Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in rewa... more Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Method: Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy co...
Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developin... more Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing depression. The neurobiological substrates that convey this risk remain poorly understood. On the basis of considerable data implicating hippocampal abnormalities in depressive disorders, we aimed to explore the relationship between the hippocampus and levels of depressive symptomatology in ADHD. We used magnetic resonance imaging (MRI) to examine the volumes and resting-state functional connectivity of the hippocampus in a sample of 32 medication naive children with ADHD (ages 6 - 13) and 33 age- and sex-matched healthy control (HC) participants. Compared with the HC participants, the participants with ADHD had (i) reduced volumes of the left hippocampus and (ii) reduced functional connectivity between the left hippocampus and the left orbitofrontal cortex (OFC); these hippocampal effects were associated with more severe depressive symptoms, even after controlling for the severity of inattentive and hyperactive/impulsive symptoms. Altered hippocampal structure and connectivity were not associated with anxiety or more general internalizing symptoms. Though preliminary, these findings suggest that the relationship between hippocampal anomalies and ADHD youth's susceptibility to developing depression and other mood disorders may merit further investigation with follow-up longitudinal research.
Current neurocognitive models of attention-deficit/hyperactivity disorder (ADHD) suggest that neu... more Current neurocognitive models of attention-deficit/hyperactivity disorder (ADHD) suggest that neural circuits involving both attentional and affective processing make independent contributions to the phenomenology of the disorder. However, a clear dissociation of attentional and affective circuits and their behavioral correlates has yet to be shown in medication-naïve children with ADHD. Using resting-state functional connectivity MRI (rs-fcMRI) in a cohort of medication naïve children with (N=22) and without (N=20) ADHD, we demonstrate that children with ADHD have reduced connectivity in two neural circuits: one underlying executive attention (EA) and the other emotional regulation (ER). We also demonstrate a double dissociation between these two neural circuits and their behavioral correlates such that reduced connectivity in the EA circuit correlates with executive attention deficits but not with emotional lability, while on the other hand, reduced connectivity in the ER circuit correlates with emotional lability but not with executive attention deficits. These findings suggest potential avenues for future research such as examining treatment effects on these two neural circuits as well as the potential prognostic and developmental significance of disturbances in one circuit vs the other.
Developmental stuttering is a disorder of speech fluency with an unknown pathogenesis. The simila... more Developmental stuttering is a disorder of speech fluency with an unknown pathogenesis. The similarity of its phenotype and natural history with other childhood neuropsychiatric disorders of frontostriatal pathology suggests that stuttering may have a closely related pathogenesis. We investigated in this study the potential involvement of frontostriatal circuits in developmental stuttering. We collected functional magnetic resonance imaging data from 46 persons with stuttering and 52 fluent controls during performance of the Simon Spatial Incompatibility Task. We examined differences between the two groups of blood-oxygen-level-dependent activation associated with two neural processes, the resolution of cognitive conflict and the context-dependent adaptation to changes in conflict. Stuttering speakers and controls did not differ on behavioral performance on the task. In the presence of conflict-laden stimuli, however, stuttering speakers activated more strongly the cingulate cortex, left anterior prefrontal cortex, right medial frontal cortex, left supplementary motor area, right caudate nucleus, and left parietal cortex. The magnitude of activation in the anterior cingulate cortex correlated inversely in stuttering speakers with symptom severity. Stuttering speakers also showed blunted activation during context-dependent adaptation in the left dorsolateral prefrontal cortex, a brain region that mediates cross-temporal contingencies. Frontostriatal hyper-responsivity to conflict resembles prior findings in other disorders of frontostriatal pathology, and therefore likely represents a general mechanism supporting functional compensation for an underlying inefficiency of neural processing in these circuits. The reduced activation of dorsolateral prefrontal cortex likely represents the inadequate readiness of stuttering speakers to execute a sequence of motor responses.
