[R01] Neurobehavioral consequences of Mild Traumatic Brain Injury and addiction risk: a cotwin-control study
Ente: National Institute on Drug Abuse
Scadenza: 2028-07-31
Importo max: 698.328 EUR
Paese: US
Descrizione
Project Summary/Abstract
The overall goal of the proposed study is to identify long-term neurobehavioral consequences of childhood mild
traumatic brain injury (mTBI) for the developing brain and examine their contribution to addiction risk using a
rigorous cotwin-control design, longitudinal follow-up, and multimodal and innovative neuroimaging tools and
neurobehavioral assessments. mTBI sustained during childhood or adolescence, periods of continuing brain
development and reorganization, is a major public health problem due to its high prevalence and long-lasting
neurobehavioral consequences associated with increased risk for addictive behaviors. However, progress in
understanding long-term sequelae of mTBI and their role in addiction is hindered by a number of significant
methodological challenges: a) case-control studies are correlative and do not allow to distinguish consequences
of TBI from pre-existing neurocognitive deficits potentially increasing the risk for TBI; b) matching cases and
controls is very problematic due to substantial (and largely heritable) individual variability in brain structure and
function and heterogeneity of brain damage; c) single neuroimaging modalities provide only a limited insight into
the consequences of mTBI; d) in cross-sectional studies, the effects of mTBI may be confounded with the effects
of substance use. The proposed study will address these critical barriers to progress using a combination of
rigorous and innovative approaches: (i) the co-twin control design that will provide the best-possible controls for
mTBI cases - their monozygotic co-twins without TBI history, (ii) multimodal neuroimaging assessments
leveraging high spatial resolution of MRI and high temporal resolution of brain electrophysiology, and (iii) a
longitudinal follow-up assessment of changes in substance use behaviors (onset, regular use, substance use
disorder symptoms). Assessment will include structural, functional, and diffusion MRI, quantitative Gradient
Recalled Echo (qGRE) MRI, a novel neuroimaging technique sensitive to cortical cellular microstructure, brain
neurophysiology including resting-state EEG, and event-related brain potentials (ERP), methods that are
sensitive to abnormal timing and synchrony of neuronal dynamics. The following Specific Aims will be pursued:
Aim 1: To identify long-term consequences of mTBI in early adolescence and distinguish them from pre-existing
factors potentially associated with risk for mTBI using a cotwin control design. We hypothesize that, in mTBI-
discordant monozygotic pairs, twins with lifetime history of mTBI will show alterations in brain structure and
function and deficits in neuropsychological performance compared with their cotwins without mTBI history; Aim
2: To determine, both cross-sectionally and prospectively, whether mTBI is associated with elevated risk for
addictive behaviors. A better understanding of the mechanisms by which long-lasting neurobehavioral
consequences of ch
Istituzione: WASHINGTON UNIVERSITY
PI: Andrey P. Anokhin
Progetto: 5R01DA058114-04
Settori: National Institute on Drug Abuse
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