Connectomic Disturbances in Attention-Deficit/Hyperactivity Disorder: A Whole-Brain Tractography Analysis

doi:10.1016/j.biopsych.2013.12.013

Biological Psychiatry

Volume 76, Issue 8, 15 October 2014, Pages 656-663

https://doi.org/10.1016/j.biopsych.2013.12.013 Get rights and content

Background

Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD.

Methods

Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD.

Results

A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores.

Conclusions

Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD.

Section snippets

Participants

Children and adolescents with ADHD were recruited from the Seoul National University Hospital in Korea. A total of 81 ADHD participants and 27 healthy control subjects were initially recruited. Attention-deficit/hyperactivity disorder patients with an IQ below 70; a past or an ongoing history of either tic disorder, obsessive-compulsive disorder, language disorder, learning disorder, convulsive disorder, pervasive developmental disorder, schizophrenia, bipolar disorder, or brain damage; a past

Participant Characteristics

No significant difference was found in age and handedness between ADHD and control groups (Table 1). A significant male predominance was found in ADHD participants, reflecting the gender ratio of this population (1). IQ was higher in healthy control subjects (26), and no significant difference was found between the two groups in social and obstetric variables, except higher paternal education level in healthy control subjects. Sixty-one ADHD patients (85.9%) were drug-naïve and 10 ADHD patients

Discussion

Evidence of altered white matter connectivity was found in children and adolescents with ADHD. The aberrant network differentiating ADHD individuals from healthy control subjects involved prefrontal and striatal pathology. Interestingly, ventral frontal regions were implicated, such as orbitofrontal cortex, pars triangularis, and gyrus rectus. Basal ganglia regions included the putamen and globus pallidus but not caudate nucleus. The network identified involved prefrontal and striatal

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View all citing articles on Scopus

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Archival ReportConnectomic Disturbances in Attention-Deficit/Hyperactivity Disorder: A Whole-Brain Tractography Analysis

Background

Methods

Results

Conclusions

Section snippets

Participants

Participant Characteristics

Discussion

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Neurosci Biobehav Rev

Biol Psychiatry

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Neuroimage

Neuroimage

Psychiatry Res

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Trends Cogn Sci

J Am Acad Child Adolesc Psychiatry

Clin Psychol Rev

Trends Cogn Sci

Electroencephalogr Clin Neurophysiol

Neuroimage

Neuroimage

Neuroimage

The worldwide prevalence of ADHD: A systematic review and metaregression analysis

Am J Psychiatry

Attention-deficit/hyperactivity disorder and attention networks

Neuropsychopharmacology

Towards conceptualizing a neural systems-based anatomy of attention-deficit/hyperactivity disorder

Dev Neurosci

Gray matter volume abnormalities in ADHD: Voxel-based meta-analysis exploring the effects of age and stimulant medication

Am J Psychiatry

The reward circuit: Linking primate anatomy and human imaging

Neuropsychopharmacology

MR diffusion tensor imaging: A window into white matter integrity of the working brain

Neuropsychol Rev

Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD

Am J Psychiatry

White matter tract integrity of frontostriatal circuit in attention deficit hyperactivity disorder: Association with attention performance and symptoms

Hum Brain Mapp

Discovering the Human Connectome

Archival Report
Connectomic Disturbances in Attention-Deficit/Hyperactivity Disorder: A Whole-Brain Tractography Analysis