Motivational and hedonic impairments are core aspects of a variety of types of psychopathology. These impairments cut across diagnostic categories and may be critical to understanding major aspects ...of the functional impairments accompanying psychopathology. Given the centrality of motivational and hedonic systems to psychopathology, the Research Domain Criteria (RDoC) initiative includes a "positive valence" systems domain that outlines a number of constructs that may be key to understanding the nature and mechanisms of motivational and hedonic impairments in psychopathology. These component constructs include initial responsiveness to reward, reward anticipation or expectancy, incentive or reinforcement learning, effort valuation, and action selection. Here, we review behavioral and neuroimaging studies providing evidence for impairments in these constructs in individuals with psychosis versus in individuals with depressive pathology. There are important differences in the nature of reward-related and hedonic deficits associated with psychosis versus depression that have major implications for our understanding of etiology and treatment development. In particular, the literature strongly suggests the presence of impairments in in-the-moment hedonics or "liking" in individuals with depressive pathology, particularly among those who experience anhedonia. Such deficits may propagate forward and contribute to impairments in other constructs that are dependent on hedonic responses, such as anticipation, learning, effort, and action selection. Such hedonic impairments could reflect alterations in dopamine and/or opioid signaling in the striatum related to depression or specifically to anhedonia in depressed populations. In contrast, the literature points to relatively intact in-the-moment hedonic processing in psychosis, but provides much evidence for impairments in other components involved in translating reward to action selection. Particularly, individuals with schizophrenia exhibit altered reward prediction and associated striatal and prefrontal activation, impaired reward learning, and impaired reward-modulated action selection.
Maternal major depressive disorder (MDD) increases risk for MDD and predicts reduced reward responding in adolescent offspring. However, it is unclear whether alterations in neural response to reward ...can be detected in school-aged children at high risk before the typical increase in reward response observed in adolescence.
To assess relationships between neural response to gain/loss feedback, MDD risk, and child depressive symptoms, 47 psychiatrically healthy 7- to 10-year-old children (16 at high risk given maternal MDD) completed questionnaires and a functional magnetic resonance imaging (fMRI) card-guessing game in which candy was gained and lost.
High-risk children showed both blunted response to gain and greater deactivation/reduced activation to loss within the ventral striatum and anterior insula. Within the striatum, risk-group differences in response to loss feedback were significantly larger than for gain, with greater deactivation to loss predicting risk-group status above and beyond blunted gain activation. Anhedonia was related to reduced deactivation to loss (i.e., reduced sensitivity to loss), whereas negative mood was related to enhanced deactivation to loss (i.e., enhanced sensitivity to loss) in the ventral striatum.
High-risk children showed blunted ventral striatal activation to gain feedback, but ventral striatal deactivation to loss was a stronger predictor of MDD risk. Furthermore, relationships between response to loss and elevated depressive symptoms within the ventral striatum and cingulate differed depending on the type of depressive symptom. Together these results highlight the potentially important role of response to loss of reward in childhood risk for depression.
Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that ...more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.
Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; ...however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items.
•Large HRF shape heterogeneity exists across the brain, individuals, conditions, and groups.•Canonical HRF may suffer from under-fitting and information loss.•We propose an HRF estimation approach ...for both individual and population levels.•We demonstrate that inferential efficiency can be substantially improved through a constraint on the HRF smoothness.•Our HRF estimation approach also revealed evidence for the whole-brain BOLD fluctuations.•We offer recommendations for adopting the HRF estimation approach in experimental design and modeling practice.
Typical fMRI analyses often assume a canonical hemodynamic response function (HRF) that primarily focuses on the peak height of the overshoot, neglecting other morphological aspects. Consequently, reported analyses often reduce the overall response curve to a single scalar value. In this study, we take a data-driven approach to HRF estimation at the whole-brain voxel level, without assuming a response profile at the individual level. We then employ a roughness penalty at the population level to estimate the response curve, aiming to enhance predictive accuracy, inferential efficiency, and cross-study reproducibility. By examining a fast event-related FMRI dataset, we demonstrate the shortcomings and information loss associated with adopting the canonical approach. Furthermore, we address the following key questions: 1) To what extent does the HRF shape vary across different regions, conditions, and participant groups? 2) Does the data-driven approach improve detection sensitivity compared to the canonical approach? 3) Can analyzing the HRF shape help validate the presence of an effect in conjunction with statistical evidence? 4) Does analyzing the HRF shape offer evidence for whole-brain response during a simple task?
Background
Based on findings from adults with obsessive‐compulsive disorder (OCD), this study examined alterations in resting‐state functional connectivity (rs‐fc) between the basolateral amygdala ...(BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA‐vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first‐line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning—a probable mechanism of action of E/RP.
Methods
Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment‐naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age‐ and sex‐matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12–16‐week E/RP intervention for OCD. Participants were rescanned after the 12–16‐week period. ANCOVAs tested group differences in baseline rs‐fc. Cross‐lagged panel models examined relationships between BLA‐vmPFC rs‐fc and OCD symptoms pre‐ and posttreatment. All tests were adjusted for participants' age, sex, and head motion.
Results
Right BLA‐vmPFC rs‐fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA‐vmPFC rs‐fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA‐vmPFC rs‐fc was unassociated with change in OCD symptoms pre‐ to posttreatment.
Conclusions
These results provide further evidence of the BLA‐vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.
Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research ...suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, known as imaging gene x environment interaction (iGxE), is beginning to contribute to our understanding of the neural mechanisms through which genetic variation and stress increase psychopathology risk. Although awaiting replication, evidence suggests that genetic variation within the canonical neuroendocrine stress hormone system, the hypothalamic-pituitary-adrenal axis, contributes to variability in stress-related corticolimbic structure and function, which, in turn, confers risk for psychopathology. For iGxE research to reach its full potential it will have to address many challenges, of which we discuss: (i) small effects, (ii) measuring the environment and neural phenotypes, (iii) the absence of detailed mechanisms, and (iv) incorporating development. By actively addressing these challenges, iGxE research is poised to help identify the neural mechanisms underlying genetic and environmental associations with psychopathology.
Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings ...suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).
We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7−25-year-olds (Mage = 15.80). Linear regression evaluated FP-DMN associations with IQ.
We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.
FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.
•Prenatal environmental tobacco smoke (ETS) increases risk for attention problems.•The neurobiological effects of prenatal ETS are unknown.•Prenatal ETS alters the structure and function of ...frontostriatal control circuitry.•Smaller thalamic volume mediated effects of exposure on attention problems.•ETS and smoking in pregnancy confer similar risk on brain structure and behavior.
Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children’s brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children’s cognitive control circuitry and behavior.
Forty-one children (7–9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist.
Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen’s D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05).
Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren’s neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.
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