Dataset Information

Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

ABSTRACT: OBJECTIVE:Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age. METHOD:The authors studied a transdiagnostic sample of 195 youths with varying levels of irritability (disruptive mood dysregulation disorder, N=52; anxiety disorder, N=42; attention deficit hyperactivity disorder, N=40; and healthy volunteers, N=61). Irritability was measured by parent and child reports on the Affective Reactivity Index. The fMRI paradigm was a cued-attention task differentiating neural activity in response to frustration (rigged feedback) from activity during attention orienting in the trial following frustration. RESULTS:Whole-brain activation analyses revealed associations with irritability during attention orienting following frustration. Irritability was positively associated with frontal-striatal activation, specifically in the dorsolateral prefrontal cortex, inferior frontal gyrus, and caudate. Age moderated the association between irritability and activation in some frontal and posterior regions (the anterior cingulate cortex, medial frontal gyrus, cuneus, precuneus, and superior parietal lobule [F=19.04-28.51, df=1, 189, partial eta squared=0.09-0.13]). Specifically, higher irritability was more strongly related to increased activation in younger youths compared with older youths. CONCLUSIONS:Following frustration, levels of irritability correlated with activity in neural systems mediating attention orienting, top-down regulation of emotions, and motor execution. Although most associations were independent of age, dysfunction in the anterior cingulate cortex and posterior regions was more pronounced in young children with irritability.

SUBMITTER: Tseng WL

PROVIDER: S-EPMC6408218 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

Tseng Wan-Ling WL Deveney Christen M CM Stoddard Joel J Kircanski Katharina K Frackman Anna E AE Yi Jennifer Y JY Hsu Derek D Moroney Elizabeth E Machlin Laura L Donahue Laura L Roule Alexandra A Perhamus Gretchen G Reynolds Richard C RC Roberson-Nay Roxann R Hettema John M JM Towbin Kenneth E KE Stringaris Argyris A Pine Daniel S DS Brotman Melissa A MA Leibenluft Ellen E

The American journal of psychiatry 20181019 1

<h4>Objective</h4>Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age.<h4>M ...[more]

PMID: 30336704

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Project description:BackgroundIrritability is a common and impairing occurrence in autistic youth, yet the underlying mechanisms are not well-known. In typically developing populations, differences in frustration response have been suggested as important driver of the behavioural symptoms of irritability. Research exploring the role of frustration response as a risk factor for irritability in autistic populations is limited and often uses parent report or observer ratings; objective measures of frustration response appropriate for use in autistic populations are required to advance the field.MethodsIn the current study, fifty-two autistic adolescents aged 13-17 years from a population-based longitudinal study completed an experimental task designed to induce frustration through exposure to periods of unexpected delay. Behavioural (number of button presses) and physiological (heart rate; HR) metrics were collected during delay periods. Irritability was measured using the parent-rated Affective Reactivity Index (ARI). Analyses used mixed-level models to test whether irritability was associated with different slopes of behavioural and physiological response to experimentally induced frustration during the task. Age and baseline HR (for the physiological data only) were included as covariates.ResultsAnalyses showed a marginal association between irritability and the slope of behavioural response (incident rate ratio (IRR) =.98, p=.06), and a significant association with the slope of physiological response (b=-.10, p=.04); higher levels of irritability were associated with a dampened behavioural and physiological response, as indicated by flatter slopes of change over the course of the task. The pattern of results largely remained in sensitivity analyses, although the association with physiological response became non-significant when adjusting for IQ, autism symptom severity, and medication use (b=-.10, p=.10).ConclusionsResults suggest that the current experimental task may be a useful objective measure of frustration response for use with autistic populations, and that a non-adaptive response to frustration may be one biological mechanism underpinning irritability in autistic youth. This may represent an important target for future intervention studies.

