Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks.
View Article and Find Full Text PDFNeuroimaging research has uncovered a multitude of neural abnormalities associated with psychopathology, but few prediction-based studies have been conducted during adolescence, and even fewer used neurobiological features that were extracted across multiple neuroimaging modalities. This gap in the literature is critical, as deriving accurate brain-based models of psychopathology is an essential step towards understanding key neural mechanisms and identifying high-risk individuals. As such, we trained adaptive tree-boosting algorithms on multimodal neuroimaging features from the Lifespan Human Connectome Developmental (HCP-D) sample that contained 956 participants between the ages of 8 to 22 years old.
View Article and Find Full Text PDFBehavioral genetic analyses have not demonstrated robust, unique, genetic correlates of hippocampal subregion volume. Genetic differentiation of hippocampal longitudinal axis subregion volume has not yet been investigated in population-based samples, although this has been demonstrated in rodent and post-mortem human tissue work. The following study is the first population-based investigation of genetic factors that contribute to gray matter volume along the hippocampal longitudinal axis.
View Article and Find Full Text PDFChromosome instability (CIN) contributes to resistance to therapies and tumor evolution. Although natural killer (NK) cells can eliminate cells with complex karyotypes, high-CIN human tumors have an immunosuppressive phenotype. To understand which CIN-associated molecular features alter immune recognition during tumor evolution, we overexpress Polo-like kinase 1 (Plk1) in a Her2 breast cancer model.
View Article and Find Full Text PDFDepression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts ( = 93), and one replication cohort ( = 180).
View Article and Find Full Text PDFAt the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level.
View Article and Find Full Text PDFStudies demonstrate that individuals with diagnoses for Major Depressive Disorder (MDD), Post-traumatic Stress Disorder (PTSD), and Schizophrenia (SCZ) may exhibit smaller hippocampal gray matter relative to otherwise healthy controls, although the effect sizes vary in each disorder. Existing work suggests that hippocampal abnormalities in each disorder may be attributable to genetic liability and/or environmental variables. The following study uses baseline data from the Adolescent Brain and Cognitive Development[Formula: see text] Study (ABCD Study[Formula: see text]) to address three open questions regarding the relationship between genetic risk for each disorder and hippocampal volume reductions: (a) whether polygenic risk scores (PGRS) for MDD, PTSD, and SCZ are related to hippocampal volume; (b) whether PGRS for MDD, PTSD, and SCZ are differentially related to specific hippocampal subregions along the longitudinal axis; and (c) whether the association between PGRS for MDD, PTSD, and SCZ and hippocampal volume is moderated by sex and/or environmental adversity.
View Article and Find Full Text PDFIntroduction: Compared to research on adults with depression, relatively little work has examined white matter microstructure differences in depression arising earlier in life. Here we tested hypotheses about disruptions to white matter structure in adolescents with current and past depression, with an a priori focus on the cingulum bundles, uncinate fasciculi, corpus collosum, and superior longitudinal fasciculus.
Methods: One hundred thirty-one children from the Preschool Depression Study were assessed using a Human Connectome Project style diffusion imaging sequence which was processed with HCP pipelines and TRACULA to generate estimates of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD).
Adverse experiences and family income in childhood have been associated with altered brain development. While there is a large body of research examining these associations, it has primarily used cross-sectional data sources and studied adverse experiences and family income in isolation. However, it is possible that low family income and adverse experiences represent dissociable and potentially interacting profiles of risk.
View Article and Find Full Text PDFThe human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.
View Article and Find Full Text PDFJ Am Acad Child Adolesc Psychiatry
November 2022
Objective: Depression and low socioeconomic status have both been associated with hippocampal volume alterations. Whether these factors interact to predict neurobehavioral outcomes has not been adequately studied. The authors investigated family income as a moderator of the relationship between depression and hippocampal volume in a longitudinal sample.
View Article and Find Full Text PDFMagnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)).
View Article and Find Full Text PDFBiol Psychiatry Cogn Neurosci Neuroimaging
January 2022
Background: Early low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood.
View Article and Find Full Text PDFMonitoring one's performance helps detect errors and adapt to prevent future mistakes. However, elevated performance monitoring is associated with increased checking behaviors and perfectionism and is characteristic of multiple psychiatric disorders. Understanding how heightened performance monitoring in early childhood relates to subsequent brain connectivity may elucidate mechanistic risk factors that influence brain and psychiatric outcomes.
View Article and Find Full Text PDFCogn Affect Behav Neurosci
February 2021
The amygdala has been implicated in processing threat and learning fear. However, the amygdala also responds to motivationally relevant stimuli even in the absence of explicit emotional content. We investigated the relationship among amygdala activation, cognitive and emotional factors, and fMRI task data in participants from the Young Adult Human Connectome Project.
View Article and Find Full Text PDFBiol Psychiatry Cogn Neurosci Neuroimaging
June 2020
Background: Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder in adulthood, highlighting the importance of identifying neural correlates of childhood PLEs. Furthermore, impairment of cognitive functions, such as working memory and emotion regulation, has also been linked to psychosis risk as well as to disruptions in several brain regions. However, impairments in these domains have also been linked to other disorders, including depression.
View Article and Find Full Text PDFObjective: Reward system dysfunction is a well-known correlate and predictor of depression in adults and adolescents, with depressed individuals showing blunted (hyporeactive) striatal response to monetary rewards. Furthermore, studies of remitted depression suggest network-wide hyporeactivity of striatal (caudate, putamen, nucleus accumbens) and cortical (insula, anterior cingulate cortex [ACC]) regions even in the absence of current symptoms. Thus, it remains unclear which patterns of hyporeactivity represent a trait-like indicator of depression and which represent a current depressed state.
View Article and Find Full Text PDFChromosome instability (CIN) has been associated with therapeutic resistance in many cancers. However, whether tumours become genomically unstable as an evolutionary mechanism to overcome the bottleneck exerted by therapy is not clear. Using a CIN model of Kras-driven breast cancer, we demonstrate that aneuploid tumours acquire genetic modifications that facilitate the development of resistance to targeted therapy faster than euploid tumours.
View Article and Find Full Text PDFThe prefrontal cortex (PFC) comprises distinct regions and networks that vary in their trajectories across development. Further understanding these diverging trajectories may elucidate the neural mechanisms by which distinct PFC regions contribute to cognitive maturity. In particular, it remains unclear whether PFC regions of distinct network affiliations differ in topology and their relationship to cognition.
View Article and Find Full Text PDFNegative symptoms are a core clinical feature of schizophrenia that are only marginally responsive to current treatments. Recent work suggests that deficits in reinforcement learning and anticipatory responses to reward may be two mechanisms that help explain impairments in motivation in those with schizophrenia. The present study utilized a reinforcement-learning paradigm, which allowed us to examine both reward anticipation and reinforcement learning.
View Article and Find Full Text PDFBiol Psychiatry Cogn Neurosci Neuroimaging
October 2019
Background: Disorders with psychotic features, including schizophrenia and some bipolar disorders, are associated with impairments in regulation of goal-directed behavior, termed cognitive control. Cognitive control-related neural alterations have been studied in psychosis. However, studies are typically unimodal, and relationships across modalities of brain function and structure remain unclear.
View Article and Find Full Text PDFObjective: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial interindividual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC).
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