Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.

Objective Delirium duration is predictive of long-term cognitive impairment (LTCI) in Intensive Care Unit (ICU) survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and LTCI, we conducted this exploratory investigation of the associations between delirium duration, brain volumes and LTCI. Design, Setting, and Patients A prospective cohort of medical and surgical ICU survivors with respiratory failure or shock. Measurements Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and three-month follow-up. Delirium was evaluated using the Confusion Assessment Method for the ICU; cognitive outcomes were tested at three- and twelve-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results A total of 47 patients completed the MRI protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio (VBR) at hospital discharge [0.76, 95% confidence intervals (CI) (0.10, 1.41); p=0.03] and at 3-month follow-up [0.62 (0.02, 1.21), p=0.05]. Longer duration of delirium was associated with smaller superior frontal lobe [−2.11 cm3 (−3.89, −0.32); p=0.03] and hippocampal volumes at discharge [−0.58 cm3 (−0.85, −0.31), p<0.001] – regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher VBR) at three months was associated with worse cognitive performances at twelve months [lower RBANS battery score −11.17 (−21.12, −1.22), p=0.04]. Smaller superior frontal lobes, thalamus, and cerebellar volumes at three months were associated with worse executive functioning and visual attention at twelve months. Conclusions These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to three months after discharge, and that smaller brain volumes are associated with LTCI up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Objective Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment (LTCI) in Intensive Care Unit (ICU) survivors. Relationships between (a) delirium duration and brain white matter integrity, and (b) between white matter integrity and LTCI are poorly understood and could be explored using Magnetic Resonance Imaging (MRI). Design, Setting, Patients A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging and cognitive testing in ICU survivors. Measurements Delirium was evaluated with the Confusion Assessment Method for the ICU (CAM-ICU) and cognitive outcomes were tested at 3 and 12-month follow-up. Following the ICU stay, Fractional Anisotropy (FA), a measure of white matter integrity, was calculated quantitatively using Diffusion Tensor Imaging (DTI) with a 3-Tesla MRI scanner at hospital discharge and three-month follow-up. We examined associations between (a) delirium duration and FA and (b) between FA and cognitive outcomes using linear regression adjusted for age and sepsis. Results A total of 47 patients with median age of 50 years completed the DTI-MRI protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower FA (i.e. reduced FA=white matter disruption) in the genu (−0.02; p = 0.04) and splenium (−0.01; p = 0.02) of the corpus callosum and anterior limb of the internal capsule (−0.02; p = 0.01) at hospital discharge. These associations persisted at 3 months for the genu (−0.02; p= 0.02) and splenium (−0.01; p= 0.004). Lower FA in the anterior limb of internal capsule at discharge (−10.35; p= 0.05) and in genu of corpus callosum at three months (−8.81; p = 0.006) was associated with worse cognitive scores at 3 and 12 months. Conclusions In this pilot investigation, delirium duration in the ICU was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

Objective-Heightened amygdala reactivity to aversive stimuli in major depression is regarded as a core feature of the underlying physiology but individual differences in amygdala response may also arise secondary to persistent changes in limbic function during early neurodevelopment relative to stressors such as childhood trauma. We sought to determine whether heightened amygdala response is a core feature of depression or a general risk factor for psychopathology secondary to early life stress.Method-Twenty unipolar depressed patients with and without a history of significant early life trauma and 16 healthy comparison subjects underwent functional MRI in a cross-sectional study comparing neural response to sad and neutral faces.Results-We observed a robust positive correlation between physical abuse and right amygdala response. A much weaker relationship with other forms of abuse and neglect was also found, suggesting differences between abuse subtypes and amygdala response. Group differences in amygdala response suggest heightened reactivity was not characteristic of persons with depression in general but was true primarily in those with a significant history of abuse.Conclusion-These findings suggest the relationship between childhood trauma and risk for depression is mediated by heightened amygdala response but varies by abuse type. Preliminary evidence for two distinct depression phenotypes based on trauma history was also supported, consistent with differential etiology.Keywords childhood trauma; amygdala; stress sensitization; depression Major depressive disorder is a serious illness estimated to affect 13 to 14 million adults annually and approximately 16% of the U.S. population across the lifespan (Kessler et al., 2003). Furthermore, the considerable social, occupational and workplace related costs associated with impaired function are estimated in the tens of billions of dollars each year (Wang et al., 2006). Childhood maltreatment has emerged as a significant risk factor for the onset of adult depression with over 500,000 documented cases of physical and sexual abuse © 2010 Elsevier Ltd. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Sedlak et al., 2010). Despite the widely appreciated magnitude of the problem, the precise mechanism by which childhood trauma may increase the risk for depression remains unclear. NIH Public AccessExaggerated amygdala response is regarded as a core feature of the underlying physiology of unipolar depression (Price and Drevets, 2010). Imaging studies utilizing both positron emission tomography (PET)...

The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.

Background-Research on the physical and psychological late effects of treatment of childhood cancer has led to the identification of significant long-term neurocognitive deficits experienced by some survivors, particularly in the areas of memory and executive functioning. Despite indications of deficits based on cognitive assessment, the identification of specific mechanisms of neurocognitive deficits using neuroimaging techniques has yet to be adequately considered.

We used functional magnetic resonance imaging (fMRI) to explore the patterns of brain activation associated with different levels of performance in exact and approximate calculation tasks in well defined cohorts of children with mathematical calculation difficulties (MD) and typically developing controls. Both groups of children activated the same network of brain regions; however, children in the MD group had significantly increased activation in parietal, frontal, and cingulate cortices during both calculation tasks. A majority of the differences occurred in anatomical brain regions associated with cognitive resources such as executive functioning and working memory that are known to support higher level arithmetic skill but are not specific to mathematical processing. We propose that these findings are evidence that children with MD use the same types of problem solving strategies as TD children, but their weak mathematical processing system causes them to employ a more developmentally immature and less efficient form of the strategies. Keywordsarithmetic; development; mathematical skill; numerical processing; school-age; mathematical disability Some children with normal intelligence have a disability in mathematics (MD) that makes the acquisition of grade-level mathematical competencies a challenge, despite adequate instruction (Barrouillet, Fayol, & Lathuliére, 1997;Fayol, Barrouillet, & Marinthe, 1998;Geary 1990;. Children with MD use the same types of strategies as their typically developing peers (Geary 1990;Geary, Hoard, & Hamson, 1999;Geary, Hamson, & Hoard, 2000;Hanich, Jordan, Kaplan, & Dick, 2001;Jordan, Hanich, & Kaplan, 2003a;2003b). However, as early as first grade, children with MD use less mature strategies and make more calculation errors (Geary 1999;Geary, Hamson, & Hoard, 2000;Jordan et al., 2003a Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuropsychologia. Author manuscript; available in PMC 2010 October 1. , 1997). In particular, children with MD demonstrate a specific weakness in the ability to accurately and quickly retrieve mathematical facts to solve single digit arithmetic problems (Barrouillet et al., 1997; Garnette & Fleischner, 1983;Geary 1990;Hanich et al., 2001;Jordan et al., 2003a;Jordan & Montani, 1997;Temple & Sherwood, 2002). Although there have been substantial gains in the understanding of cognitive risk factors for MD at a behavioral level, its neural bases in children remain to be explained.Studies with adults provide evidence of the brain regions involved in mathematical disability ...

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