To address large uncertainties in current cloud retrievals, a multi-year cloud retrieval dataset ... more To address large uncertainties in current cloud retrievals, a multi-year cloud retrieval dataset is being created by assembling existing Atmospheric Radiation Measurements program (ARM) cloud data retrieved from using multiple cloud retrieval algorithms. Individual cloud retrieval data are being reorganized onto a uniform temporal and spatial grid for easy use by climate modelers. Currently, total 7 different cloud retrievals over many years are included in the dataset with 3 or 4 different retrievals available for each of the five ARM permanent research sites: SGP, NSA, and TWP-C1 (Manus), C2 (Nauru), and C3 (Darwin). In this paper, we will provide an overview of the cloud property ensemble dataset, demonstrate the value of the ensemble cloud retrieval data product, and present results from initial analysis of the different cloud retrievals.
Journal of the American Academy of Child & Adolescent Psychiatry, 2011
Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hype... more Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hyperactivity disorder (ADHD). We aimed to identify neural substrates associated with emotional reactivity and to assess the effects of stimulants on those substrates. We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (n = 15) and without (n = 15) ADHD while they performed a task involving the subliminal presentation of fearful faces. Using dynamic causal modeling, we also examined the effective connectivity of two regions associated with emotional reactivity, i.e., the amygdala and the lateral prefrontal cortex (LPFC). The participants with ADHD underwent scanning both on and off stimulant medication in a counterbalanced fashion. During the task, we found that activity in the right amygdala was greater in adolescents with ADHD than in control subjects. In addition, in adolescents with ADHD, greater connectivity was detected between the amygdala and LPFC. Stimulants had a normalizing effect on both the activity in the right amygdala and the connectivity between the amygdala and LPFC. Our findings demonstrate that in adolescents with ADHD, a neural substrate of fear processing is atypical, as is the connectivity between the amygdala and LPFC. These findings suggest possible neural substrates for the emotional reactivity that is often present in youths with ADHD, and provide putative neural targets for the development of novel therapeutic interventions for this condition.
Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in rewa... more Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Method: Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy co...
Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developin... more Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing depression. The neurobiological substrates that convey this risk remain poorly understood. On the basis of considerable data implicating hippocampal abnormalities in depressive disorders, we aimed to explore the relationship between the hippocampus and levels of depressive symptomatology in ADHD. We used magnetic resonance imaging (MRI) to examine the volumes and resting-state functional connectivity of the hippocampus in a sample of 32 medication naive children with ADHD (ages 6 - 13) and 33 age- and sex-matched healthy control (HC) participants. Compared with the HC participants, the participants with ADHD had (i) reduced volumes of the left hippocampus and (ii) reduced functional connectivity between the left hippocampus and the left orbitofrontal cortex (OFC); these hippocampal effects were associated with more severe depressive symptoms, even after controlling for the severity of inattentive and hyperactive/impulsive symptoms. Altered hippocampal structure and connectivity were not associated with anxiety or more general internalizing symptoms. Though preliminary, these findings suggest that the relationship between hippocampal anomalies and ADHD youth's susceptibility to developing depression and other mood disorders may merit further investigation with follow-up longitudinal research.
Current neurocognitive models of attention-deficit/hyperactivity disorder (ADHD) suggest that neu... more Current neurocognitive models of attention-deficit/hyperactivity disorder (ADHD) suggest that neural circuits involving both attentional and affective processing make independent contributions to the phenomenology of the disorder. However, a clear dissociation of attentional and affective circuits and their behavioral correlates has yet to be shown in medication-naïve children with ADHD. Using resting-state functional connectivity MRI (rs-fcMRI) in a cohort of medication naïve children with (N=22) and without (N=20) ADHD, we demonstrate that children with ADHD have reduced connectivity in two neural circuits: one underlying executive attention (EA) and the other emotional regulation (ER). We also demonstrate a double dissociation between these two neural circuits and their behavioral correlates such that reduced connectivity in the EA circuit correlates with executive attention deficits but not with emotional lability, while on the other hand, reduced connectivity in the ER circuit correlates with emotional lability but not with executive attention deficits. These findings suggest potential avenues for future research such as examining treatment effects on these two neural circuits as well as the potential prognostic and developmental significance of disturbances in one circuit vs the other.
