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Objective: Schizotypal personality traits are associated with schizophrenia spectrum disorders, and individuals with schizophrenia spectrum disorders demonstrate increased dopamine transmission in the striatum. The authors sought to determine whether individual differences in normal variation in schizotypal traits are correlated with dopamine transmission in the striatum and in extrastriatal brain regions.Method: Sixty-three healthy volunteers with no history of psychiatric illness completed the Schizotypal Personality Questionnaire and underwent positron emission tomography imaging with [(18)F]fallypride at baseline and after administration of oral d-amphetamine (0.43 mg/kg). Dopamine release, quantified by subtracting each participant's d-amphetamine scan from his or her baseline scan, was correlated with Schizotypal Personality Questionnaire total and factor scores using region-of-interest and voxel-wise analyses.Results: Dopamine release in the striatum was positively correlated with overall schizotypal traits. The association was especially robust in the associative subdivision of the striatum. Voxel-wise analyses identified additional correlations between dopamine release and schizotypal traits in the left middle frontal gyrus and left supramarginal gyrus. Exploratory analyses of Schizotypal Personality Questionnaire factor scores revealed correlations between dopamine release and disorganized schizotypal traits in the striatum, thalamus, medial prefrontal cortex, temporal lobe, insula, and inferior frontal cortex.Conclusions: The association between dopamine signaling and psychosis phenotypes extends to individual differences in normal variation in schizotypal traits and involves dopamine transmission in both striatal and extrastriatal brain regions. Amphetamine-induced dopamine release may be a useful endophenotype for investigating the genetic basis of schizophrenia spectrum disorders. [ABSTRACT FROM AUTHOR]

Background: From a neuroeconomics perspective, decisions about what to eat are ultimately determined by basic features of how the brain codes and contrasts the values of different rewards and the potential positive or negative consequences of eating the food. Several brain regions play a role in this valuation and comparison process. Among these regions, the orbitofrontal cortex (OFC), which occupies the ventral surface of the frontal lobe, plays a critical integrative role in these processes. An examination of the influences on valuation both within the OFC and in related brain regions reveals several features that are likely to impact food selection. These include coding of rewards relative to other available rewards, general and specific satiety, and temporal discounting. The OFC also processes information about negative valuations (i.e., cost, negative health consequences), which are influenced by factors such as temporal discounting, probability and ambiguity.Conclusion: An understanding of these influences on positive and negative valuation is critical in designing diets and public health programs aimed at promoting healthy eating. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Schizophrenia is associated with a decreased pursuit of risky rewards during uncertain-risk decision-making. However, putative mechanisms subserving this disadvantageous risky reward pursuit, such as contributions of cognition and relevant traits, remain poorly understood., Study Design: Participants (30 schizophrenia/schizoaffective disorder [SZ]; 30 comparison participants [CP]) completed the Balloon Analogue Risk Task (BART). Computational modeling captured subprocesses of uncertain-risk decision-making: Risk Propensity, Prior Belief of Success, Learning Rate, and Behavioral Consistency. IQ, self-reported risk-specific processes (ie, Perceived Risks and Expected Benefit of Risks), and non-risk-specific traits (ie, defeatist beliefs; hedonic tone) were examined for relationships with Risk Propensity to determine what contributed to differences in risky reward pursuit., Study Results: On the BART, the SZ group exhibited lower Risk Propensity, higher Prior Beliefs of Success, and comparable Learning Rates. Furthermore, Risk Propensity was positively associated with IQ across groups. Linear models predicting Risk Propensity revealed 2 interactions: 1 between group and Perceived Risk, and 1 between IQ and Perceived Risk. Specifically, in both the SZ group and individuals with below median IQ, lower Perceived Risks was related to lower Risk Propensity. Thus, lower perception of financial risks was associated with a less advantageous pursuit of uncertain-risk rewards., Conclusions: Findings suggest consistently decreased risk-taking on the BART in SZ may reflect risk imperception, the failure to accurately perceive and leverage relevant information to guide the advantageous pursuit of risky rewards. Additionally, our results highlight the importance of cognition in uncertain-risk decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms. The superspectrum includes psychoticism and detachment spectra as well as narrow subdimensions within them. Auxiliary domains of cognitive deficit and functional impairment complete the psychopathology profile. The current paper reviews evidence on this model from neurobiology, treatment response, clinical utility, and measure development. Neurobiology research suggests that psychopathology included in the superspectrum shows similar patterns of neural alterations. Treatment response often mirrors the hierarchy of the superspectrum with some treatments being efficacious for psychoticism, others for detachment, and others for a specific subdimension. Compared to traditional diagnostic systems, the quantitative nosology shows an approximately 2-fold increase in reliability, explanatory power, and prognostic accuracy. Clinicians consistently report that the quantitative nosology has more utility than traditional diagnoses, but studies of patients with frank psychosis are currently lacking. Validated measures are available to implement the superspectrum model in practice. The dimensional conceptualization of psychosis-related psychopathology has implications for research, clinical practice, and public health programs. For example, it encourages use of the cohort study design (rather than case-control), transdiagnostic treatment strategies, and selective prevention based on subclinical symptoms. These approaches are already used in the field, and the superspectrum provides further impetus and guidance for their implementation. Existing knowledge on this model is substantial, but significant gaps remain. We identify outstanding questions and propose testable hypotheses to guide further research. Overall, we predict that the more informative, reliable, and valid characterization of psychopathology offered by the superspectrum model will facilitate progress in research and clinical care., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Developmental literature suggests that susceptibility to social conformity pressure peaks in adolescence and disappears with maturity into early adulthood. Predictions about these behaviors are less clear for middle-aged and older adults. On the one hand, while age-related increases in prioritization of socioemotional goals might predict greater susceptibility to social conformity pressures, aging is also associated with enhanced emotion regulation that could support resistance to conformity pressures. In this exploratory research study, we used mobile experience sampling surveys to naturalistically track how 157 healthy adults between the ages of 18 and 80 practice self-control over spontaneous desires in daily life. Many of these desires were experienced in the presence of others enacting that desire. Results showed that middle-aged and older adults were better at controlling their desires than younger adults when desires were experienced in the presence of others enacting that desire. Consistent with the literature on improved emotion regulation with age, these results provide evidence that the ability to resist social conformity pressure is enhanced across the adult life span. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D 2/3 autoreceptors in mesocorticolimbic circuits. While altered D 2/3 binding is noted in ICB + PD patients, there is limited prior assessment of the trait impulsivity-D 2/3 relationship in PD, and no prior direct comparison with patterns in HCs. We examined 54 PD (36 M; 18 F) and 31 sex- and age-matched HC (21 M; 10 F) subjects using [ 18 F]fallypride, a high-affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). Subcortical and cortical assessment exclusively used ROI or exploratory-voxelwise methods, respectively. All completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. Subcortical ROI analyses indicated a negative relationship between trait impulsivity and D 2/3 BP ND in the ventral striatum and amygdala of HCs but not in PD. By contrast, voxelwise methods demonstrated a positive trait impulsivity-D 2/3 BP ND correlation in ventral frontal olfactocentric-paralimbic cortex of subjects with PD but not HCs. Subscale analysis also highlighted different aspects of impulsivity, with significant interactions between group and motor impulsivity in the ventral striatum, and attentional impulsivity in the amygdala and frontal paralimbic cortex. These results suggest that dopamine functioning in distinct regions of the mesocorticolimbic circuit influence aspects of impulsivity, with the relative importance of regional dopamine functions shifting in the neuropharmacological context of PD. SIGNIFICANCE STATEMENT The biological determinants of impulsivity have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease. This is the first study to evaluate a large cohort of Parkinson's disease patients and age-matched healthy controls with a measure of trait impulsivity and concurrent [ 18 F]fallypride PET, a method that allows quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in the trait impulsivity-dopamine relationship, including (1) loss of subcortical relationships present in the healthy brain and (2) emergence of a new relationship in a limbic cortical area. This illustrates the loss of mechanisms of behavioral regulation present in the healthy brain while suggesting a potential compensatory response and target for future investigation., (Copyright © 2023 the authors.)

