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Neurocognitive Pathways in Attention-Deficit/Hyperactivity Disorder and White Matter Microstructure.

ABSTRACT: BACKGROUND:This study sought to identify attention-deficit/hyperactivity disorder (ADHD) abnormalities in relationships between brain white matter structure and individual differences in several types of impulsive behavior. METHODS:Adolescents, n = 67 with ADHD combined subtype and n = 68 without ADHD, were given neuropsychological tests and underwent diffusion tensor imaging scans. Principal component analysis reduced test scores into factors representing different types of impulsive behavior. Tract-based spatial statistics quantified white matter integrity in relationship to components of impulsive behavior. ADHD versus non-ADHD differences in the strength and nature of linear relationships between regional white matter and three impulsivity components were examined using multiple regression. RESULTS:Principal component analysis found three separate impulsivity-related factors that were interpreted as motor response inhibition, impulsive choice, and delay aversion. Relationships between regional fractional anisotropy and response inhibition or impulsive choice did not differ between ADHD and non-ADHD groups. There was a significant interaction between diagnostic group and delay aversion test performance relationships with regional fractional anisotropy. For youths without ADHD, greater anisotropy in numerous tracts predicted better delay aversion test performance. In contrast, anisotropy in regions including the corpus callosum, corona radiata, internal capsule, and corticospinal tracts had either a negative or no relationship with delay aversion test performance in ADHD. CONCLUSIONS:The results provide additional support that different proposed etiological pathways to ADHD have discretely different neurobiological features. Large disorganization of white matter microstructure appears to contribute to reward-based ADHD pathways rather than motor inhibition.

SUBMITTER: Bessette KL

PROVIDER: S-EPMC6549508 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Neurocognitive Pathways in Attention-Deficit/Hyperactivity Disorder and White Matter Microstructure.

Bessette Katie L KL Stevens Michael C MC

Biological psychiatry. Cognitive neuroscience and neuroimaging 20180929 3

<h4>Background</h4>This study sought to identify attention-deficit/hyperactivity disorder (ADHD) abnormalities in relationships between brain white matter structure and individual differences in several types of impulsive behavior.<h4>Methods</h4>Adolescents, n = 67 with ADHD combined subtype and n = 68 without ADHD, were given neuropsychological tests and underwent diffusion tensor imaging scans. Principal component analysis reduced test scores into factors representing different types of impul ...[more]

PMID: 30478002

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Project description:BackgroundAttention-deficit/hyperactive disorder (ADHD) has substantial heterogeneity in clinical presentation. A potentially important clue may be variation in brain microstructure. Using fractional anisotropy (FA), previous studies have produced equivocal results in relation to ADHD. This may be due to insufficient consideration of possible sex differences and ADHD's multi-componential nature.MethodsUsing whole-brain analyses, we investigated the association between FA and both ADHD diagnosis and ADHD symptom domains in a well-characterized, ADHD (n = 234; 32% female youth) and non-ADHD (n = 177; 52% female youth), case-control cohort (ages 7-12). Sex-specific effects were tested.ResultsNo ADHD group differences were found using categorical assessment of ADHD without consideration of moderators. However, dimensional analyses found total symptoms were associated with higher FA in the superior corona radiata. Further, inattention symptoms were associated with higher FA in the corpus callosum and ansa lenticularis, and lower FA in the superior longitudinal fasciculus, after control for overlap with hyperactivity-impulsivity. Hyperactivity-impulsivity symptoms were associated with higher FA in the superior longitudinal fasciculus, and lower FA in the superior cerebellar peduncles, after control for overlap with inattention. Meanwhile, both categorical and dimensional analyses revealed ADHD-by-sex interactions (voxel-wise p < 0.01). Girls with ADHD had higher FA, but boys with ADHD had lower FA (or no effect), compared to their same-sex peers, in the bilateral anterior corona radiata. Further, higher ADHD symptom severity was associated with higher FA in girls, but lower FA in boys, in the anterior and posterior corona radiata and cerebral peduncles.ConclusionsADHD symptom domains appear to be differentially related to white matter microstructure, highlighting the multi-componential nature of the disorder. Further, sex differences will be crucial to consider in future studies characterizing ADHD-related differences in white matter microstructure.