Developmental stuttering is a disorder of speech fluency with an unknown pathogenesis. The simila... more Developmental stuttering is a disorder of speech fluency with an unknown pathogenesis. The similarity of its phenotype and natural history with other childhood neuropsychiatric disorders of frontostriatal pathology suggests that stuttering may have a closely related pathogenesis. We investigated in this study the potential involvement of frontostriatal circuits in developmental stuttering. We collected functional magnetic resonance imaging data from 46 persons with stuttering and 52 fluent controls during performance of the Simon Spatial Incompatibility Task. We examined differences between the two groups of blood-oxygen-level-dependent activation associated with two neural processes, the resolution of cognitive conflict and the context-dependent adaptation to changes in conflict. Stuttering speakers and controls did not differ on behavioral performance on the task. In the presence of conflict-laden stimuli, however, stuttering speakers activated more strongly the cingulate cortex, left anterior prefrontal cortex, right medial frontal cortex, left supplementary motor area, right caudate nucleus, and left parietal cortex. The magnitude of activation in the anterior cingulate cortex correlated inversely in stuttering speakers with symptom severity. Stuttering speakers also showed blunted activation during context-dependent adaptation in the left dorsolateral prefrontal cortex, a brain region that mediates cross-temporal contingencies. Frontostriatal hyper-responsivity to conflict resembles prior findings in other disorders of frontostriatal pathology, and therefore likely represents a general mechanism supporting functional compensation for an underlying inefficiency of neural processing in these circuits. The reduced activation of dorsolateral prefrontal cortex likely represents the inadequate readiness of stuttering speakers to execute a sequence of motor responses.
To address large uncertainties in current cloud retrievals, a multi-year cloud retrieval dataset ... more To address large uncertainties in current cloud retrievals, a multi-year cloud retrieval dataset is being created by assembling existing Atmospheric Radiation Measurements program (ARM) cloud data retrieved from using multiple cloud retrieval algorithms. Individual cloud retrieval data are being reorganized onto a uniform temporal and spatial grid for easy use by climate modelers. Currently, total 7 different cloud retrievals over many years are included in the dataset with 3 or 4 different retrievals available for each of the five ARM permanent research sites: SGP, NSA, and TWP-C1 (Manus), C2 (Nauru), and C3 (Darwin). In this paper, we will provide an overview of the cloud property ensemble dataset, demonstrate the value of the ensemble cloud retrieval data product, and present results from initial analysis of the different cloud retrievals.
Journal of the American Academy of Child & Adolescent Psychiatry, 2011
Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hype... more Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hyperactivity disorder (ADHD). We aimed to identify neural substrates associated with emotional reactivity and to assess the effects of stimulants on those substrates. We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (n = 15) and without (n = 15) ADHD while they performed a task involving the subliminal presentation of fearful faces. Using dynamic causal modeling, we also examined the effective connectivity of two regions associated with emotional reactivity, i.e., the amygdala and the lateral prefrontal cortex (LPFC). The participants with ADHD underwent scanning both on and off stimulant medication in a counterbalanced fashion. During the task, we found that activity in the right amygdala was greater in adolescents with ADHD than in control subjects. In addition, in adolescents with ADHD, greater connectivity was detected between the amygdala and LPFC. Stimulants had a normalizing effect on both the activity in the right amygdala and the connectivity between the amygdala and LPFC. Our findings demonstrate that in adolescents with ADHD, a neural substrate of fear processing is atypical, as is the connectivity between the amygdala and LPFC. These findings suggest possible neural substrates for the emotional reactivity that is often present in youths with ADHD, and provide putative neural targets for the development of novel therapeutic interventions for this condition.
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Papers by Zhishun Wang