Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms.

BackgroundAlthough differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures.MethodsWe performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM).ResultsControlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes.ConclusionGray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism

Predicting academic career outcomes by predoctoral publication record

Background For students entering a science PhD program, a tenure-track faculty research position is often perceived as the ideal long-term goal. A relatively small percentage of individuals ultimately achieve this goal, however, with the vast majority of PhD recipients ultimately finding employment in industry or government positions. Given the disparity between academic career ambitions and outcomes, it is useful to understand factors that may predict those outcomes. Toward this goal, the current study examined employment status of PhD graduates from biomedical sciences programs at the University of Colorado Anschutz Medical Campus (CU AMC) and related this to metrics of predoctoral publication records, as well as to other potentially important factors, such as sex and time-since-degree, to determine if these measures could predict career outcomes. Methods Demographic information (name, PhD program, graduation date, sex) of CU AMC biomedical sciences PhD graduates between 2000 and 2015 was obtained from University records. Career outcomes (academic faculty vs. non-faculty) and predoctoral publication records (number and impact factors of first-author and non-first-author publications) were obtained via publicly available information. Relationships between predoctoral publication record and career outcomes were investigated by (a) comparing faculty vs. non-faculty publication metrics, using t-tests, and (b) investigating the ability of predoctoral publication record, sex, and time-since-degree to predict career outcomes, using logistic regression. Results Significant faculty vs. non-faculty differences were observed in months since graduation (p < 0.001), first-author publication number (p = 0.001), average first-author impact factor (p = 0.006), and highest first-author impact factor (p = 0.004). With sex and months since graduation as predictors of career outcome, the logistic regression model was significant (p < 0.001), with both being male and having more months since graduation predicting career status. First-author related publication metrics (number of publications, average impact factor, highest impact factor) all significantly improved model fit (χ2 < 0.05 for all) and were all significant predictors of faculty status (p < 0.05 for all). Non-first-author publication metrics did not significantly improve model fit or predict faculty status. Discussion Results suggest that while sex and months since graduation also predict career outcomes, a strong predoctoral first-author publication record may increase likelihood of obtaining an academic faculty research position. Compared to non-faculty, individuals employed in faculty positions produced more predoctoral first-author publications, with these being in journals with higher impact factors. Furthermore, first-author publication record, sex, and months since graduation were significant predictors of faculty status

Functional imaging of hippocampal dysfunction among persons with Alzheimer’s disease: a proof-of-concept study

Cholinergic deficits are an early and functionally significant manifestation of Alzheimer’s disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed

Effects of dietary protein and fiber at breakfast on appetite, ad libitum energy intake at lunch, and neural responses to visual food stimuli in overweight adults

Increasing either protein or fiber at mealtimes has relatively modest effects on ingestive behavior. Whether protein and fiber have additive or interactive effects on ingestive behavior is not known. Fifteen overweight adults (5 female, 10 male; BMI: 27.1 ± 0.2 kg/m²; aged 26 ± 1 year) consumed four breakfast meals in a randomized crossover manner (normal protein (12 g) + normal fiber (2 g), normal protein (12 g) + high fiber (8 g), high protein (25 g) + normal fiber (2 g), high protein (25 g) + high fiber (8 g)). The amount of protein and fiber consumed at breakfast did not influence postprandial appetite or ad libitum energy intake at lunch. In the fasting-state, visual food stimuli elicited significant responses in the bilateral insula and amygdala and left orbitofrontal cortex. Contrary to our hypotheses, postprandial right insula responses were lower after consuming normal protein vs. high protein breakfasts. Postprandial responses in other a priori brain regions were not significantly influenced by protein or fiber intake at breakfast. In conclusion, these data do not support increasing dietary protein and fiber at breakfast as effective strategies for modulating neural reward processing and acute ingestive behavior in overweight adults.R01 MH102224 - NIMH NIH HHS; UL1 TR001108 - NCATS NIH HHS; UL1TR001108 - NCATS NIH HH

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies

Enhancing the Detection of BOLD Signal in fMRI by Reducing the Partial Volume Effect

Purpose. To investigate the advantages of reducing the partial volume effect (PVE) to enhance the detection of the BOLD signal in fMRI. Methods. A linear phase term was added in k-space to obtain half-voxel shifting of 64 × 64 T2*-weighted echo-planar images. Three sets of image data shifted in the x, y, and diagonal direction, respectively, are combined with the original 64 × 64 data to form the 128 × 128 voxel-shifted interpolated data. Results. A simulation of a synthetic fMRI dataset shows that the voxel-shifted interpolation (VSI) can increase the t-score up to 50% in single-voxel activations. An fMRI study (n=7) demonstrates that 20.4% of the interpolated voxels have higher t-scores than their nearest neighboring voxels in the original maps. The average increase of the t-score in these interpolated voxels is 13.3%. Conclusion. VSI yields increased sensitivity in detecting voxel-size BOLD activations, improved spatial accuracy of activated regions, and improved detection of the peak BOLD signal of an activated region. VSI can potentially be used as an alternative to the high-resolution fMRI studies in which reduction in SNR and increase in imaging time become prohibitive

Propensity to obesity impacts the neuronal response to energy imbalance

The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on self-identification, BMI, and personal/family weight history. 25 OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as compared to eucaloric (EU) conditions in a randomized crossover design. Each study phase included a 3 day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test day. On the test day fMRI was performed in the acute fed stated (30 minutes after a test meal) while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 minutes after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex, parahippocampus, precuneus, cingulate and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior prefrontal cortex, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity

Functional imaging of hippocampal dysfunction among persons with Alzheimer&amp;rsquo;s disease: a proof-of-concept study

David B Arciniegas1,2, Jason R Tregellas1,3, Donald C Rojas1, Burlleen Hewitt1, C Alan Anderson1,2,41Neurobehavioral Disorders Program, Department of Psychiatry, 2Behavioral Neurology Section, University of Colorado Denver, Aurora, CO, USA; 3Research Service, 4Neurology Service, Denver Veterans Affairs Medical Denver, Denver, CO, USAAbstract: Cholinergic deficits are an early and functionally significant manifestation of Alzheimer&amp;rsquo;s disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed.Keywords: Alzheimer&amp;rsquo;s disease, hippocampus, acetylcholine, functional magnetic resonance imagin