Project description:ImportancePsychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology.ObjectiveTo determine shared and unique effects of 2 major dimensions of child psychopathology, irritability and anxiety, on neural responses to facial emotions during functional magnetic resonance imaging.Design, setting, and participantsCross-sectional functional magnetic resonance imaging study in a large, well-characterized clinical sample at a research clinic at the National Institute of Mental Health. The referred sample included youths ages 8 to 17 years, 93 youths with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders and 22 healthy youths.Main outcomes and measuresThe child's irritability and anxiety were rated by both parent and child on the Affective Reactivity Index and Screen for Child Anxiety Related Disorders, respectively. Using functional magnetic resonance imaging, neural response was measured across the brain during gender labeling of varying intensities of angry, happy, or fearful face emotions. In mixed-effects analyses, the shared and unique effects of irritability and anxiety were tested on amygdala functional connectivity and activation to face emotions.ResultsThe mean (SD) age of participants was 13.2 (2.6) years; of the 115 included, 64 were male. Irritability and/or anxiety influenced amygdala connectivity to the prefrontal and temporal cortex. Specifically, irritability and anxiety jointly influenced left amygdala to left medial prefrontal cortex connectivity during face emotion viewing (F4,888 = 9.20; P < .001 for mixed model term). During viewing of intensely angry faces, decreased connectivity was associated with high levels of both anxiety and irritability, whereas increased connectivity was associated with high levels of anxiety but low levels of irritability (Wald χ21 = 21.3; P < .001 for contrast). Irritability was associated with differences in neural response to face emotions in several areas (F2, 888 ≥ 13.45; all P < .001). This primarily occurred in the ventral visual areas, with a positive association to angry and happy faces relative to fearful faces.Conclusions and relevanceThese data extend prior work conducted in youths with irritability or anxiety alone and suggest that research may miss important findings if the pathophysiology of irritability and anxiety are studied in isolation. Decreased amygdala-medial prefrontal cortex connectivity may mediate emotion dysregulation when very anxious and irritable youth process threat-related faces. Activation in the ventral visual circuitry suggests a mechanism through which signals of social approach (ie, happy and angry expressions) may capture attention in irritable youth.

Project description:IntroductionAttention-deficit hyperactive disorder (ADHD) is the most common neurodevelopmental disorder in children. Diagnosis is currently based on behavioral criteria, but magnetic resonance imaging (MRI) of the brain is increasingly used in ADHD research. To date however, MRI studies have provided mixed results in ADHD patients, particularly with respect to the laterality of findings.MethodsWe studied 849 children and adolescents (ages 6-21 y.o.) diagnosed with ADHD (n = 341) and age-matched typically developing (TD) controls with structural brain MRI. We calculated volumetric measures from 34 cortical and 14 non-cortical brain regions per hemisphere, and detailed shape morphometry of subcortical nuclei. Diffusion tensor imaging (DTI) data were collected for a subset of 104 subjects; from these, we calculated mean diffusivity and fractional anisotropy of white matter tracts. Group comparisons were made for within-hemisphere (right/left) and between hemisphere asymmetry indices (AI) for each measure.ResultsDTI mean diffusivity AI group differences were significant in cingulum, inferior and superior longitudinal fasciculus, and cortico-spinal tracts (p < 0.001) with the effect of stimulant treatment tending to reduce these patterns of asymmetry differences. Gray matter volumes were more asymmetric in medication free ADHD individuals compared to TD in twelve cortical regions and two non-cortical volumes studied (p < 0.05). Morphometric analyses revealed that caudate, hippocampus, thalamus, and amygdala were more asymmetric (p < 0.0001) in ADHD individuals compared to TD, and that asymmetry differences were more significant than lateralized comparisons.ConclusionsBrain asymmetry measures allow each individual to serve as their own control, diminishing variability between individuals and when pooling data across sites. Asymmetry group differences were more significant than lateralized comparisons between ADHD and TD subjects across morphometric, volumetric, and DTI comparisons.

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Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

Publications

Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.

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