Neuroanatomical Correlates of Bifactor Model of Internalizing Psychopathology Across The Lifespan

High rates of comorbidity between internalizing disorders and heterogeneity in the behavioral manifestations of a single disorder have made it challenging to identify biological signatures of specific mental illnesses. This may in part be due to the case-control frameworks which dominate psychopathology research, frameworks which draw stark distinctions between patients and healthy individuals despite evidence that such distinctions may not reflect the distribution of behavior across the population. To address these issues, there has been a recent emphasis on employing dimensional models of psychopathology which characterize psychopathology as arising through the interaction of behaviors that are continuously distributed throughout the general population. In the current dissertation project, we first propose a novel six-factor dimensional model of internalizing psychopathology and demonstrate that dimensions in this model show preferential associations with specific internalizing disorders. We then employ gray matter morphometry analyses to identify the degree to which individual differences in internalizing dimensions are associated with structural properties of gray matter across the brain. Finally, we evaluate which dimensions are driven by genes or the environment, as well as the degree to which relationships between these dimensions and gray matter structure result from overlapping genetic or environmental influences. Our findings suggest 1) previous dimensional models of internalizing psychopathology may be improved by including cognitive dimensions of behavior, including rumination and repetitive negative thought, 2) the brain regions associated with internalizing dimensions are more distributed than the regions identified in case-control studies while also changing with age and differing by sex, and 3) behaviors that are common across internalizing disorders are largely genetic in nature, whereas behaviors that are specific to anxiety may be influenced by shared environmental factors.</p

Whole-cortex mapping of common genetic influences on depression and a social deficits dimension

Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed. We developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU in a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS). We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters. Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal-temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified "theory of mind", "inhibit", and "pain" as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels. CU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability.</p

Individual differences in emotion-cognition interactions: Emotional valence interacts with serotonin transporter genotype to influence brain systems involved in emotional reactivity and cognitive control

The serotonin transporter gene (5-HTTLPR) influences emotional reactivity and attentional bias toward or away from emotional stimuli, and has been implicated in psychopathological states, such as depression and anxiety disorder. The short allele is associated with increased reactivity and attention toward negatively-valenced emotional information, whereas the long allele is associated with increased reactivity and attention towardpositively-valenced emotional information. The neural basis for individual differences in the ability to exert cognitive control over these bottom-up biases in emotional reactivity and attention is unknown, an issue investigated in the present study. Healthy adult participants were divided into two groups, either homozygous carriers of the 5-HTTLPR long allele or homozygous carriers of the short allele, and underwent functional magnetic resonance imaging (fMRI) while completing an Emotional Stroop-like task that varied in the congruency of task-relevant and task-irrelevant information and the emotional valence of the task-irrelevant information. Behaviorally, participants demonstrated the classic “Stroop effect” (responses were slower for incongruent than congruent trials), which did not differ by 5-HTTLPR genotype. However, fMRI results revealed that genotype influenced the degree to which neural systems were engaged depending on the valence of the conflicting task-irrelevant information. While the “Long” group recruited prefrontal control regions and superior temporal sulcus during conflict when the task-irrelevant information was positively-valenced, the “Short” group recruited these regions during conflict when the task-irrelevant information was negatively-valenced. Thus, participants successfully engaged cognitive control to overcome conflict in an emotional context using similar neural circuitry, but the engagement of this circuitry depended on emotional valence and 5-HTTLPR status. These results suggest that the interplay between emotion and cognition is modulated, in part, by a genetic polymorphism that influences serotonin neurotransmission

The Emotional Word-Emotional Face Stroop task in the ABCD study: Psychometric validation and associations with measures of cognition and psychopathology

