting that aging-related cortical demyelination contributes to increased IIV. The T1w/T2w ratio myelin-mapping technique thus seems sensitive to intracortical myelin content in normal development and aging, relates to cognitive functioning, and might constitute an important future tool in mapping normal and clinical brain changes.

Brain morphometry measures derived from magnetic resonance imaging (MRI) are important biomarkers for Alzheimer's disease (AD). The objective of the present study was to test whether we could improve morphometry-based detection and prediction of disease state by use of white matter/gray matter (WM/GM) signal intensity contrast obtained from conventional MRI scans. We hypothesized that including WM/GM contrast change along with measures of atrophy in the entorhinal cortex and the hippocampi would yield better classification of AD patients, and more accurate prediction of early disease progression. T1 -weighted MRI scans from two sessions approximately 2 years apart from 78 participants with AD (Clinical Dementia Rating (CDR) = 0.5-2) and 71 age-matched controls were used to calculate annual change rates. Results showed that WM/GM contrast decay was larger in AD compared with controls in the medial temporal lobes. For the discrimination between AD and controls, entorhinal WM/GM contrast decay contributed significantly when included together with decrease in entorhinal cortical thickness and hippocampal volume, and increased the area under the curve to 0.79 compared with 0.75 when using the two morphometric variables only. Independent effects of WM/GM contrast decay and improved classification were also observed for the CDR-based subgroups, including participants converting from either a non-AD status to very mild AD, or from very mild to mild AD. Thus, WM/GM contrast decay increased diagnostic accuracy beyond what was obtained by well-validated morphometric measures alone. The findings suggest that signal intensity properties constitute a sensitive biomarker for cerebral degeneration in AD., (Copyright © 2012 Wiley Periodicals, Inc.)

Older adults exhibit global reductions in cortical surface area, but little is known about the regional patterns of reductions or how these relate to other measures of brain structure. This knowledge is critical to understanding the dynamic relationship between different macrostructural properties of the cortex throughout adult life. Here, cortical arealization, local gyrification index (LGI), and cortical thickness were measured vertex wise across the brain surface in 322 healthy adults (20-85 years), with the aims of 1) characterizing age patterns of the three separate cortical measures and 2) testing the age-independent relationships among cortical surface area, gyrification, and thickness. Surface area showed strong age-related decreases, particularly pronounced in dorsomedial prefrontal, lateral temporal, and fusiform cortices, independently of total white matter volume. LGI decreased with age independently of regional surface area, with strongest effects laterally, extending from the angular gyrus in all directions. As expected, regional surface area and LGI were positively related. However, both measures correlated negatively with thickness, indicating increasing local arealization and gyrification with decreasing cortical thickness. We suggest that this pattern of regional "cortical stretching" reflects the well-established phylogenetic principle of maximizing surface area and gyrification rather than increase thickness to facilitate brain connectivity and functional development.

Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but this decrease occurred proportionally later in the chimpanzee lifespan than in humans. Diffusion MRI revealed widespread age-related decreases in fractional anisotropy and increases in radial diffusivity in chimpanzees and macaques. However, both the fractional anisotropy decline and the radial diffusivity increase started at a proportionally earlier age in humans than in chimpanzees. Thus, even though overall patterns of gray and white matter aging are similar in humans and chimpanzees, the longer lifespan of humans provides more time for white matter to deteriorate before death, with the result that some neurological effects of aging may be exacerbated in our species., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction., (Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