As a major regulator of dopamine (DA), DA autoreceptors (DA ARs ) exert substantial influence over DA-mediated behaviors. This paper reviews the physiological and behavioral impact of DA ARs . Individual differences in DA AR functioning influences temperamental traits such as novelty responsivity and impulsivity, both of which are associated with vulnerability to addictive behavior in animal models and a broad array of externalizing behaviors in humans. DA ARs additionally impact the response to psychostimulants and other drugs of abuse. Human PET studies of D2-like receptors in the midbrain provide evidence for parallels to the animal literature. These data lead to the proposal that weak DA AR regulation is a risk factor for addiction and externalizing problems. The review highlights the potential to build translational models of the functional role of DA ARs in behavior. It also draws attention to key limitations in the current literature that would need to be addressed to further advance a weak DA AR regulation model of addiction and externalizing risk., Competing Interests: Declarations of interest None, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Antisocial behaviors are common and problematic among patients with behavioral variant frontotemporal dementia (bvFTD). In the present study, the investigators aimed to validate an informant-based questionnaire developed to measure the extent and severity of antisocial behaviors among patients with dementia., Methods: The Social Behavior Questionnaire (SBQ) was developed to measure 26 antisocial behaviors on a scale from absent (0) to very severe (5). It was administered to 23 patients with bvFTD, 19 patients with Alzheimer's disease, and 14 patients with other frontotemporal lobar degeneration syndromes. Group-level differences in the presence and severity of antisocial behaviors were measured. Psychometric properties of the SBQ were assessed by using Cronbach's alpha, exploratory factor analysis, and comparisons with a psychopathy questionnaire. Cluster analysis was used to determine whether the SBQ identifies different subgroups of patients., Results: Antisocial behaviors identified by using the SBQ were common and severe among patients with bvFTD, with at least one such behavior endorsed for 21 of 23 (91%) patients. Antisocial behaviors were more severe among patients with bvFTD, including the subsets of patients with milder cognitive impairment and milder disease severity, than among patients in the other groups. The SBQ was internally consistent (Cronbach's α=0.81). Exploratory factor analysis supported separate factors for aggressive and nonaggressive behaviors. Among the patients with bvFTD, the factor scores for aggressive behavior on the SBQ were correlated with those for antisocial behavior measured on the psychopathy scale, but the nonaggressive scores were not correlated with psychopathy scale measures. The k-means clustering analysis identified a subset of patients with severe antisocial behaviors., Conclusions: The SBQ is a useful tool to identify, characterize, and measure the severity of antisocial behaviors among patients with dementia., Competing Interests: Dr. Claassen has received research support from the Griffin Foundation, the Huntington’s Disease Society of America, the National Center for Complementary and Integrative Health, the National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, and NIH; he has received pharmaceutical grant support from AbbVie, Acadia, Biogen, Bristol Myers Squibb, Cerecour, Eli Lilly, Jazz Pharmaceuticals, Lundbeck, Teva Neuroscience, Wave Life Sciences, and Vaccinex; and he has received personal fees for consulting and advisory board participation from Cerevel, Lundbeck, Neurocrine, and Teva Neuroscience. The other authors report no financial relationships with commercial interests.

