Diffusion tensor imaging in attention deficit/hyperactivity disorder: A systematic review and meta-anlysis

Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 01/2012; 36(4):1093-106. DOI: 10.1016/j.neubiorev.2012.01.003
Source: PubMed


Diffusion tensor imaging (DTI) allows in vivo examination of the microstructural integrity of white matter brain tissue. A systematic review and quantitative meta-analysis using GingerALE were undertaken to compare current DTI findings in patients with ADHD and healthy controls to further unravel the neurobiological underpinnings of the disorder. Online databases were searched for DTI studies comparing white matter integrity between ADHD patients and healthy controls. Fifteen studies met inclusion criteria. Alterations in white matter integrity were found in widespread areas, most consistently so in the right anterior corona radiata, right forceps minor, bilateral internal capsule, and left cerebellum, areas previously implicated in the pathophysiology of the disorder. Current literature is critically discussed in terms of its important methodological limitations and challenges, and guidelines for future DTI research are provided. While more research is needed, DTI proves to be a promising technique, providing new prospects and challenges for future research into the pathophysiology of ADHD.

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    • "Studies examining voxel-based methods typically use fractional anisotropy (FA) as a metric of underlying microstructure , but some also further the interpretation using mean, axial and radial diffusivity (MD, AD and RD, respectively). Early studies of white matter connectivity in ADHD primarily used whole-brain, voxelwise analysis techniques, and reported widespread changes in microstructural organization in ADHD (See van Ewijk et al. 2012). A majority of the studies found differences in prefrontal white matter relevant to frontostriatal tracts. "
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    ABSTRACT: A growing body of work utilizing structural and functional brain imaging and neurocognitive measures of executive and attentional function indicates anomalous asymmetry in ADHD. This study examined the white-matter volume and diffusion properties of frontostriatal tracts, as a function of hemisphere, in ADHD and healthy controls. Forty-three young males (21 ADHD-Combined Type and 22 controls) aged 10-18 years underwent structural and diffusion weighted MRI. Tractography applying constrained spherical deconvolution (CSD) was used to construct frontostriatal tracts between each of caudate and putamen and each of dorsolateral prefrontal, ventrolateral prefrontal and orbitofrontal cortices (DLPFC, VLPFC and OFC) in each hemisphere, to examine both volumetric and diffusion microstructure properties. Young people with ADHD did not show the right hemisphere lateralization of volume in the Caudate-VLPFC and Caudate-DLPFC tracts that was evident in controls, however the ADHD group displayed a pronounced lateralization to the left for fractional anisotropy in the Putamen-VLPFC tracts. The degree of volume asymmetry did not correlate with symptom severity; however fractional anisotropy (FA) values that were more strongly lateralized to the left in the Putamen-VLPFC white matter were associated with greater symptom severity. ADHD was associated with anomalous hemispheric asymmetries in both tract volume and underlying white-matter microstructure in major fibre tracts of the frontostriatal system. Our observations of both weaker lateralization to the right in terms of tract volume and stronger lateralization to the left in terms of FA values for the ADHD group, suggests that previous inconsistencies in the literature may reflect the influence of such asymmetries.
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    • "However, we were concerned about limiting the number of regressors in our analyses to only those that were essential due to statistical problems that arise as the number of regressors increases (Breiman & Freedman, 1983). Because a recent meta-analysis of DTI studies in ADHD found the most consistent WM aberrations in this population in the anterior corona radiata, right forceps minor, bilateral internal capsule, and left cerebellum , rather than the uncinate fasciculus or stria terminalis/fornix (Van Ewijk et al. 2012), we concluded that this variable was not likely closely related to our hypotheses. It should also be noted that our study employed research assessments of conduct problems rather than clinical assessments of conduct disorder. "
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    ABSTRACT: Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings. We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10-17 years, of whom 26 exhibited conduct problems and varying levels of CU traits. Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits. These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.
    No preview · Article · Jun 2015 · Psychological Medicine
    • "The thalamocortical circuitry undergoes rapid morphological growth to adapt to the needs of numerous sensorimotor, cognitive, and attentional functions in early life (Gilmore et al., 2012; Holland et al., 2014; Qiu et al., 2013). Thalamocortical dysconnectivity, both structural and functional, has been implicated in children with autism spectrum disorder (Nair et al., 2013), attention deficit hyperactivity disorder (ADHD; Bush, 2011; Van Ewijka et al., 2012), and schizophrenia (Jones, 1997; Woodward et al., 2012). Abnormal thalamic development has also been found in preterm infants (Ball et al., 2012; Srinivasan et al., 2007), and survivors often suffer from cognitive and behavioral deficits and have an increased risk of developing autism and ADHD (D'Onofrio et al., 2013; Delobel-Ayoub et al., 2009). "
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    ABSTRACT: The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal, and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · NeuroImage
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