[Show abstract][Hide abstract] ABSTRACT: The large impact of loss of reward on behavior has been well documented in adult populations. However, whether responsiveness to loss relative to gain is similarly elevated in child versus adult populations remains unclear. It is also unclear whether relations between incentive behaviors and self-reported reward/punishment sensitivity are similar within different developmental stages. To investigate these questions, 7- to 10-year-old children (N = 70) and young adults (N = 70) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, along with 2 probabilistic incentive tasks assessing gain approach and loss avoidance behavior. BIS/BAS subscales were calculated per Pagliaccio et al. (2015), which established an age invariant model of the BIS/BAS. Bias toward responses more frequently followed by gain feedback and away from responses more frequently followed by loss feedback, approach, and avoidance behavior, respectively, were quantified via signal detection statistics. Gain approach behavior did not differ across age groups; however, children exhibited significantly elevated loss avoidance relative to adults. Children also showed greater reductions in accuracy and slower RTs specifically following loss feedback relative to adults. Interestingly, despite age group differences in loss avoidance behavior, relations between self-report measures and approach/avoidance behaviors were similar across age groups. Participants reporting elevated motivation (BAS Drive) showed both elevated gain approach and elevated loss avoidance, with both types of behavior predicting unique variance in BAS Drive. Results highlight the often-neglected developmental and motivational roles of responsiveness to loss of reward. (PsycINFO Database Record
[Show abstract][Hide abstract] ABSTRACT: Goal maintenance is an aspect of cognitive control that has been identified as critical for understanding psychopathology according to criteria of the NIMH-sponsored CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) and Research Domain Criteria (RDoC) initiatives. CNTRICS proposed the expectancy AX-CPT, and its visual-spatial parallel the dot probe expectancy (DPX), as valid measures of the cognitive and neural processes thought to be relevant for goal maintenance. The goal of this study was to specifically examine the functional neural correlates and connectivity patterns of both goal maintenance tasks in the same subset of subjects to further validate their neural construct validity and clarify our understanding of the nature and function of the neural circuitry engaged by the tasks. Twenty-six healthy control subjects performed both the letter (AX) and dot pattern (DPX) variants of the CPT during fMRI. Behavioral performance was similar between tasks. The 2 tasks engaged the same brain networks including dorsolateral prefrontal cortex (DLPFC) and dorsal parietal regions, supporting their validity as complementary measures of the goal maintenance construct. Interestingly there was greater engagement of the frontal opercular insula region during the expectancy AX-CPT (letter) and greater functional connectivity between the PFC and medial temporal lobe in the DPX (dot pattern). These differences are consistent with differential recruitment of phonological and visual-spatial processes by the two tasks and suggest that additional long-term memory systems may be engaged by the dot probe version.
[Show abstract][Hide abstract] ABSTRACT: Previous work suggests that individuals with schizophrenia display accelerated aging of white matter integrity, however, it is still unknown whether functional brain networks also decline at an elevated rate in schizophrenia. Given the known degradation of functional connectivity and the normal decline in cognitive functioning throughout healthy aging, we aimed to test the hypothesis that efficiency of large-scale functional brain networks supporting overall cognition, as well as integrity of hub nodes within those networks, show evidence of accelerated aging in schizophrenia. Using pseudo-resting state data in 54 healthy controls and 46 schizophrenia patients, in which task-dependent signal from 3 tasks was regressed out to approximate resting-state data, we observed a significant diagnosis by age interaction in the prediction of both global and local efficiency of the cingulo-opercular network, and of the local efficiency of the fronto-parietal network, but no interaction when predicting both default mode network and whole brain efficiency. We also observed a significant diagnosis by age interaction for the node degree of the right anterior insula, left dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. All interactions were driven by stronger negative associations between age and network metrics in the schizophrenia group than the healthy controls. These data provide evidence that is consistent with accelerated aging of large-scale functional brain networks in schizophrenia that support higher-order cognitive ability.