Objective: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder [AUD]), identifying novel research and treatment targets and developing new study designs is daunting., Method: In this article, we review and integrate two recently developed frameworks, the National Institute on Drug Abuse's Phenotyping Assessment Battery (NIDA PhAB) and the Hierarchical Taxonomy of Psychopathology (HiTOP), that hope to accelerate progress in understanding the causes and consequences of psychopathology by means of deep phenotyping, or finer-grained analysis of phenotypes., Results and Conclusions: NIDA PhAB focuses on addiction-related processes across multiple units of analysis, whereas HiTOP focuses on clinical phenotypes and covers a broader range of psychopathology. We highlight that NIDA PhAB and HiTOP together provide deep and broad characterizations of people diagnosed with SUDs and complement each other in their efforts to address widely known limitations of traditional classification systems and their diagnostic categories. Next, we show how NIDA PhAB and HiTOP can be integrated to facilitate optimal rich phenotyping of addiction-related phenomena. Finally, we argue that such deep phenotyping promises to advance our understanding of the neurobiology of SUD and addiction, which will guide the development of personalized medicine and interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Language comprehension requires the rapid retrieval and integration of contextually appropriate concepts ("semantic cognition"). Current neurobiological models of semantic cognition are limited by the spatial and temporal restrictions of single-modality neuroimaging and lesion approaches. This is a major impediment given the rapid sequence of processing steps that have to be coordinated to accurately comprehend language. Through the use of fused functional magnetic resonance imaging and electroencephalography analysis in humans ( n = 26 adults; 15 females), we elucidate a temporally and spatially specific neurobiological model for real-time semantic cognition. We find that semantic cognition in the context of language comprehension is supported by trade-offs between widespread neural networks over the course of milliseconds. Incorporation of spatial and temporal characteristics, as well as behavioral measures, provide convergent evidence for the following progression: a hippocampal/anterior temporal phonological semantic retrieval network (peaking at ∼300 ms after the sentence final word); a frontotemporal thematic semantic network (∼400 ms); a hippocampal memory update network (∼500 ms); an inferior frontal semantic syntactic reappraisal network (∼600 ms); and nodes of the default mode network associated with conceptual coherence (∼750 ms). Additionally, in typical adults, mediatory relationships among these networks are significantly predictive of language comprehension ability. These findings provide a conceptual and methodological framework for the examination of speech and language disorders, with additional implications for the characterization of cognitive processes and clinical populations in other cognitive domains. SIGNIFICANCE STATEMENT The present study identifies a real-time neurobiological model of the meaning processes required during language comprehension (i.e., "semantic cognition"). Using a novel application of fused magnetic resonance imaging and electroencephalography in humans, we found that semantic cognition during language comprehension is supported by a rapid progression of widespread neural networks related to meaning, meaning integration, memory, reappraisal, and conceptual cohesion. Relationships among these systems were predictive of individuals' language comprehension efficiency. Our findings are the first to use fused neuroimaging analysis to elucidate language processes. In so doing, this study provides a new conceptual and methodological framework in which to characterize language processes and guide the treatment of speech and language deficits/disorders., (Copyright © 2023 the authors.)