To realize our goals we continuously adapt our behavior according to internal or external feedback. Errors provide an important source for such feedback and elicit a scalp electrical potential referred to as the error-related negativity (ERN), which is a useful marker for studying typical and atypical development of cognitive control mechanisms involved in performance monitoring. In this review, we survey the available studies on age-related differences in the ERN in children and adolescents. The majority of the studies show that the ERN increases in strength throughout childhood and adolescence, suggesting continued maturation of the neural systems for performance monitoring, but there are still many unresolved questions. We further review recent research in adults that has provided important insights into the neural underpinnings of the ERN and performance monitoring, implicating distributed neural systems than include the dorsal anterior and posterior cingulate cortex, the lateral prefrontal cortex, insula, basal ganglia, thalamus and white matter connections between these regions. Finally, we discuss the possible roles of structural and functional maturation of these brain regions in the development of the ERN. Overall, we argue that future work should use multimodal approaches to give a better understanding of the neurocognitive development of performance monitoring., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Age-related changes in brain structure result from a complex interplay among various neurobiological processes, which may contribute to more complex trajectories than what can be described by simple linear or quadratic models. We used a nonparametric smoothing spline approach to delineate cross-sectionally estimated age trajectories of the volume of 17 neuroanatomic structures in 1100 healthy adults (18-94 years). Accelerated estimated decline in advanced age characterized some structures, for example hippocampus, but was not the norm. For most areas, 1 or 2 critical ages were identified, characterized by changes in the estimated rate of change. One-year follow-up data from 142 healthy older adults (60-91 years) confirmed the existence of estimated change from the cross-sectional analyses for all areas except 1 (caudate). The cross-sectional and the longitudinal analyses agreed well on the rank order of age effects on specific brain structures (Spearman ρ = 0.91). The main conclusions are that most brain structures do not follow a simple path throughout adult life and that accelerated decline in high age is not the norm of healthy brain aging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Parallels between patterns of brain maturation and cognitive development have been observed repeatedly, but studies directly testing the relationships between improvements in specific cognitive functions and structural changes in the brain are lacking. Working memory development extends throughout childhood and adolescence and likely plays a central role for cognitive development in multiple domains and in several neurodevelopmental disorders. Neuroimaging, lesion, and electrophysiological studies indicate that working memory emerges from coordinated interactions of a distributed neural network in which fronto-parietal cortical regions are critical. In the current study, verbal working memory function, as indexed by performance on the Keep Track task, and volumes of brain regions were assessed at two time points in 79 healthy children and adolescents in the age range of 8-22 years. Longitudinal change in cortical and subcortical volumes was quantified by the use of Quantitative Anatomical Regional Change. Improvement in working memory was related to cortical volume reduction in bilateral prefrontal and posterior parietal regions and in regions around the central sulci. Importantly, these relationships were not explained by differences in gender, age, or intelligence level or change in intellectual abilities. Furthermore, the relationships did not interact with age and were not significantly different in children, young adolescents, and old adolescents. The results provide the first direct evidence that structural maturation of a fronto-parietal cortical network supports working memory development.

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed.

Purpose: To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls., Patients and Methods: We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls., Results: Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume., Conclusion: Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.

Alzheimer's disease (AD) has a slow onset, so it is challenging to distinguish brain changes in healthy elderly persons from incipient AD. One-year brain changes with a distinct frontotemporal pattern have been shown in older adults. However, it is not clear to what extent these changes may have been affected by undetected, early AD. To address this, we estimated 1-year atrophy by magnetic resonance imaging (MRI) in 132 healthy elderly persons who had remained free of diagnosed mild cognitive impairment or AD for at least 3 years. We found significant volumetric reductions throughout the brain. The sample was further divided into low-risk groups based on clinical, biomarker, genetic, or cognitive criteria. Although sample sizes varied, significant reductions were observed in all groups, with rates and topographical distribution of atrophy comparable to that of the full sample. Volume reductions were especially pronounced in the default mode network, closely matching the previously described frontotemporal pattern of changes in healthy aging. Atrophy in the hippocampus predicted change in memory, with no additional default mode network contributions. In conclusion, reductions in regional brain volumes can be detected over the course of 1 year even in older adults who are unlikely to be in a presymptomatic stage of AD.