[Show abstract][Hide abstract] ABSTRACT: Previous work suggests that individuals with schizophrenia display accelerated aging of white matter integrity, however it is still unknown whether functional brain networks also decline at an elevated rate in schizophrenia. Given the known degradation of functional connectivity and the normal decline in cognitive functioning throughout healthy aging, we aimed to test the hypothesis that efficiency of large-scale functional brain networks supporting overall cognition, as well as integrity of hub nodes within those networks, show evidence of accelerated aging in schizophrenia. Using pseudo-resting state data in 54 healthy controls and 46 schizophrenia patients, in which task-dependent signal from three tasks was regressed out to approximate resting-state data, we observed a significant diagnosis by age interaction in the prediction of both global and local efficiency of the cingulo-opercular network, and of the local efficiency of the fronto-parietal network, but no interaction when predicting both default mode network and whole brain efficiency. We also observed a significant diagnosis by age interaction for the node degree of the right anterior insula, left dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. All interactions were driven by stronger negative associations between age and network metrics in the schizophrenia group than the healthy controls. These data provide evidence that is consistent with accelerated aging of large-scale functional brain networks in schizophrenia that support higher-order cognitive ability.
[Show abstract][Hide abstract] ABSTRACT: Investigating brain tissue T2* relaxation properties in vivo can potentially guide the uncovering of neuropathology in psychiatric illness, which is traditionally examined post mortem. We use an MRI-based Gradient Echo Plural Contrast Imaging (GEPCI) technique that produces inherently co-registered images allowing quantitative assessment of tissue cellular and hemodynamic properties. Usually described as R2* (=1/T2*) relaxation rate constant, recent developments in GEPCI allow the separation of cellular-specific (R2*C) and hemodynamic (BOLD) contributions to the MRI signal decay. We characterize BOLD effect in terms of tissue concentration of deoxyhemoglobin, i.e. CDEOXY, which reflects brain activity. 17 control (CON), 17 bipolar disorder (BPD), 16 schizophrenia (SCZ), and 12 unaffected schizophrenia sibling (SIB) participants were scanned and post-processed using GEPCI protocols. A MANOVA of 38gray matter regions ROIs showed significant group effects for CDEOXY but not for R2*C. In the three non-control groups, 71-92% of brain regions had increased CDEOXY. Group effects were observed in the superior temporal cortex and the thalamus. Increased superior temporal cortex CDEOXY was found in SCZ (p=0.01), BPD (p=0.01) and SIB (p=0.02), with bilateral effects in SCZ and only left hemisphere effects in BPD and SIB. Thalamic CDEOXY abnormalities were observed in SCZ (p=0.003), BPD (p=0.03) and SIB (p=0.02). Our results suggest that increased activity in certain brain regions is part of the underlying pathophysiology of specific psychiatric disorders. High CDEOXY in the superior temporal cortex suggests abnormal activity with auditory, language and/or social cognitive processing. Larger studies are needed to clarify the clinical significance of relaxometric abnormalities.
Schizophrenia Research 10/2015; DOI:10.1016/j.schres.2015.10.004 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the relationship between individual subjects' functional connectomes and 280 behavioral and demographic measures in a single holistic multivariate analysis relating imaging to non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Despite research documenting the existence of depression and other psychiatric disorders in early childhood, little is known about the nature and consequences of suicidal cognitions and behaviors (SI) in young children ages 3 to 7 years. The identification of trajectories of SI across childhood is a critical step toward preventing childhood suicide.
Participants were 306 children enrolled in a prospective longitudinal investigation of young children and their families. Children and their families completed a baseline assessment between ages 3 and 7 years, and at least 1 follow-up assessment (ages 7-12 years). Child psychopathology, suicidal thoughts, plans, and behaviors were assessed via parent and trained interviewer report before age 9, and also with self-report after age 9. Data on maternal history of psychopathology, as well as maternal and family history of suicide attempts, were also obtained through parent report.
