Beyond stereotypes of adolescent risk taking: Placing the adolescent brain in developmental context.

Recent neuroscience models of adolescent brain development attribute the morbidity and mortality of this period to structural and functional imbalances between more fully developed limbic regions that subserve reward and emotion as opposed to those that enable cognitive control. We challenge this interpretation of adolescent development by distinguishing risk-taking that peaks during adolescence (sensation seeking and impulsive action) from risk taking that declines monotonically from childhood to adulthood (impulsive choice and other decisions under known risk). Sensation seeking is primarily motivated by exploration of the environment under ambiguous risk contexts, while impulsive action, which is likely to be maladaptive, is more characteristic of a subset of youth with weak control over limbic motivation.

Globally weaker and topologically different: resting-state connectivity in youth with autism.

Background: There is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD). Studies using absolute strength have found reduced connectivity, while those using relative strength--a measure of system topology--reveal mostly enhanced connectivity. We hypothesized that mixed findings may be driven by the metric of functional connectivity.

Impact of early life adversity and tryptophan depletion on functional connectivity in menopausal women: A double-blind, placebo-controlled crossover study.

During the menopause transition, women are at increased risk of subjective symptoms of executive dysfunction. Evidence from animal and human participant studies suggests adverse childhood experiences (ACE) may be a risk factor for executive complaints during this hormonal transition. Preclinical literature indicates early life adversity effects on serotonin function may play a role in this increased susceptibility.

Modular Segregation of Structural Brain Networks Supports the Development of Executive Function in Youth.

The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence. However, it remains unknown whether the underlying white matter architecture is similarly refined during development, potentially allowing for improvements in executive function. In a sample of 882 participants (ages 8-22) who underwent diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that structural network modules become more segregated with age, with weaker connections between modules and stronger connections within modules.

Functional hypergraph uncovers novel covariant structures over neurodevelopment.

Brain development during adolescence is marked by substantial changes in brain structure and function, leading to a stable network topology in adulthood. However, most prior work has examined the data through the lens of brain areas connected to one another in large-scale functional networks. Here, we apply a recently developed hypergraph approach that treats network connections (edges) rather than brain regions as the unit of interest, allowing us to describe functional network topology from a fundamentally different perspective.

Large-scale sparse functional networks from resting state fMRI.

Delineation of large-scale functional networks (FNs) from resting state functional MRI data has become a standard tool to explore the functional brain organization in neuroscience. However, existing methods sacrifice subject specific variation in order to maintain the across-subject correspondence necessary for group-level analyses. In order to obtain subject specific FNs that are comparable across subjects, existing brain decomposition techniques typically adopt heuristic strategies or assume a specific statistical distribution for the FNs across subjects, and therefore might yield biased results.

Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood.

Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years.

Positive affect, surprise, and fatigue are correlates of network flexibility.

Advances in neuroimaging have made it possible to reconstruct functional networks from the activity patterns of brain regions distributed across the cerebral cortex. Recent work has shown that flexible reconfiguration of human brain networks over short timescales supports cognitive flexibility and learning. However, modulating network flexibility to enhance learning requires an understanding of an as-yet unknown relationship between flexibility and brain state.

Impact of Tryptophan Depletion on Executive System Function during Menopause is Moderated by Childhood Adversity.

Many healthy women with no history of cognitive dysfunction experience subjective executive difficulties during menopause. Preclinical literature suggests latent effects of early life adversity on serotonin function may play a role in this phenomenon. However, evidence in human participants regarding the mechanisms by which loss of estradiol contributes to this vulnerability is lacking.

Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity.

Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths.

Steeper discounting of delayed rewards in schizophrenia but not first-degree relatives.

Excessive discounting of future rewards has been related to a variety of risky behaviors and adverse clinical conditions. Prior work examining delay discounting in schizophrenia suggests an elevated discount rate. However, it remains uncertain whether this reflects the disease process itself or an underlying genetic vulnerability, whether it is selective for delay discounting or reflects pervasive changes in decision-making, and whether it is driven by specific clinical dimensions such as cognitive impairment.

Patterns of coordinated cortical remodeling during adolescence and their associations with functional specialization and evolutionary expansion.

During adolescence, the human cortex undergoes substantial remodeling to support a rapid expansion of behavioral repertoire. Accurately quantifying these changes is a prerequisite for understanding normal brain development, as well as the neuropsychiatric disorders that emerge in this vulnerable period. Past accounts have demonstrated substantial regional heterogeneity in patterns of brain development, but frequently have been limited by small samples and analytics that do not evaluate complex multivariate imaging patterns.

Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD.

Background: Both major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders.

Methods: 53 unmedicated right-handed participants were included in a longitudinal study.

The modular organization of human anatomical brain networks: Accounting for the cost of wiring.

Brain networks are expected to be modular. However, existing techniques for estimating a network's modules make it difficult to assess the influence of organizational principles such as wiring cost reduction on the detected modules. Here we present a modification of an existing module detection algorithm that allowed us to focus on connections that are unexpected under a cost-reduction wiring rule and to identify modules from among these connections.

Evolution of brain network dynamics in neurodevelopment.

Cognitive function evolves significantly over development, enabling flexible control of human behavior. Yet, how these functions are instantiated in spatially distributed and dynamically interacting networks, or that change in structure from childhood to adolescence is far from understood. Here we applied a novel machine-learning method to track continuously overlapping and time-varying subgraphs in the brain at rest within a sample of 200 healthy youth (ages 8-11 and 19-22) drawn from the Philadelphia Neurodevelopmental Cohort.

Common Dimensional Reward Deficits Across Mood and Psychotic Disorders: A Connectome-Wide Association Study.

Objective: Anhedonia is central to multiple psychiatric disorders and causes substantial disability. A dimensional conceptualization posits that anhedonia severity is related to a transdiagnostic continuum of reward deficits in specific neural networks. Previous functional connectivity studies related to anhedonia have focused on case-control comparisons in specific disorders, using region-specific seed-based analyses.

Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two-year follow-up.

Prospective evaluation of youths with early psychotic-like experiences can enrich our knowledge of clinical, biobehavioral and environmental risk and protective factors associated with the development of psychotic disorders. We aimed to investigate the predictors of persistence or worsening of psychosis spectrum features among US youth through the first large systematic study to evaluate subclinical symptoms in the community. Based on Time 1 screen of 9,498 youth (age 8-21) from the Philadelphia Neurodevelopmental Cohort, a subsample of participants was enrolled based on the presence (N=249) or absence (N=254) of baseline psychosis spectrum symptoms, prior participation in neuroimaging, and current neuroimaging eligibility.

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety.

Background: Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences.

Disrupted anatomic networks in the 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) is an uncommon genetic disorder with an increased risk of psychosis. Although the neural substrates of psychosis and schizophrenia are not well understood, aberrations in cortical networks represent intriguing potential mechanisms.

Temporal Lobe Volume Decrements in Psychosis Spectrum Youths.

Structural brain abnormalities have been amply demonstrated in schizophrenia. These include volume decrements in the perirhinal/entorhinal regions of the ventromedial temporal lobe, which comprise the primary olfactory cortex. Olfactory impairments, which are a hallmark of schizophrenia, precede the onset of illness, distinguish adolescents experiencing prodromal symptoms from healthy youths, and may predict the transition from the prodrome to frank psychosis.

Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression.

Neuroimaging studies of mood disorders demonstrate abnormalities in brain regions implicated in reward processing. However, there is a paucity of research investigating how social rewards affect reward circuit activity in these disorders. Here, we evaluated the relationship of both diagnostic category and dimensional depression severity to reward system function in bipolar and unipolar depression.

Neural Markers of the Development of Executive Function: Relevance for Education.

Executive functions are involved in the development of academic skills and are critical for functioning in school settings. The relevance of executive functions to education begins early and continues throughout development, with clear impact on achievement. Diverse efforts increasingly suggest ways in which facilitating development of executive function may be used to improve academic performance.

Structural Brain Abnormalities in Youth With Psychosis Spectrum Symptoms.

Importance: Structural brain abnormalities are prominent in psychotic disorders, including schizophrenia. However, it is unclear when aberrations emerge in the disease process and if such deficits are present in association with less severe psychosis spectrum (PS) symptoms in youth.

Objective: To investigate the presence of structural brain abnormalities in youth with PS symptoms.

Subject-level measurement of local cortical coupling.

The human cortex is highly folded to allow for a massive expansion of surface area. Notably, the thickness of the cortex strongly depends on cortical topology, with gyral cortex sometimes twice as thick as sulcal cortex. We recently demonstrated that global differences in thickness between gyral and sulcal cortex continue to evolve throughout adolescence.