A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

[Correction Notice: An Erratum for this article was reported online in Emotion on May 16 2022 (see record 2022-64181-001). In the article "Emotional Distractor Images Disrupt Target Processing in a Graded Manner" by Jonathan M. Keefe and David H. Zald ( Emotion , advance online publication, August 27, 2020, https://doi.org/10.1037/emo0000893), there were errors in the reporting of nonresponse rate and accuracy data. Nonresponse rate was underreported for the data in the Lag 2 condition, resulting in incorrect analysis of variance values for this portion of the Results section as well as incorrect Lag 2 t-test values in Table 1 and incorrect Lag 2 values in Figure 2A. Additionally, error bars for the accuracy data in Figure 2B were mistakenly calculated with data including excluded trials, resulting in larger estimates of standard error of the mean. These corrections do not affect the interpretation of any inferential statistics and in fact increased the effect of lag and distractor valence upon both of these measures. Therefore, no conclusions of the study are altered. All versions of this article have been corrected.] The emotional attentional blink (EAB), also referred to as emotion-induced blindness, refers to a transient impairment in the ability to discriminate a single target when it is presented closely in time to an emotional distractor. Although the EAB has typically been characterized as representing a complete loss of target information due to attentional capture by the emotional distractors, it is unclear whether the impact of the emotional distractor is in fact discrete or graded. Here, we tested whether the emotional distractor of the EAB interfered with target processing in a continuous or all-or-none manner by measuring changes in both reaction time (RT) and target-vividness ratings in addition to target-discrimination accuracy. Rapid sequences of landscape images were presented centrally, and participants reported the orientation of a ± 90° rotated target as quickly and accurately as possible. Replicating the classic EAB phenomenon, we found a strong impairment in target discrimination when an emotional distractor shortly preceded the target, and we also found a moderate impairment when the target preceded an emotional distractor. This decrement in accuracy at short lags was accompanied by increases in RT to the target as well as lower ratings of subjective target vividness even when the target was detected, indicating that emotional distractors impacted target processing in a lag-dependent, graded manner. We argue that these results are consistent with an interactive race model of the competition between stimulus representations in the conflict between top-down and bottom-up attentional mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Although theoretical models suggest that an attentional bias for threat contributes to the development of post-traumatic stress disorder (PTSD) symptoms, this bias has not been consistently observed in the literature. In the present study, trauma exposed veterans (N = 114) performed an emotional attentional blink task in which task-irrelevant combat-related, disgust, positive, or neutral distractor images appeared 200 ms, 400 ms, 600 ms, or 800 ms (i.e., lag 2, 4, 6, and 8, respectively) before the target. Relative to neutral distractors, impaired target detection was observed following combat distractors and disgust distractors, but not positive distractors. However, veterans were less accurate following disgust distractors compared to combat distractors. As predicted, combat distractors and disgust distractors were also associated with a stronger linear increase in trial accuracy reflecting task improvement with increasing lag before the target. However, the linear trend in trial accuracy for combat distractors and disgust distractors did not significantly differ from each other. Contrary to predictions, trauma specific (i.e., PTSD symptoms and diagnosis) and nonspecific processes (i.e., attentional control) were unrelated to trial accuracy. These data suggest that while initial attentional capture by cues of war is observed among trauma exposed veterans independent of individual differences in trauma specific and nonspecific symptoms, this attentional capture is less robust compared to attentional capture by disgust-eliciting stimuli. The implications of these findings for the theorized role of attentional biases for threat in the development and maintenance of PTSD are discussed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D 2 receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded d-amphetamine (dAMPH) study. Participants completed [ 18 F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BP ND ) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D 2 -like BP ND in the amygdala and hippocampus (right cluster q FDR-corr = 0.026, left cluster q FDR-corr = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = -48.26, p = 0.005) and hippocampus (coefficient = -104.94, p = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected. SIGNIFICANCE STATEMENT While Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded d-amphetamine (dAMPH) study, with [ 18 F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D 2 -like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BP ND associated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population., (Copyright © 2021 the authors.)

Substantial evidence implicates the amygdala and related structures in the processing of negative emotions. Furthermore, neuroimaging evidence suggests that variations in amygdala volumes are related to trait-like individual differences in neuroticism/negative emotionality, although many questions remain about the nature of such associations. We conducted planned tests of the directional prediction that dispositional negative emotionality measured at 10-17 years using parent and youth ratings on the Child and Adolescent Dispositions Scale (CADS) would predict larger volumes of the amygdala in adulthood and conducted exploratory tests of associations with other regions implicated in emotion processing. Participants were 433 twins strategically selected for neuroimaging during wave 2 from wave 1 of the Tennessee Twins Study (TTS) by oversampling on internalizing and/or externalizing psychopathology risk. Controlling for age, sex, race-ethnicity, handedness, scanner, and total brain volume, youth-rated negative emotionality positively predicted bilateral amygdala volumes after correction for multiple testing. Each unit difference of one standard deviation (SD) in negative emotionality was associated with a .12 SD unit difference in larger volumes of both amygdalae. Parent-rated negative emotionality predicted greater thickness of the left caudal/dorsal anterior cingulate cortex (β = 0.28). Associations of brain structure with negative emotionality were not moderated by sex. These results are striking because dispositions assessed at 10-17 years of age were predictive of grey matter volumes measured 12-13 years later in adulthood. Future longitudinal studies should examine the timing of amygdala/cingulate associations with dispositional negative emotionality to determine when these associations emerge during development., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate "regions" rather than as white matter "bundles" or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different automated state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic., (© 2021 World Psychiatric Association.)

