A canonical trajectory of executive function maturation from adolescence to adulthood.

Theories of human neurobehavioral development suggest executive functions mature from childhood through adolescence, underlying adolescent risk-taking and the emergence of psychopathology. Investigations with relatively small datasets or narrow subsets of measures have identified general executive function development, but the specific maturational timing and independence of potential executive function subcomponents remain unknown. Integrating four independent datasets (N = 10,766; 8-35 years old) with twenty-three measures from seventeen tasks, we provide a precise charting, multi-assessment investigation, and replication of executive function development from adolescence to adulthood.

Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition.

Striatal dopamine supports reward expectation and learning: A simultaneous PET/fMRI study.

Converging evidence from both human neuroimaging and animal studies has supported a model of mesolimbic processing underlying reward learning behaviors, based on the computation of reward prediction errors. However, competing evidence supports human dopamine signaling in the basal ganglia as also contributing to the generation of higher order learning heuristics. Here, we present data from a large (N = 81, 18-30yo), multi-modal neuroimaging study using simultaneously acquired task fMRI, affording temporal resolution of reward system function, and PET imaging with [C]Raclopride (RAC), assessing striatal dopamine (DA) D2/3 receptor binding, during performance of a probabilistic reward learning task.

Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study.

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited.

Puberty contributes to adolescent development of fronto-striatal functional connectivity supporting inhibitory control.

Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive improvements.

Pubertal development underlies optimization of inhibitory control through specialization of ventrolateral prefrontal cortex.

Inhibitory control improves into young adulthood after specialization of relevant brain systems during adolescence. However, the biological mechanisms supporting this unique transition are not well understood. Given that adolescence is defined by puberty, we examined relative contributions of chronological age and pubertal maturation to inhibitory control development.

A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia.

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response.

Subcortical brain iron deposition in individuals with schizophrenia.

Subcortical structures play a critical role the pathophysiology and treatment of schizophrenia (SZ), yet underlying neurophysiological processes, in vivo, remain largely unexplored. Brain tissue iron, which can be measured with magnetic resonance-based methods, is a crucial component of a variety of neuronal functions including neurotransmitter synthesis. Here we used a proxy measure of tissue iron to examine basal ganglia and thalamic structures in an adult cohort of individuals with chronic SZ.

Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistant schizophrenia.

Rationale: Though numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ's efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ's unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning.

Relationship between plasma clozapine/N-desmethylclozapine and changes in basal forebrain-dorsolateral prefrontal cortex coupling in treatment-resistant schizophrenia.

Clozapine (CLZ) demonstrates a unique clinical efficacy relative to other antipsychotic drugs. Previous work has linked the plasma ratio of CLZ and its major metabolite, N-desmethylclozapine (NDMC), to an inverse relationship with cognition via putative action on the cholinergic system. However, neuroimaging correlates of CLZ/NDMC remain unknown.

Reproducible brain-wide association studies require thousands of individuals.

Magnetic 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)).

Hippocampal-Prefrontal Connectivity Prior to the COVID-19 Pandemic Predicts Stress Reactivity.

Background: By adolescence, foundational cognitive and affective neurobehavioral processes specialize based on environmental demands, such as stress, to determine the basis of adult trajectories. The ongoing COVID-19 pandemic has increased stress for everyone, particularly adolescents who face unique stressors such as restrictions in socialization and education. However, variability in brain processes supporting stress reactivity is not well understood.

Increased Functional Coupling between VTA and Hippocampus during Rest in First-Episode Psychosis.

Animal models suggest that interactions between the hippocampus and ventral tegmental area (VTA) underlie the onset and etiology of psychosis. While a large body of research has separately characterized alterations in hippocampal and VTA function in psychosis, alterations across the VTA and hippocampus have not been characterized in first-episode psychosis (FEP). As the phase of psychosis most proximal to conversion, studies specifically focused on FEP are valuable to psychosis research.

Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition.

Background: Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with 'background connectivity' following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders.

Influences of affective context on amygdala functional connectivity during cognitive control from adolescence through adulthood.

