Linking ADHD to the Neural Circuitry of Attention

Mueller, Adrienne; Hong, David S.; Shepard, Steven B.; Moore, Tirin

doi:10.1016/j.tics.2017.03.009

Cited by 127 publications

(125 citation statements)

References 161 publications

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“…Our analyses support the current literature, with a focus on Crus I and Crus II, which are considered part of an executive control network (Stoodley, 2012). Executive function deficits are known to be a key problem in ADHD (Mahone and Denckla, 2017;Mueller et al, 2017) and have been related to inattention symptoms (Chhabildas et al, 2001;Neely et al, 2016;Nigg et al, 2005;Willcutt et al, 2005).…”

Section: Discussionsupporting

confidence: 83%

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Jiang¹,

Duan

Rootes-Murdy³

et al. 2019

Preprint

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AbstractGray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 – 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a case/control difference with sub-clinical cases being intermediate between cases and controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to cases, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.

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Section: Discussionsupporting

confidence: 83%

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Jiang¹,

Duan

Rootes-Murdy³

et al. 2019

Preprint

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“…Clinically, there is strong interindividual variation in psychiatric and somatic comorbidities across the lifespan (5). Most individuals with ADHD have deficits in one or more cognitive domains, but there is substantial overlap between ADHD and controls (6)(7)(8). The estimated heritability of ADHD is 70-80%;…”

Section: Introductionmentioning

confidence: 99%

Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Rooij

Mota

et al. 2019

Preprint

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Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in children and adults. Neuroanatomic heterogeneity limits our understanding of the etiology of ADHD. This study aimed to parse neuroanatomic heterogeneity of ADHD, and to determine whether subgroups could be discerned in patients based on subcortical volumes. Methods:Using the dataset from the ENIGMA-ADHD Working Group, we applied exploratory factor analysis (EFA) to subcortical volumes of 993 boys with and without ADHD, and to subsamples of 653 adult men, 400 girls, and 447 women. Factor scores derived from the EFA were used to build networks.A community detection (CD) algorithm clustered participants into subgroups based on the networks.Results: Three factors (basal ganglia, limbic system, and thalamus) were found in boys and men with and without ADHD. The factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, though Community 3 was absent in healthy men. Significantly casecontrol differences of subcortical volumes were observed within communities in boys with increased effect sizes, but not in men. While we found no significant differences in ADHD symptom severity between communities in boys or men; affected men in Community 1 and 4 presented comorbidities more frequently than those in other communities. Conclusion:Our results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

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“…In the present study, we used custom Python code to access the Neurosynth database and generate reverse inference maps corresponding to terms of interest in ADHD, but otherwise all computational procedures were similar. We selected terms of interest based on the prior neurocognitive literature pertaining to ADHD (e.g., the excellent review by Mueller et al () and accessed the entire database of studies that is currently available in Neurosynth. Limitations remain, that are reviewed below (see Section 2.3).…”

Section: Methodsmentioning

confidence: 99%

“…We selected terms of interest based on the prior neurocognitive literature pertaining to ADHD (e.g., the excellent review by Mueller et al (2017) and accessed the entire database of studies that is currently available in Neurosynth. Limitations remain, that are reviewed below (see Section 2.3).…”

Section: Mapping Significant Effects To Neurocognitive Functional Mapsmentioning

confidence: 99%

“…Unfortunately, these categorical DSM subtypes have limited utility in predicting treatment response. Beyond the categorical symptom axes, impairment in 8 domains of neurocognitive function have been consistently associated with ADHD in targeted and meta‐analytic studies: cognitive flexibility, goal selection, response inhibition, response precision, selective attention, sustained attention, temporal information processing and working memory (Mueller, Hong, Shepard, & Moore, ). However, the categorical DSM nosology does not fully capture this multi‐system neurocognitive spectrum, and there is no clear way to map these 8 neurocognitive domains onto the categorical symptom axes of inattention and hyperactivity‐impulsivity.…”

Section: Introductionmentioning

confidence: 99%

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Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD

Lacy

Kodish

Rachakonda

et al. 2018

Human Brain Mapping

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From childhood to adolescence, strengthened coupling in frontal, striatal and parieto-temporal regions associated with cognitive control, and increased anticorrelation between task-positive and task-negative circuits, subserve the reshaping of behavior. ADHD is a common condition peaking in adolescence and regressing in adulthood, with a wide variety of cognitive control deficits. Alternate hypotheses of ADHD emphasize lagging circuitry refinement versus categorical differences in network function. However, quantifying the individual circuit contributions to behavioral findings, and relative roles of maturational versus categorical effects, is challenging in vivo or in meta-analyses using task-based paradigms within the same pipeline, given the multiplicity of neurobehavioral functions implicated. To address this, we analyzed 46 positively-correlated and anticorrelated circuits in a multivariate model in resting-state data from 504 age- and gender-matched youth, and created a novel in silico method to map individual quantified effects to reverse inference maps of 8 neurocognitive functions consistently implicated in ADHD, as well as dopamine and hyperactivity. We identified only age- and gender-related effects in intrinsic connectivity, and found that maturational refinement of circuits in youth with ADHD occupied 3-10x more brain locations than in typical development, with the footprint, effect size and contribution of individual circuits varying substantially. Our analysis supports the maturational hypothesis of ADHD, suggesting lagging connectivity reorganization within specific subnetworks of fronto-parietal control, ventral attention, cingulo-opercular, temporo-limbic and cerebellar sub-networks contribute across neurocognitive findings present in this complex condition. We present the first analysis of anti-correlated connectivity in ADHD and suggest new directions for exploring residual and non-responsive symptoms.

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Linking ADHD to the Neural Circuitry of Attention

Cited by 127 publications

References 161 publications

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD

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