Older adults report experiencing improved emotional health, such as more intense positive affect and less intense negative affect. However, there are mixed findings on whether older adults are better at regulating emotion-a hallmark feature of emotional health-and most research is based on laboratory studies that may not capture how people regulate their emotions in everyday life. We used experience sampling to examine how multiple measures of emotional health, including mean affect, dynamic fluctuations between affective states and the ability to resist desires-a common form of emotion regulation-differ in daily life across adulthood. Participants ( N = 122, ages 20-80) reported how they were feeling and responding to desire temptations for 10 days. Older adults experienced more intense positive affect, less intense negative affect, and were more emotionally stable, even after controlling for individual differences in global life satisfaction. Older adults were more successful at regulating desires, even though they experienced more intense desires than younger adults. In addition, adults in general experiencing more intense affect were less successful at resisting desires. These results demonstrate how emotional experience is related to more successful desire regulation in everyday life and provide unique evidence that emotional health and regulation improve with age. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

There is an ongoing revolution in psychology and psychiatry that will likely change how we conceptualize, study and treat psychological problems.- Many theorists now support viewing psychopathology as consisting of continuous dimensions rather than discrete diagnostic categories. Indeed, recent papers have proposed comprehensive taxonomies of psychopathology dimensions to replace the DSM and ICD taxonomies of categories. The proposed dimensional taxonomies, which portray psychopathology as hierarchically organized correlated dimensions, are now well supported at phenotypic levels. Multiple studies show that both a general factor of psychopathology at the top of the hierarchy and specific factors at lower levels predict different functional outcomes. Our analyses of data on a large representative sample of child and adolescent twins suggested the causal hypothesis that phenotypic correlations among dimensions of psychopathology are the result of many familial influences being pleiotropic. That is, most genetic variants and shared environmental factors are hypothesized to non-specifically influence risk for multiple rather than individual dimensions of psychopathology. In contrast, person-specific experiences tend to be related to individual dimensions. This hierarchical causal hypothesis has been supported by both large-scale family and molecular genetic studies. Current research focuses on three issues. First, the field has not settled on a preferred statistical model for studying the hierarchy of causes and phenotypes. Second, in spite of encouraging progress, the neurobiological correlates of the hierarchy of dimensions of psychopathology are only partially described. Third, although there are potentially important clinical implications of the hierarchical model, insufficient research has been conducted to date to rec-ommend evidence-based clinical practices., (© 2021 World Psychiatric Association.)

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

Sluggish cognitive tempo (SCT) is characterized by behavioral symptoms reflecting slowness and lethargy (e.g., sluggishness, appearing sleepy) and inconsistent alertness/mental confusion (e.g., daydreaming, fogginess). SCT is substantially correlated with the inattentive symptoms of attention-deficit/hyperactivity disorder (ADHD) and may be part of that domain, but in cross-sectional data, SCT is also strongly associated with both inattention and depression. To date, no study has examined the prospective associations of SCT symptoms in childhood/adolescence with symptoms of ADHD and internalizing problems in adulthood. Using a sample of 449 twin children and adolescent pairs, prospective multiple regression analyses examined whether self- and parent-reported SCT, depression, and parent-reported symptoms of ADHD predicted symptoms in adulthood 12 years later. SCT and depression at time one were strongly correlated (self-reported SCT and depression r = 0.84; parent-reported SCT and depression r = 0.78). When adult outcomes were separately regressed on each youth symptom dimension, self-reported SCT (β = 0.26, p < 0.0001) and depression (β = 0.13, p < 0.0001) each predicted adult symptoms of depression and self-reported SCT predicted inattention (β = 0.12, p = 0.0026). Parent-reported depression, but not parent-reported SCT, predicted self-reported adult depression symptoms (β = 0.17, p = 0.0003). In contrast, when each adult outcome was regressed simultaneously on youth self-reported SCT and depression, neither predicted adulthood inattention or depression. These findings indicate that SCT in childhood and adolescence is strongly associated concurrently and predictively with both inattention and depression. Theoretical and clinical applications of the construct of SCT must take its robust association with both inattention and depression into account.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a scientific effort to address shortcomings of traditional mental disorder diagnoses, which suffer from arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. This paper synthesizes evidence on the validity and utility of the thought disorder and detachment spectra of HiTOP. These spectra are composed of symptoms and maladaptive traits currently subsumed within schizophrenia, other psychotic disorders, and schizotypal, paranoid and schizoid personality disorders. Thought disorder ranges from normal reality testing, to maladaptive trait psychoticism, to hallucinations and delusions. Detachment ranges from introversion, to maladaptive detachment, to blunted affect and avolition. Extensive evidence supports the validity of thought disorder and detachment spectra, as each spectrum reflects common genetics, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, biomarkers, and treatment response. Some of these characteristics are specific to one spectrum and others are shared, suggesting the existence of an overarching psychosis superspectrum. Further research is needed to extend this model, such as clarifying whether mania and dissociation belong to thought disorder, and explicating processes that drive development of the spectra and their subdimensions. Compared to traditional diagnoses, the thought disorder and detachment spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and higher acceptability to clinicians. Validated measures are available to implement the system in practice. The more informative, reliable and valid characterization of psychosis-related psychopathology offered by HiTOP can make diagnosis more useful for research and clinical care., (© 2020 World Psychiatric Association.)