Project description:Attention-deficit/hyperactivity disorder has been identified to involve the impairment of large-scale functional networks within grey matter, and recent studies have suggested that white matter, which also encodes neural activity, can manifest intrinsic functional organization similar to that of grey matter. However, the alterations in white matter functional networks in attention-deficit/hyperactivity disorder remain unknown. We recruited a total of 99 children, including 66 drug-naive patients and 33 typically developing controls aged from 6 to 14, to characterize the alterations in functional networks within white matter in drug-naive children with attention-deficit/hyperactivity disorder. Using clustering analysis, resting-state functional MRI data in the white matter were parsed into different networks. Intrinsic activity within each network and connectivity between networks and the associations between network activity strength and clinical symptoms were assessed. We identified eight distinct white matter functional networks: the default mode network, the somatomotor network, the dorsal attention network, the ventral attention network, the visual network, the deep frontoparietal network, the deep frontal network and the inferior corticospinal-posterior cerebellum network. The default mode, somatomotor, dorsal attention and ventral attention networks showed lower spontaneous neural activity in patients. In particular, the default mode network and the somatomotor network largely showed higher connectivity with other networks, which correlated with more severe hyperactive behaviour, while the dorsal and ventral attention networks mainly had lower connectivity with other networks, which correlated with poor attention performance. In conclusion, there are two distinct patterns of white matter functional networks in children with attention-deficit/hyperactivity disorder, with one being the hyperactivity-related hot networks including default mode network and somatomotor network and the other being inattention-related cold networks including dorsal attention and ventral attention network. These results extended upon our understanding of brain functional networks in attention-deficit/hyperactivity disorder from the perspective of white matter dysfunction.

Project description:ImportanceClinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date.ObjectiveTo examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches.Design, setting, and participantsThis investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015.Main outcomes and measuresThe primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA).ResultsThis cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software.Conclusions and relevanceDimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms.

Project description:BackgroundMagnetic resonance imaging (MRI) is able to provide detailed insights into the structural organization of the brain, e.g., by means of mapping brain anatomy and white matter microstructure. Understanding interrelations between MRI modalities, rather than mapping modalities in isolation, will contribute to unraveling the complex neural mechanisms associated with neuropsychiatric disorders as deficits detected across modalities suggest common underlying mechanisms. Here, we conduct a multimodal analysis of structural MRI modalities in the context of attention-deficit/hyperactivity disorder (ADHD).MethodsGray matter volume, cortical thickness, surface areal expansion estimates, and white matter diffusion indices of 129 participants with ADHD and 204 participants without ADHD were entered into a linked independent component analysis. This data-driven analysis decomposes the data into multimodal independent components reflecting common inter-subject variation across imaging modalities.ResultsADHD severity was related to two multimodal components. The first component revealed smaller prefrontal volumes in participants with more symptoms, co-occurring with abnormal white matter indices in prefrontal cortex. The second component demonstrated decreased orbitofrontal volume as well as abnormalities in insula, occipital, and somato-sensory areas in participants with more ADHD symptoms.ConclusionsOur results replicate and extend previous unimodal structural MRI findings by demonstrating that prefrontal, parietal, and occipital areas, as well as fronto-striatal and fronto-limbic systems are implicated in ADHD. By including multiple modalities, sensitivity for between-participant effects is increased, as shared variance across modalities is modeled. The convergence of modality-specific findings in our results suggests that different aspects of brain structure share underlying pathophysiology and brings us closer to a biological characterization of ADHD.

Dataset Information

Neurocognitive Pathways in Attention-Deficit/Hyperactivity Disorder and White Matter Microstructure.

Publications

Neurocognitive Pathways in Attention-Deficit/Hyperactivity Disorder and White Matter Microstructure.

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