Emotion processing is believed to dominate over other brain functions during adolescence, including inhibitory control. However, few studies have examined the neural underpinnings of affective states during cognitive control. Here, we characterized the brain in an affective state by cross-sectionally assessing age-related changes in amygdala background connectivity during an affective inhibitory control task.

Functional connectome fingerprinting accuracy in youths and adults is similar when examined on the same day and 1.5-years apart.

Pioneering studies have shown that individual correlation measures from resting-state functional magnetic resonance imaging studies can identify another scan from that same individual. This method is known as "connectotyping" or functional connectome "fingerprinting." We analyzed a unique dataset of 12-30 years old (N = 140) individuals who had two distinct resting state scans on the same day and again 12-18 months later to assess the sensitivity and specificity of fingerprinting accuracy across different time scales (same day, ~1.

Adolescent development of inhibitory control and substance use vulnerability: A longitudinal neuroimaging study.

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at-risk youth follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol study, participants (N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points.

Independent support for corticopallidal contributions to schizophrenia-related functional impairment.

Background: Abnormalities between the prefrontal cortex and basal ganglia have been described by numerous studies of schizophrenia (SZ). We recently reported that individuals with first episode SZ who develop greater vocational and social impairments show lower baseline functional connectivity between the globus pallidus (GP) and regions of the intrinsic salience network. Here we extend these findings to probe the integrity of this system in individuals with chronic illness.

Meta-analysis and review of functional neuroimaging differences underlying adolescent vulnerability to substance use.

Adolescence is increasingly viewed as a sensitive period in the development of substance use disorders (SUDs). Neurodevelopmental 'dual-risk' theories suggest adolescent vulnerability to problematic substance use is driven by an overactive reward drive mediated by the striatum, and poor cognitive control mediated by the prefrontal cortex. To this end, there has been a growing number of neuroimaging studies examining cognitive and affective neural systems during adolescence for markers of vulnerability to problematic substance use.

Identifying reproducible individual differences in childhood functional brain networks: An ABCD study.

The 21-site Adolescent Brain Cognitive Development (ABCD) study provides an unparalleled opportunity to characterize functional brain development via resting-state functional connectivity (RSFC) and to quantify relationships between RSFC and behavior. This multi-site data set includes potentially confounding sources of variance, such as differences between data collection sites and/or scanner manufacturers, in addition to those inherent to RSFC (e.g.

Resting-State Functional Network Organization Is Stable Across Adolescent Development for Typical and Psychosis Spectrum Youth.

Background: Resting-state functional neuroimaging captures large-scale network organization; whether this organization is intact or disrupted during adolescent development across the psychosis spectrum is unresolved. We investigated the integrity of network organization in psychosis spectrum youth and those with first episode psychosis (FEP) from late childhood through adulthood.

Methods: We analyzed data from Philadelphia Neurodevelopmental Cohort (PNC; typically developing = 450, psychosis spectrum = 273, 8-22 years), a longitudinal cohort of typically developing youth (LUNA; N = 208, 1-3 visits, 10-25 years), and a sample of FEP (N = 39) and matched controls (N = 34).

Intrinsic Connectivity of the Globus Pallidus: An Uncharted Marker of Functional Prognosis in People With First-Episode Schizophrenia.

There is growing evidence suggesting that abnormalities in cortical-basal ganglia circuitry may play a significant role in determining outcomes in schizophrenia. The globus pallidus (GP), a critical structure within this circuitry, unique in its role as a mediator of competing inputs through the striatum, has not been well characterized in schizophrenia. The following study examined functional interactions of the GP in individuals with first-episode schizophrenia (FES).

Association Between Duration of Untreated Psychosis and Frontostriatal Connectivity During Maintenance of Visuospatial Working Memory.

Background: A longer duration of untreated psychosis (DUP) has been linked with poor clinical outcomes and variation in resting-state striatal connectivity with central executive regions. However, the link between DUP and task-based activation of executive neurocognition has not previously been examined. This functional magnetic resonance imaging study examined the association between DUP and both activation and frontostriatal functional connectivity during a visual working memory (WM) paradigm in patients with first-episode psychosis.