Predictive associations were estimated between socioemotional dispositions measured at 10-17 years using the Child and Adolescent Dispositions Scale (CADS) and future individual differences in white matter microstructure measured at 22-31 years of age. Participants were 410 twins (48.3% monozygotic) selected for later neuroimaging by oversampling on risk for psychopathology from a representative sample of child and adolescent twins. Controlling for demographic covariates and total intracranial volume (TICV), each CADS disposition (negative emotionality, prosociality, and daring) rated by one of the informants (parent or youth) significantly predicted global fractional anisotropy (FA) averaged across the major white matter tracts in brain in adulthood, but did so through significant interactions with sex after false discovery rate (FDR) correction. In females, each 1 SD difference in greater parent-rated prosociality was associated with 0.43 SD greater FA ( p < 0.0008). In males, each 1 SD difference in greater parent-rated daring was associated with 0.24 SD lower FA ( p < 0.0008), and each 1 SD difference in greater youth-rated negative emotionality was associated with 0.18 SD greater average FA ( p < 0.0040). These findings suggest that CADS dispositions are associated with FA, but associations differ by sex. Exploratory analyses suggest that FA may mediate the associations between dispositions and psychopathology in some cases. These associations over 12 years could reflect enduring brain-behavior associations in spite of transactions with the environment, but could equally reflect processes in which dispositional differences in behavior influence the development of white matter. Future longitudinal studies are needed to resolve the causal nature of these sex-moderated associations., (© The Author(s) 2020.)

Objective: Impulsive decision-making is characterized by actions taken without considering consequences. Patients with Parkinson's disease (PD) who receive dopaminergic treatment, especially dopamine agonists, are at risk of developing impulsive-compulsive behaviors (ICBs). We assessed impulse-related changes across a large heterogeneous PD population using the Barratt impulsivity scale (BIS-11) by evaluating BIS-11 first- and second-order factors., Methods: We assessed a total of 204 subjects: 93 healthy controls (HCs), and 68 ICB- and 43 ICB + PD patients who completed the BIS-11. Using a general linear model and a least absolute shrinkage and selection operation regression, we compared BIS-11 scores between the HC, ICB- PD, and ICB + PD groups., Results: Patients with PD rated themselves as more impulsive than HCs in the BIS-11 total score, second-order attention domain, and first-order attention and self-control domains. ICB + patients recorded higher total scores as well as higher scores in the second-order non-planning domain and in self-control and cognitive complexity than ICB- patients., Interpretation: These results indicate that the patients with PD show particular problems with attentional control, whereas ICB + patients show a distinct problem in cognitive control and complexity. Additionally, it appears that all patients with PD are more impulsive than their age- and sex-matched healthy peers. Increased impulsivity may be a result of the disease course, or attributed to dopaminergic medication use, but these results emphasize the importance of the cognitive components of impulsivity in patients with PD., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures than traditional categorical diagnoses given its enhanced reliability. However, one complication is that observed biological correlates of clinical symptoms can reflect various factors, ranging from dispositional risk to consequences of psychopathology. In this paper, we argue that the HiTOP model provides an optimized framework for conducting research on the biological correlates of psychopathology from an ontogenetic perspective that distinguishes among indicators of liability, current symptoms, and consequences of illness. Through this approach, neurobiological research can contribute more effectively to identifying individuals at high dispositional risk, indexing treatment-related gains, and monitoring the consequences of mental illness, consistent with the aims of the HiTOP framework.
., (© 2019, AICHServier GroupCopyright © 2019 AICH Servier Group. All rights reserved.)

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer [18 F]fallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus and superior insula. These findings identify a link between a direct measure of mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Participants completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and nonhuman animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in interpreting PET findings as evidence that dopamine D2R loss is a primary cause of broad age-related declines in fluid cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

We present cortical surface parcellation using spherical deep convolutional neural networks. Traditional multi-atlas cortical surface parcellation requires inter-subject surface registration using geometric features with slow processing speed on a single subject (2-3 hours). Moreover, even optimal surface registration does not necessarily produce optimal cortical parcellation as parcel boundaries are not fully matched to the geometric features. In this context, a choice of training features is important for accurate cortical parcellation. To utilize the networks efficiently, we propose cortical parcellation-specific input data from an irregular and complicated structure of cortical surfaces. To this end, we align ground-truth cortical parcel boundaries and use their resulting deformation fields to generate new pairs of deformed geometric features and parcellation maps. To extend the capability of the networks, we then smoothly morph cortical geometric features and parcellation maps using the intermediate deformation fields. We validate our method on 427 adult brains for 49 labels. The experimental results show that our method outperforms traditional multi-atlas and naive spherical U-Net approaches, while achieving full cortical parcellation in less than a minute.