Characterizing the interactions among attention, cognitive control, and emotion during adolescence may provide important insights into why this critical developmental period coincides with a dramatic increase in risk for psychopathology. However, it has proven challenging to develop a single neurobehavioral task that simultaneously engages and differentially measures these diverse domains. In the current study, we describe properties of performance on the Emotional Word-Emotional Face Stroop (EWEFS) task in the Adolescent Brain Cognitive Development (ABCD) Study, a task that allows researchers to concurrently measure processing speed/attentional vigilance (i.e., performance on congruent trials), inhibitory control (i.e., Stroop interference effect), and emotional information processing (i.e., difference in performance on trials with happy as compared to angry distracting faces). We first demonstrate that the task manipulations worked as designed and that Stroop performance is associated with multiple cognitive constructs derived from different measures at a prior time point. We then show that Stroop metrics tapping these three domains are preferentially associated with aspects of externalizing psychopathology and inattention. These results highlight the potential of the EWEFS task to help elucidate the longitudinal dynamics of attention, inhibitory control, and emotion across adolescent development, dynamics which may be altered by level of psychopathology

Adolescent Brain Cognitive Development (ABCD) Study Linked External Data (LED): Protocol and practices for geocoding and assignment of environmental data

Our brain is constantly shaped by our immediate environments, and while some effects are transient, some have long-term consequences. Therefore, it is critical to identify which environmental risks have evident and long-term impact on brain development. To expand our understanding of the environmental context of each child, the Adolescent Brain Cognitive Development (ABCD) Study® incorporates the use of geospatial location data to capture a range of individual, neighborhood, and state level data based on the child\u27s residential location in order to elucidate the physical environmental contexts in which today\u27s youth are growing up. We review the major considerations and types of geocoded information incorporated by the Linked External Data Environmental (LED) workgroup to expand on the built and natural environmental constructs in the existing and future ABCD Study data releases. Understanding the environmental context of each youth furthers the consortium\u27s mission to understand factors that may influence individual differences in brain development, providing the opportunity to inform public policy and health organization guidelines for child and adolescent health

Tracts originating from each of the clusters in the left hemisphere <i>K</i> = 6.

<p>Label colors (on left) match the cluster colors in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124797#pone.0124797.g002" target="_blank">Fig 2</a> (K = 6), which is reproduced at the bottom right. The color scale on brain maps represents the proportion of tract overlap across the participants, with the maps thresholded at 50%. Axial slices are shown in the left column, with slice locations marked on the sagittal slice with a blue line. Sagittal slices are shown in the right column, with slice locations marked on the axial slice with a blue line. MNI coordinates for the <i>z</i>-axis (axial slices) and <i>x</i>-axis (sagittal slices) are shown above the top row.</p

Organization of the Human Frontal Pole Revealed by Large-Scale DTI-Based Connectivity: Implications for Control of Behavior

<div><p>The goal of the current study was to examine the pattern of anatomical connectivity of the human frontal pole so as to inform theories of function of the frontal pole, perhaps one of the least understood region of the human brain. Rather than simply parcellating the frontal pole into subregions, we focused on examining the brain regions to which the frontal pole is anatomically and functionally connected. While the current findings provided support for previous work suggesting the frontal pole is connected to higher-order sensory association cortex, we found novel evidence suggesting that the frontal pole in humans is connected to posterior visual cortex. Furthermore, we propose a functional framework that incorporates these anatomical connections with existing cognitive theories of the functional organization of the frontal pole. In addition to a previously discussed medial-lateral distinction, we propose a dorsal-ventral gradient based on the information the frontal pole uses to guide behavior. We propose that dorsal regions are connected to other prefrontal regions that process goals and action plans, medial regions are connected to other brain regions that monitor action outcomes and motivate behaviors, and ventral regions connect to regions that process information about stimuli, values, and emotion. By incorporating information across these different levels of information, the frontal pole can effectively guide goal-directed behavior.</p></div

Cluster metrics.

<p>A) Variation of information metric for each <i>K</i> value and each hemisphere. Error bars represent 95% confidence intervals. B) Hierarchy index for each <i>K</i> value and each hemisphere. C) Symmetry measurement between the left and right hemispheres for each <i>K</i> value. D) Average of the standard deviation in the center-of-gravity across clusters for each <i>K</i> value.</p