Early-life development is characterized by dramatic changes, impacting lifespan function more than changes in any other period. Developmental origins of neurocognitive late-life functions are acknowledged, but detailed longitudinal magnetic resonance imaging studies of brain maturation and direct comparisons with aging are lacking. To these aims, a novel method was used to measure longitudinal volume changes in development (n=85, 8-22 years) and aging (n=142, 60-91 years). Developmental reductions exceeded 1% annually in much of the cortex, more than double to that seen in aging, with a posterior-to-anterior gradient. Cortical reductions were greater than the subcortical during development, while the opposite held in aging. The pattern of lateral cortical changes was similar across development and aging, but the pronounced medial temporal reduction in aging was not precast in development. Converging patterns of change in adolescents and elderly, particularly in the medial prefrontal areas, suggest that late developed cortices are especially vulnerable to atrophy in aging. A key question in future research will be to disentangle the neurobiological underpinnings for the differences and the similarities between brain changes in development and aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Advances in neuroimaging techniques have recently provided glimpse into the neurobiology of complex traits of human personality. Whereas some intriguing findings have connected aspects of personality to variations in brain morphology, the relations are complex and our current understanding is incomplete. Therefore, we aimed to provide a comprehensive investigation of brain-personality relations using a multimodal neuroimaging approach in a large sample comprising 265 healthy individuals. The NEO Personality Inventory was used to provide measures of core aspects of human personality, and imaging phenotypes included measures of total and regional brain volumes, regional cortical thickness and arealization, and diffusion tensor imaging indices of white matter (WM) microstructure. Neuroticism was the trait most clearly linked to brain structure. Higher neuroticism including facets reflecting anxiety, depression and vulnerability to stress was associated with smaller total brain volume, widespread decrease in WM microstructure, and smaller frontotemporal surface area. Higher scores on extraversion were associated with thinner inferior frontal gyrus, and conscientiousness was negatively associated with arealization of the temporoparietal junction. No reliable associations between brain structure and agreeableness and openness, respectively, were found. The results provide novel evidence of the associations between brain structure and variations in human personality, and corroborate previous findings of a consistent neuroanatomical basis of negative emotionality., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the relationship between (a) pathologic levels of cerebrospinal fluid (CSF) total tau as an index of the intensity of ongoing neuronal degeneration and (b) longitudinal changes in white matter (WM) integrity in patients with mild cognitive impairment (MCI)., Materials and Methods: Participants gave written informed consent, and the Norwegian committee for medical research ethics approved the study. Thirty patients with MCI and nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF total tau levels, and 16 age-matched healthy control subjects underwent diffusion-tensor imaging at baseline and after a mean follow-up of 2.6 years ± 0.54 (standard deviation), with range of 1.58-3.98 years. The effect of diagnosis (MCI vs no MCI) at baseline and CSF tau levels at fractional anisotropy (FA), mean diffusivity, radial diffusivity (D(R)), and axial diffusivity were tested with tract-based spatial statistics. Differences in WM integrity at baseline and follow-up and change over time were compared among patients with pathologic CSF total tau levels (MCI high tau), patients with normal CSF total tau levels (MCI low tau), and healthy control subjects. Linear mixed-model between-group within-subject analyses were conducted to examine differences in rate of change over time in FA and D(R)., Results: Longitudinal analysis of regional WM change revealed significant decrease in FA (P = .038) and increase in D(R) (P = .018) in the MCI high-tau group relative to control subjects. For D(R), the changes were regionally specific to the right cingulum and the right superior and inferior longitudinal fasciculi., Conclusion: Reduction in WM integrity was greater in patients with MCI who had the most intense neuronal degeneration as indexed by using CSF total tau, suggesting that these patients might represent a subgroup of MCI with more intense WM degeneration who are possibly at greater risk of developing Alzheimer disease., (RSNA, 2012)

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

People show consistent differences in their cognitive and emotional responses to environmental cues, manifesting, for example, as variability in social reward processing and novelty-seeking behavior. However, the neurobiological foundation of human temperament and personality is poorly understood. A likely hypothesis is that personality traits rely on the integrity and function of distributed neurocircuitry. In this diffusion tensor imaging (DTI) study, this hypothesis was tested by examining the associations between reward dependence (RD) and novelty seeking (NS), as measured by Cloninger's Temperament and Character Inventory, and fractional anisotropy (FA) and mean diffusivity (MD) as DTI-derived indices of white matter (WM) microstructure across the brain. The results supported the hypothesis. RD was associated with WM architecture coherence as indicated by a negative correlation between RD and FA in frontally distributed areas including pathways connecting important constituents of reward-related neurocircuitry. The associations between RD and FA could not be explained by age, sex, alcohol consumption, or trait anxiety. In contrast, no effects were observed for NS. These findings support the theory that WM fiber tract properties modulate individual differences in social reward processing.

