Detecting microstructural white matter abnormalities of frontal pathways in children with ADHD using advanced diffusion models

Wu, Weining; McAnulty, Gloria; Hamoda, Hesham M.; Sarill, Kiera; Karmacharya, Sarina; Gagoski, Borjan; Ning, Lipeng; Grant, P. Ellen; Shenton, Martha E.; Waber, Deborah P.; Makris, Nikolaos; Rathi, Yogesh

doi:10.1007/s11682-019-00108-5

Cited by 34 publications

(30 citation statements)

References 97 publications

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“…This reduced integrity of the CST may be associated with fine and gross motor difficulties, consistent hallmarks of ADHD (Mokobane, Pillay, & Meyer, 2019). Thus, our results replicate, in younger children, well-established findings regarding the group differences between youth diagnosed with ADHD and TD youth (e.g., see (Svatkova et al, 2016; Wu et al, 2020).…”

Section: Discussionsupporting

confidence: 90%

“…Notably, we did not find a difference in general FA across the whole brain, nor did we find a group difference in the cingulum. Differences in FA in cingulum have been found previously in studies of older children with ADHD (Svatkova et al, 2016; Wu et al, 2020), but not in all such studies (Ashtari et al, 2005; Davenport, Karatekin, White, & Lim, 2010), and not in children with CU behaviors (Pape et al, 2015) or CD (Finger et al, 2012; Haney-Caron et al, 2014). It is important to point out, though, that these studies showing differences have tended to be small sample studies (e.g., n < 30), increasing the possibility that such effects are spurious ((2015) is a notable exception).…”

Section: Discussionmentioning

confidence: 68%

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White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

Graziano

Garic

Dick

2020

Preprint

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Background: Callous-unemotional (CU) behaviors are important for identifying severe patterns of conduct problems (CP). One major fiber tract implicated in the development of CP is the uncinate fasciculus (UF), which connects amygdala and orbitofrontal cortex (OFC). The goals of the current study were to 1) explore differences in the white matter microstructure in the UF and other major fiber tracks (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], cingulum, and corticospinal tract [CST]) between young typically developing (TD) children and those with Attention-Deficit/Hyperactivity Disorder (ADHD), and 2) explore, within the ADHD group, whether individual differences in these white matter microstructures relate to co-occurring CP and CU behaviors, respectively. Methods: Participants included 198 young children (78% boys, Mage = 4.95 years; 80% Latinx; 49% TD). CU behaviors and CP were measured via a combination of teacher/parent ratings. Non-invasive diffusion-weighted imaging (DWI) was used to measure fractional anisotropy (FA), an indirect indicator of white matter properties. Results: Relative to TD children, children with ADHD had reduced FA on four out of the five fiber tracks we examined (except for cingulum). Within the ADHD group, no associations were found between CP and reduced white matter integrity across any of the fiber tracks examined. However, we found that even after accounting for CP and a host of covariates including whole brain FA, CU behaviors were independently related to reduced FA in bilateral UF and left IFOF. Conclusions: The bilateral UF and IFOF may be a biomarker of CU behaviors, even in very young children.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 68%

White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

Graziano

Garic

Dick

2020

Preprint

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“…Structural and functional imaging studies of ADHD have revealed differences spanning grey and white matter of all cortical lobes and many subcortical structures (4,5) suggestive of a distributed brain network disturbance, rather than a disorder with discrete regional abnormalities (6,7). Diffusion Tensor Imaging (DTI) of white matter connectivity in ADHD has also shown broad white matter changes within nearly all major tracts (8,9).…”

Section: Introductionmentioning

confidence: 99%

Tracking Inhibitory Control in Youth With ADHD: A Multi-Modal Neuroimaging Approach

et al. 2020

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Background: A decreased ability to inhibit a speeded motor response is a well-studied deficit in Attention Deficit Hyperactivity Disorder (ADHD), and has been proposed as an endophenotype. Inhibitory control has been assessed reliably with the Stop Signal Task (SST) and is associated with prior documented differences in regional brain function using f-MRI. Here, we advance on these findings by examining their structural connectivity and white matter integrity with the goal of identifying a network underlying a core cognitive deficit in ADHD. Methods: Healthy controls (N=16) and youth diagnosed with ADHD (N=60) were recruited through the Province of Ontario Neurodevelopmental Disorders Network (POND) and the Hospital for Sick Children. An f-MRI activation difference map was coregistered with each participant's white matter imaging data, representing the specific network nodes where ADHD youth diverged significantly from controls while performing the SST. Probabilistic tractography was applied from these nodes, and white matter integrity indices such as fractional anisotropy (FA) within the tracts of interest were contrasted between the groups and correlated with SST output measures, including the measure of inhibitory control, the stop signal reaction time (SSRT). Results: The tracts that connected the network nodes belonged primarily to the inferior fronto-occipital fasciculus (IFOF) and cingulum. ADHD subjects showed trend differences in FA compared to controls between right inferior frontal gyrus (IFG) and right superior temporal gyrus (P= 0.09), right IFG and right posterior cingulate (P= 0.01), right anterior cingulate to posterior cingulate (p= 0.08), and between left middle temporal gyrus (BA 39) and left posterior cingulate (P=0.02). A trend correlation was found between radial diffusivity within IFG to STG white matter (IFOF) and SSRT. Conclusions: We identified potential white matter tracts related to deficient inhibitory control, elucidating the brain mechanisms of an important cognitive deficit in ADHD. These

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“…The exact etiology of ADHD is still unknown, hypothesis based on experimental evidence reflect reduced brain function in association with reduced volume or functionality of gray and white matter in the brain, leading to deficits in cognitive processing, attention, motor planning, speed of processing responses, and other behavioral issues observed in ADHD (Cortese, 2012; Wu et al., 2019). More recently, the PFC, caudate, and cerebellum have emerged as the primary areas showing deficits in AD.…”

Section: Pathophysiologymentioning

confidence: 99%

Animal models of attention‐deficit hyperactivity disorder (ADHD)

Rahi

Kumar

2021

Intl J of Devlp Neuroscience

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Attention‐deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder characterized by three primary symptoms hyperactivity, attention deficit, and impulsiveness, observed in both children and adults. In childhood, this disorder is more common in boys than in girls, and at least 75% will continue to suffer from the disorder until adulthood. Individuals with ADHD generally have poor academic, occupational, and social functioning resulting from developmentally inappropriate levels of hyperactivity and impulsivity, as well as impaired ability to maintain attention on motivationally relevant tasks. Very few drugs available in clinical practice altogether abolish the symptoms of ADHD, therefore, to find new drugs and target it is essential to understand the neuropathological, neurochemical, and genetic alterations that lead to the progression of ADHD. With this contrast, an animal study is the best approach because animal models provide relatively fast invasive manipulation, rigorous hypothesis testing, as well as it provides a better angle to understand the pathological mechanisms involved in disease progression. Moreover, animal models, especially for ADHD, serve with good predictive validity would allow the assessment and development of new therapeutic interventions, with this aim, the present review collect the various animal models on a single platform so that the research can select an appropriate model to pursue his study.

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Detecting microstructural white matter abnormalities of frontal pathways in children with ADHD using advanced diffusion models

Cited by 34 publications

References 97 publications

White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

Tracking Inhibitory Control in Youth With ADHD: A Multi-Modal Neuroimaging Approach

Animal models of attention‐deficit hyperactivity disorder (ADHD)

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