Learning an atlas of a cognitive process in its functional geometry

Proceedings of the 22nd International Conference, IPMI 2011, Kloster Irsee, Germany, July 3-8, 2011.In this paper we construct an atlas that captures functional characteristics of a cognitive process from a population of individuals. The functional connectivity is encoded in a low-dimensional embedding space derived from a diffusion process on a graph that represents correlations of fMRI time courses. The atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. The atlas is not directly coupled to the anatomical space, and can represent functional networks that are variable in their spatial distribution. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects.National Science Foundation (U.S.) (IIS/CRCNS 0904625)National Science Foundation (U.S.) (CAREER grant 0642971)National Institutes of Health (U.S.) (NCRR NAC P41- RR13218)National Institute of Biomedical Imaging and Bioengineering (U.S.) (U54-EB005149)National Institutes of Health (U.S.) (U41RR019703)National Institutes of Health (U.S.) (P01CA067165)Seventh Framework Programme (European Commission) (n◦257528 (KHRESMOI)

Joint generative model for fMRI/DWI and its application to population

Author Manuscript 2011 March 12. 13th International Conference, Beijing, China, September 20-24, 2010, Proceedings, Part IWe propose a novel probabilistic framework to merge information from DWI tractography and resting-state fMRI correlations. In particular, we model the interaction of latent anatomical and functional connectivity templates between brain regions and present an intuitive extension to population studies. We employ a mean-field approximation to fit the new model to the data. The resulting algorithm identifies differences in latent connectivity between the groups. We demonstrate our method on a study of normal controls and schizophrenia patients.National Alliance for Medical Image Computing (U.S.) (NIH NIBIBNAMICU54-EB005149)Neuroimaging Analysis Center (U.S.) (NIH NCRR NAC P41-RR13218)National Institutes of Health (U.S.) (Grant R01MH074794)National Defense Science and Engineering Graduate FellowshipNational Science Foundation (U.S.) (CAREER Grant 0642971

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD)

Background: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled. Methods: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation. Results: Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P =.132 and P =.977, respectively). Conclusions: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge

An fMRI investigation of the relationship between future imagination and cognitive flexibility

While future imagination is largely considered to be a cognitive process grounded in default mode network activity, studies have shown that future imagination recruits regions in both default mode and frontoparietal control networks. In addition, it has recently been shown that the ability to imagine the future is associated with cognitive flexibility, and that tasks requiring cognitive flexibility result in increased coupling of the default mode network with frontoparietal control and salience networks. In the current study, we investigated the neural correlates underlying the association between cognitive flexibility and future imagination in two ways. First, we experimentally varied the degree of cognitive flexibility required during future imagination by manipulating the disparateness of episodic details contributing to imagined events. To this end, participants generated episodic details (persons, locations, objects) within three social spheres; during fMRI scanning they were presented with sets of three episodic details all taken from the same social sphere (Congruent condition) or different social spheres (Incongruent condition) and required to imagine a future event involving the three details. We predicted that, relative to the Congruent condition, future simulation in the Incongruent condition would be associated with increased activity in regions of the default mode, frontoparietal and salience networks. Second, we hypothesized that individual differences in cognitive flexibility, as measured by performance on the Alternate Uses Task, would correspond to individual differences in the brain regions recruited during future imagination. A task partial least squares (PLS) analysis showed that the Incongruent condition resulted in an increase in activity in regions in salience networks (e.g. the insula) but, contrary to our prediction, reduced activity in many regions of the default mode network (including the hippocampus). A subsequent functional connectivity (within-subject seed PLS) analysis showed that the insula exhibited increased coupling with default mode regions during the Incongruent condition. Finally, a behavioral PLS analysis showed that individual differences in cognitive flexibility were associated with differences in activity in a number of regions from frontoparietal, salience and default-mode networks during both future imagination conditions, further highlighting that the cognitive flexibility underlying future imagination is grounded in the complex interaction of regions in these networks

Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study.

16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV. Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results. The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Opportunities and limitations of intrinsic functional connectivity MRI

10.1038/nn.3423Nature Neuroscience167832-837NANE

The organization of the human striatum estimated by intrinsic functional connectivity

10.1152/jn.00270.2012Journal of Neurophysiology10882242-2263JONE