The dentate nucleus (DN) is a gray matter structure deep in the cerebellum involved in motor coordination, sensory input integration, executive planning, language, and visuospatial function. The DN is an emerging biomarker of disease, informing studies that advance pathophysiologic understanding of neurodegenerative and related disorders. The main challenge in defining the DN radiologically is that, like many deep gray matter structures, it has poor contrast in T1-weighted magnetic resonance (MR) images and therefore requires specialized MR acquisitions for visualization. Manual tracing of the DN across multiple acquisitions is resource-intensive and does not scale well to large datasets. We describe a technique that automatically segments the DN using deep learning (DL) on common imaging sequences, such as T1-weighted, T2-weighted, and diffusion MR imaging. We trained a DL algorithm that can automatically delineate the DN and provide an estimate of its volume. The automatic segmentation achieved higher agreement to the manual labels compared to template registration, which is the current common practice in DN segmentation or multiatlas segmentation of manual labels. Across all sequences, the FA maps achieved the highest mean Dice similarity coefficient (DSC) of 0.83 compared to T1 imaging ( DSC = 0.76 ), T2 imaging ( DSC = 0.79 ), or a multisequence approach ( DSC = 0.80 ). A single atlas registration approach using the spatially unbiased atlas template of the cerebellum and brainstem template achieved a DSC of 0.23, and multi-atlas segmentation achieved a DSC of 0.33. Overall, we propose a method of delineating the DN on clinical imaging that can reproduce manual labels with higher accuracy than current atlas-based tools., (© 2019 Society of Photo-Optical Instrumentation Engineers (SPIE).)

We previously hypothesized that the ubiquitous, but patterned correlations among all dimensions of psychopathology reflect a hierarchy of progressively more nonspecific causal influences, with a general factor of psychopathology-also dubbed the p factor-reflecting the most transdiagnostic causal influences. We further hypothesized that the general factor is a manifestation of individual differences in 1 or more trait-like dispositions, particularly negative emotionality, that are nonspecifically associated with risk for essentially every dimension of psychopathology. We tested the hypothesis that this and other dispositions measured in childhood/adolescence significantly predict general and specific second-order dimensions of psychopathology in early adulthood. The latent general factor of psychopathology itself was correlated over time from 10-17 to 23-31 years of age even though it was defined by different informants and different dimensions of symptoms. Using a measure of dispositions that minimizes item contamination with psychopathology symptoms, parent-rated negative emotionality in childhood and adolescence predicted the general factor of psychopathology based on self-reported symptoms in early adulthood, whereas parent-rated daring predicted the specific adult externalizing psychopathology factor after correction for multiple tests. In addition, youth-rated negative emotionality and daring predicted specific adult externalizing psychopathology. These results over a span of 12 years suggests that the general factor is relatively stable over time and that associations of dispositional traits with second-order dimensions of psychopathology are enduring, sometimes across informants. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [ 18 F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6-16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3-5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0-2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging., (© 2019 Wiley Periodicals, Inc.)

Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off- and on-dopamine agonist medication states to assess the effect of dopamine agonists on frontal cortical regional cerebral blood flow. Motor inhibition was measured by the Simon task in both medication states. We applied the dual process activation suppression model to dissociate fast response impulses from motor inhibition of incorrect responses. General linear regression model analyses determined the medication effect on regional cerebral blood flow and motor inhibition, and the relationship between regional cerebral blood flow and motor inhibitory proficiency. We show that dopamine agonist administration increases frontal cerebral blood flow, particularly in the pre-supplementary motor area (pre-SMA) and the dorsolateral prefrontal cortex (DLPFC). Higher regional blood flow in the pre-SMA, DLPFC and motor cortex was associated with better inhibitory control, suggesting that treatments which improve frontal cortical activity could ameliorate motor inhibition deficiency in PD patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is based on empirical patterns of co-occurrence among psychological symptoms. We highlight key ways in which this framework can advance mental-health research, and we provide some heuristics for using HiTOP to test theories of psychopathology. We then review emerging evidence that supports the value of a hierarchical, dimensional model of mental illness across diverse research areas in psychological science. These new data suggest that the HiTOP system has the potential to accelerate and improve research on mental-health problems as well as efforts to more effectively assess, prevent, and treat mental illness.

