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White matter alterations at 33-year follow-up in adults with childhood attention-deficit/hyperactivity disorder.

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is increasingly conceived as reflecting altered functional and structural brain connectivity. The latter can be addressed with diffusion tensor imaging (DTI). We examined fractional anisotropy (FA), a DTI index related to white matter structural properties, in adult male subjects diagnosed with ADHD in childhood (probands) and matched control subjects without childhood ADHD. Additionally, we contrasted FA among probands with and without current ADHD in adulthood and control subjects.Participants were from an original cohort of 207 boys and 178 male control subjects. At 33-year follow-up, analyzable DTI scans were obtained in 51 probands (41.3 ± 2.8 yrs) and 66 control subjects (41.2 ± 3.1 yrs). Voxel-based FA was computed with tract-based spatial statistics, controlling for multiple comparisons.Probands with childhood ADHD exhibited significantly lower FA than control subjects without childhood ADHD in the right superior and posterior corona radiata, right superior longitudinal fasciculus, and in a left cluster including the posterior thalamic radiation, the retrolenticular part of the internal capsule, and the sagittal stratum (p<.05, corrected). Fractional anisotropy was significantly decreased relative to control subjects in several tracts in both probands with current and remitted ADHD, who did not differ significantly from each other. Fractional anisotropy was not significantly increased in probands in any region.Decreased FA in adults with childhood ADHD regardless of current ADHD might be an enduring trait of ADHD. White matter tracts with decreased FA connect regions involved in high-level as well as sensorimotor functions, suggesting that both types of processes are involved in the pathophysiology of ADHD.

SUBMITTER: Cortese S

PROVIDER: S-EPMC3720804 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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White matter alterations at 33-year follow-up in adults with childhood attention-deficit/hyperactivity disorder.

Cortese Samuele S Imperati Davide D Zhou Juan J Proal Erika E Klein Rachel G RG Mannuzza Salvatore S Ramos-Olazagasti Maria A MA Milham Michael P MP Kelly Clare C Castellanos F Xavier FX

Biological psychiatry 20130406 8

<h4>Background</h4>Attention-deficit/hyperactivity disorder (ADHD) is increasingly conceived as reflecting altered functional and structural brain connectivity. The latter can be addressed with diffusion tensor imaging (DTI). We examined fractional anisotropy (FA), a DTI index related to white matter structural properties, in adult male subjects diagnosed with ADHD in childhood (probands) and matched control subjects without childhood ADHD. Additionally, we contrasted FA among probands with and ...[more]

PMID: 23566821

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Project description:Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood.To test whether adults with combined-type childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis, including persistent vs remitting ADHD.Cross-sectional analysis embedded in a 33-year prospective follow-up at a mean age of 41.2 years.Research outpatient center.We recruited probands with ADHD from a cohort of 207 white boys aged 6 to 12 years. Male comparison participants (n = 178) were free of ADHD in childhood. We obtained magnetic resonance images in 59 probands and 80 comparison participants (28.5% and 44.9% of the original samples, respectively).Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses.The cortex was significantly thinner in ADHD probands than in comparison participants in the dorsal attentional network and limbic areas (false discovery rate < 0.05, corrected). In addition, gray matter was significantly decreased in probands in the right caudate, right thalamus, and bilateral cerebellar hemispheres. Probands with persistent ADHD (n = 17) did not differ significantly from those with remitting ADHD (n = 26) (false discovery rate < 0.05). At uncorrected P < .05, individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex, insula, parahippocampus, and prefrontal regions.Anatomic gray matter reductions are observable in adults with childhood ADHD, regardless of the current diagnosis. The most affected regions underpin top-down control of attention and regulation of emotion and motivation. Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal, cerebellar, and thalamic circuitry.

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.

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.

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White matter alterations at 33-year follow-up in adults with childhood attention-deficit/hyperactivity disorder.

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White matter alterations at 33-year follow-up in adults with childhood attention-deficit/hyperactivity disorder.

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