A core brain network is engaged in remembering the past and envisioning the future. This network overlaps with the so-called default-mode network, the activity of which increases when demands for focused attention are low. Because of their shared brain substrates, an intriguing hypothesis is that default-mode activity, measured at rest, is related to performance in separate attention-focused recall and imagination tasks. However, we do not know how functional connectivity of the default-mode network is related to individual differences in reconstruction of the past and imagination of the future. Here, we show that functional connectivity of the default-mode network in children and adolescents is related to the quality of past remembering and marginally to future imagination. These results corroborate previous findings of a common neuronal substrate for memory and imagination and provide evidence suggesting that mental time travel is modulated by the task-independent functional architecture of the default-mode network in the developing brain. A further analysis showed that local cortical arealization also contributed to explain recall of the past and imagination of the future, underscoring the benefits of studying both functional and structural properties to understand the brain basis for complex human cognition.

Neuroimaging studies have become increasingly multimodal in recent years, with researchers typically acquiring several different types of MRI data and processing them along separate pipelines that provide a set of complementary windows into each subject's brain. However, few attempts have been made to integrate the various modalities in the same analysis. Linked ICA is a robust data fusion model that takes multi-modal data and characterizes inter-subject variability in terms of a set of multi-modal components. This paper examines the types of components found when running Linked ICA on a large magnetic resonance imaging (MRI) morphometric and diffusion tensor imaging (DTI) data set comprising 484 healthy subjects ranging from 8 to 85 years of age. We find several strong global features related to age, sex, and intracranial volume; in particular, one component predicts age to a high accuracy (r=0.95). Most of the remaining components describe spatially localized modes of variability in white or gray matter, with many components including both tissue types. The multimodal components tend to be located in anatomically-related brain areas, suggesting a morphological and possibly functional relationship. The local components show relationships between surface-based cortical thickness and arealization, voxel-based morphometry (VBM), and between three different DTI measures. Further, we report components related to artifacts (e.g. scanner software upgrades) which would be expected in a dataset of this size. Most of the 100 extracted components showed interpretable spatial patterns and were found to be reliable using split-half validation. This work provides novel information about normal inter-subject variability in brain structure, and demonstrates the potential of Linked ICA as a feature-extracting data fusion approach across modalities. This exploratory approach automatically generates models to explain structure in the data, and may prove especially powerful for large-scale studies, where the population variability can be explored in increased detail., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging- and training-related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract-based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI-scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10-week interval. Further, group analysis demonstrated positive effects of training on the short-term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin-related processes in WM plasticity., (Copyright © 2011 Wiley Periodicals, Inc.)

The early cerebral connective tract development of infants born to methadone-maintained mothers and comparison infants was examined using diffusion tensor imaging. Drawing on animal models, we hypothesized higher mean diffusivity in methadone-exposed infants, corresponding to the delayed or altered maturation of neural connective tracts. Thirteen methadone-exposed infants and seven comparison infants were scanned within 13-44 days after birth. Mean diffusivity was compared across groups voxelwise throughout a common white matter skeleton defined for the sample, and in probabilistically defined tracts of interest overlapping the skeleton, i.e., the superior and inferior longitudinal fasciculi. Higher mean diffusivity (P < 0.05) in methadone-exposed infants was evident in the superior longitudinal fasciculus regionally by voxelwise analysis and whole-tract analysis. These results are preliminary, given the small sample. However, all observed effects were in the hypothesized direction, with methadone-exposed infants exhibiting higher mean diffusivity, suggesting altered maturation of connective tracts. Such differences may underlie some of the increased risk for cognitive and behavioral difficulties in children born to mothers using opioids. These findings highlight the need for further assessments of the effects of prenatal methadone exposure on neural development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although some older adults experiencing memory problems have been shown to benefit from cognitive training, evidence regarding who will improve from this type of intervention is lacking. Automated hippocampal volumetry might be used to foresee treatment outcomes. We hypothesized that larger hippocampal volumes are associated with greater memory performance changes following training, and that effects are selectively related to specific hippocampal subfields. 19 memory clinic outpatients with subjective memory impairment (mean age=60.9 years) underwent MRI-scanning and then followed an eight week training scheme aimed at improving verbal memory. We assessed verbal memory before and after training, and tested whether pretraining hippocampal volumes were related to memory improvements. To delineate regional specificity, we employed a new technique enabling automated volumetry of seven hippocampal subfields - including the cornu ammonis (CA) sectors and the dentate gyrus (DG). The results showed that larger hippocampal volumes before training were related to greater verbal recall improvements. Subfield volumetry revealed specific correlations between memory improvement and pretraining volumes of the left CA2/3 and CA4/DG. Depressive symptoms further gave a unique contribution in predicting gain of the intervention, independent of hippocampal volume. The results indicated that subjects with a stronger depressive symptom load benefited more from the training. A prediction model including baseline CA2/3-volume and depressive symptoms explained 42% of the variation in recall improvement. Our results are the first to suggest that hippocampal subfield volumetry is related to intervention outcomes in older adults experiencing memory problems. Also, previous studies have tended to exclude patients with concomitant depressive symptoms and memory complaints. The present results, however, strengthen the rationale and potential for cognitive intervention in these patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