The relatively modest spatial resolution of positron emission tomography (PET) increases the likelihood of partial volume effects such that binding potential (BP ND ) may be underestimated. Given structural grey matter losses across adulthood, partial volume effects may be even more problematic in older age leading to overestimation of adult age differences. Here we examined the effects of partial volume correction (PVC) in two studies from different sites using different high-affinity D2-like radioligands (18 F-Fallypride, 11C-FLB457) and different PET camera resolutions (∼5 mm, 2.5 mm). Results across both data sets revealed that PVC increased estimated BP ND and reduced, though did not eliminate, age effects on BP ND . As expected, the effects of PVC were smaller in higher compared to lower resolution data. Analyses using uncorrected data that controlled for grey matter volume in each region of interest approximated PVC corrected data for some but not all regions. Overall, the findings suggest that PVC increases estimated BP ND in general and reduces adult age differences especially when using lower resolution cameras. The findings suggest that the past 30 years of research on dopamine receptor availability, for which very few studies use PVC, may overestimate effects of aging on dopamine receptor availability.

Obsessive compulsive disorder (OCD) is associated with altered processing in brain regions involved in conflict resolution. However, limited research has examined the extent to which conflict from emotional distracters characterizes OCD such that responsiveness to task-irrelevant emotional stimuli is altered compared to controls. In the present study, 16 patients with OCD and 15 healthy controls underwent functional magnetic resonance imaging (fMRI) during resolution of conflict from emotional or nonemotional distracters. Results in healthy controls demonstrated that rostral anterior cingulate cortex (rACC), middle frontal gyrus (MFG), and medial superior frontal gyrus (MSFG) showed greater activation for high conflict versus low conflict. Responses in these regions differed between the emotional and nonemotional distracter tasks, with rACC and MSFG having greater activation for conflict from nonemotional distracters and anterior MFG showing greater activation for conflict from emotional distracters. Furthermore, between-group differences revealed a region in right posterior MFG in which controls similarly exhibited greater activation during high conflict versus low conflict with emotional distracters; however, OCD patients showed the opposite pattern with greater activation during low conflict compared to high conflict. These findings suggest that activity of right posterior MFG may be relevant in better understanding inefficient responding during emotional conflict in OCD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rationale: Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed., Objectives: Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration., Methods: We used [ 18 F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBP ND , an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males., Results: Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control., Conclusions: While our finding in young adults from one dataset of greater %ΔBP ND in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.

Objectives: The ventrolateral prefrontal cortex (vlPFC) has been speculated to play an important role in complex processes that allow emotional factors to influence human cognition. Accumulating evidence from human neuroimaging studies, in conjunction with studies of patients with lesions and animal models, shed light on the role of the vlPFC in emotion regulation (ER). This review aims to discuss and integrate recent findings related to vlPFC's role in ER in the context of aging, drawing from diverse sources, and suggest future directions for research utilizing transcranial magnetic stimulation (TMS)., Methods/design: We summarize findings from the existing literature investigating the neural basis of frontal-lobe mediated ER and then highlight major findings from recent studies directly comparing healthy younger and older adult groups. We conclude by pointing to unaddressed questions worth pursuing in future research., Results and Discussion: We propose future research directions utilizing TMS to answer key unaddressed questions. Moreover, we discuss the potential advantages, challenges, and limitations of using TMS as a complement to the existing neuroimaging methods in ER., (© 2018 John Wiley & Sons, Ltd.)

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa. SIGNIFICANCE STATEMENT Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior., (Copyright © 2019 Castrellon et al.)

The emotional attentional blink (EAB) refers to a temporary impairment in the ability to identify a target when it is preceded by an emotional distractor. It is thought to occur because the emotional salience of the distractor exogenously captures attention for a brief duration, rendering the target unattended and preventing it from reaching awareness. Here we tested the extent to which the EAB can be attenuated by inducing a diffuse top-down attentional state, which has been shown to improve target identification in an analogous attentional phenomenon, the attentional blink. Rapid sequences of landscape images were presented centrally, and participants reported the orientation of a ± 90° rotation of a landscape target. To induce a diffuse state of attention, participants were given a secondary task of monitoring for the appearance of a colored dot in the periphery. We found that emotional distractors impaired target recognition performance to comparable extents, regardless of whether or not participants concurrently performed the peripheral-monitoring task. Moreover, we found that performance of the secondary task led to an impaired ability to ignore neutral distractors. Subjective ratings of target vividness mirrored the behavioral accuracy, with frequent reports of intermediate levels of vividness suggesting that the EAB might impair target visibility in a graded manner. Our results demonstrate that the EAB is robust to manipulations of top-down attention, suggesting that the temporary capture of attention by emotionally salient stimuli involves processes that are distinct from those that produce the attentional blink.

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories, ignoring the highly correlated nature of psychopathology. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of mental disorders, nearly all such studies used case-control designs, leaving it unclear whether observed relations reflect disorder-specific characteristics or transdiagnostic associations. Using a representative sample of 410 young adult twins oversampled for psychopathology risk, we tested the hypothesis that some previously observed relations between white matter microstructure properties in major tracts and specific disorders are related to second-order factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple statistical tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that some features of white matter within specific tracts may be transdiagnostically associated multiple forms of psychopathology through second-order factors of psychopathology rather with than individual mental disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)