Controlling for a range of clinical and demographic variables, early-childhood SI (as defined as suicidal thoughts, behavior, or any expression of plans/attempts occurring before age 7) and suicidal themes in play were concurrently associated with childhood attention-deficit/hyperactivity (ADHD) and oppositional defiant/conduct disorders (ODD/CD). Early-childhood SI also predicted school-age depression and ODD/CD; however, these findings were no longer significant after controlling for the same diagnoses at the childhood baseline. Longitudinal analysis indicated that early-childhood SI was a robust predictor of school-age SI, even after accounting for psychiatric disorders at both time points.
Extending current research, these findings demonstrate that early-childhood SI confers significant risk for continuation into school-age SI and is concurrently associated with ADHD and ODD/CD. Although the meaning of early-childhood SI remains unclear, results suggest that it is a clinically important phenomenon that should be carefully assessed and taken seriously as a marker of risk for ongoing suicidal ideation/behavior. These findings suggest that early screening for SI in childhood is indicated in clinical settings, particularly in children less than 7 years of age with depression and externalizing disorders.
Journal of the American Academy of Child and Adolescent Psychiatry 09/2015; 54(11). DOI:10.1016/j.jaac.2015.08.009 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use.
To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations.
Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime).
Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs.
Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003).
In this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.
[Show abstract][Hide abstract] ABSTRACT: 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. (PsycINFO Database Record
(c) 2015 APA, all rights reserved).
[Show abstract][Hide abstract] ABSTRACT: Individuals with schizophrenia can encode item-specific information to support familiarity-based recognition but are disproportionately impaired encoding interitem relationships (relational encoding) and recollecting information. The Relational and Item-Specific Encoding (RiSE) paradigm has been used to disentangle these encoding and retrieval processes, which may depend on specific medial temporal lobe (MTL) and prefrontal cortex (PFC) subregions. Functional magnetic resonance (fMRI) imaging during RiSE task performance could help to specify dysfunctional neural circuits in schizophrenia that can be targeted for interventions to improve memory and functioning in the illness.
To use fMRI to test the hypothesis that schizophrenia disproportionately affects MTL and PFC subregions during relational encoding and retrieval relative to item-specific memory processes, and to use fMRI results from healthy individuals serving as controls to establish neural construct validity for RiSE.
This multisite, case-control, cross-sectional fMRI study was conducted between November 1, 2010, and May 30, 2012, at 5 Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia sites. The final sample included 52 outpatients with clinically stable schizophrenia and 57 demographically matched healthy control participants. Data analysis was performed between February 1, 2013, and May 30, 2014.
Behavioral performance speed and accuracy (d') on item recognition and associative recognition tasks. Voxelwise statistical parametric maps for a priori MTL and PFC regions of interest to test activation differences between relational and item-specific memory during encoding and retrieval.
Item recognition was disproportionately impaired in patients with schizophrenia relative to healthy control participants following relational encoding (F1,107 = 4.7; P = .03). The differential deficit was accompanied by reduced dorsolateral PFC activation during relational encoding in patients with schizophrenia compared with healthy control participants (z > 2.3; P < .05 corrected). Retrieval success (hits > misses) was associated with hippocampal activation in healthy control participants during relational item recognition and associative recognition conditions, and hippocampal activation was specifically reduced in schizophrenia for recognition of relational but not item-specific information (z > 2.3; P < .05 corrected).
In this unique, multisite fMRI study, results in the healthy control group supported RiSE construct validity by revealing expected memory effects in PFC and MTL subregions during encoding and retrieval. Comparison of schizophrenic and healthy control participants revealed disproportionate memory deficits in schizophrenia for relational vs item-specific information, accompanied by regionally and functionally specific deficits in dorsolateral PFC and hippocampal activation.
[Show abstract][Hide abstract] ABSTRACT: Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials.
Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2015.