When people make mistakes in speeded cognitive tasks, their response time on the next trial will typically be slower. This is referred to as post-error slowing (PES), and is important for optimization of performance, but its exact function remains to be decided. However, although PES is relatively stable over time, we have almost no knowledge about how PES is affected by structural brain characteristics. The aim of this study was to test to what extent white matter (WM) macro- and microstructure can account for individual differences in PES. PES was calculated for 255 healthy participants who performed a modified version of the Eriksen flanker task and underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). PES was positively related to WM volume in the caudal and rostral middle and superior frontal, medial orbitofrontal gyri and pars orbitalis. DTI analyses with tract-based spatial statistics (TBSS) showed that mean diffusivity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and anterior thalamic radiation, as well as axial diffusivity in the corpus callosum, was negatively related to PES. Path analysis demonstrated that WM micro- and macrostructure were complementary in accounting for PES. It is concluded that individual differences in WM characteristics can partly explain why some people are better at adjusting their behavior in response to poor performance than others., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Neuroanatomical correlates of developmental psychopathology such as attention deficit hyperactivity and conduct disorder have been identified. The majority of studies point to lesser gray matter in psychopathology,often involving prefrontal cortices. The goal of this study was to test whether similar neural correlates exist for behavioral variance in healthy children and adolescents. A large sample (n = 106) aged 8–19 years underwent MR scanning and their parents completed the Strength and Difficulties Questionnaire. The relationships between cortical thickness and conduct problems and hyperactivity/inattention scale scores were investigated throughout the cerebrum. No associations were found between normal variance in hyperactivity/inattention and cortical thickness.Normal variance in conduct problems was associated with thinner left hemisphere prefrontal and supramarginal cortices. Relationships between conduct problems and cortical thickness interacted with age, with the greatest differences in cortical thickness seen in the younger children. These interactions were observed in the anterior cingulate,orbitofrontal, middle and superior frontal, as well as lateral and medial temporal cortices. In conclusion, the results indicate neurobiological continuity between symptoms of conduct problems within the normal range, and conduct disorder. Relationships of thinner cortices and conduct problems were primarily seen in younger children, and appeared to decrease with age, indicative of different maturational trajectories in the groups. The long-term consequences are unknown, and the results point to a need for longitudinal studies of developmental trajectories of neuroanatomical foundations of behavioral adjustment.

