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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    • "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.
    Psychological Medicine 06/2015; DOI:10.1017/S0033291715000987 · 5.94 Impact Factor
    • "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.
    NeuroImage 03/2015; 116. DOI:10.1016/j.neuroimage.2015.03.039 · 6.36 Impact Factor
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    • "Moreover, tractography algorithms can use diffusion tensor information to estimate the location and direction of fiber tracts. DTI has been used to characterize abnormal white matter diffusion properties in a range of diseases, including psychiatric disorders involving psychosis and disturbances in mood and attention [4,5,8,9]. "
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    ABSTRACT: Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs.
    Biology of Mood and Anxiety Disorders 09/2014; 4(1):8. DOI:10.1186/2045-5380-4-8
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