APOE ε4 carriers have thicker cortex in several neocortical areas than ε4 noncarriers (Espeseth T., Westlye L.T., Fjell A.M., Walhovd K.B., Rootwelt H., Reinvang I., 2008. Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E ε4. Neurobiol. Aging 29, 329-340). To investigate potential physiological and cognitive correlates of these anatomical effects structural magnetic resonance imaging (MRI) data were obtained from 20 APOE ε3 homozygotes and 20 ε4 hetero- and homozygotes, and event-related potentials (ERPs) were recorded during a selective attention task (i.e. three-stimulus oddball). Several areas in both hemispheres were thicker in ε4 carriers than in noncarriers. ε4 carriers also had lower amplitudes to distractors (P3a) and lower target detection accuracy than noncarriers. Mean thickness in cortical areas were correlated with P3a amplitudes, which in turn correlated with accuracy. Path analyses showed that APOE-related difference in accuracy was mediated by APOE-related differences in cortical thickness and P3a amplitudes. The results suggest that APOE ε4 modulates the structural integrity of critical nodes in brain attentional networks., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Huge progress has been made in unraveling the mysteries of Alzheimer's disease (AD), but we still do not understand the basic mechanisms that set off the cascade of pathological events. In May 2011, the National Institute on Aging-Alzheimer's Association published new diagnostic guidelines, expected to have huge impact on AD research and clinical practice. However, the new guidelines are already criticized for being biased in favor of a specific theory of the pathophysiological origins of AD-the amyloid cascade hypothesis. Shortly before publication of the guidelines, a hypothetical model of the dynamic biomarkers of the Alzheimer's pathological cascade was published, taking as starting point that biomarkers reflecting brain levels of amyloid become deviant long before brain atrophy, cognitive dysfunction, or clinical symptoms are manifest. This model has already attracted substantial interest and arguably represents a dominating view within human research on AD. Here we critically review the evidence for the view of amyloid as an initiating event in the pathological cascade and discuss how central assumptions of this hypothesis affect how results from contemporary human AD research are understood. Interpretations of new results are greatly impacted by researchers' view on the role of amyloid, and identical observations are sometimes taken to support radically opposing views on the amyloid hypothesis. We argue that the canonical view of the role of amyloid as the main causal factor in AD may not be correct and that evidence from recent neuroimaging studies indicates that amyloid is neither necessary nor sufficient, for the manifestation of AD-like brain atrophy.

Retention of information over extended time periods places special demands on the brain. The neural correlates of memory performance after a short delay of 30 min and a long delay of 1 week are likely partly different, but we do not know how structural maturation of the brain contributes to the differential development of these functions. This question was investigated in a sample of 107 children and adolescents aged 8-19 years. Measures used were structural magnetic resonance imaging and the Rey Complex Figure Test copy, organizational strategy, and 30-min and 1-week recall. While the amount of details copied and later recalled after both 30 min and 1 week increased with age, the relative saving over 1 week (1-week/30-min ratio score) did not increase with age. Thirty minutes recall performance was related to thinner left orbitofrontal cortex independently of age and organizational strategy measured during copy, possibly reflecting executive components of retrieval or encoding processes. In contrast, the 1-week/30-min ratio, likely reflecting consolidation of memory traces, was related to larger bilateral hippocampal volume. This indicates that differential developmental effects on memory for short and long periods of time are related to differentially developing brain structures.

Cognitive development is known to involve improvements in accuracy, capacity, and processing speed. Less is known about the role of performance consistency, and there has been virtually no empirical examination of the neural underpinnings of within-person variability in development. In a sample of 92 healthy children and adolescents aged 8-19 years, we aimed to characterize age-related changes in trial-to-trial intraindividual variability (IIV) of reaction time (RT) and to test whether IIV is related to white matter (WM) integrity as indexed by diffusion tensor imaging. IIV was quantified as the SD of correct RTs in a speeded arrow flanker task, and Tract-Based Spatial Statistics was used to test relationships with diffusion characteristics. Large age-related reductions in IIV in both simple congruent trials and more complex incongruent trials were found. Independently of sex, age, and median RT (mRT), lower IIV was associated with higher fractional anisotropy and lower overall diffusivity. Effects were seen for IIV in one or both trial types in the corticospinal tract, the left superior longitudinal fasciculus, the uncinate fasciculus, the forceps minor, and in the genu and splenium of the corpus callosum. There were no significant associations between mRT and any of the diffusion indices. The findings support the proposition that developmental reductions in IIV reflect maturation of WM connectivity and highlight the importance of considering within-person variability in theories of cognitive development and its neurobiological foundation.