Normative dopaminergic function and activation of cognitive control: neuroimaging studies across the lifespan
Aims:
Dopamine (DA) plays a prominent role in brain health across the human life span in several ways; ADHD (attention-deficit/hyperactivity disorder) is a common neurodevelopmental disorder for which dopamine stimulants offer effective symptom management; cognitive impairments due to DA losses are commonly associated with typical aging. Yet there are fundamental gaps in our knowledge in terms of the precise, normative age-related DA trajectories across the lifespan, and of the neurocognitive mechanisms by which DA influences mental processing.
The overarching goal of the present project is to bridge these gaps by using safe ultra-low-dose PET (positron emission tomography) for in vivo growth-charting of the DA system, while integrating information from multimodal structural and functional imaging, and critically, from intricate computational cognitive modeling to clarify the neurocognitive implications of DA. Ultimately the present research aims to shed light on the capacity versus motivational implications of DA at these extreme age groups, to empower the future of DA-related brain health.
Research materials and methods:
The research is conducted on healthy young (approx. 10 – 19 years) and elderly participants (> 65 years) using the imaging facilities at Turku PET Centre (TPC). The first phase of the project focuses on establishing ethically sustainable ultra-low-dose PET for pediatric imaging. An effective dose of 0.25 micro-Sievert (mSv) – similar to an annual dose from within body carbon-14 isotopes – is considered ethically sustainable in relation to the value of knowledge that can only be obtained using PET. In this pursue, total-body PET at TPC represents a unique advantage in terms of dramatic improvements in sensitivity, permitting up to 80% radioactive dose reductions. The ALARA (as low as reasonably achievable) principle, however, warrants further efforts to reduce the radioactive dose. For this purpose, computational techniques for image enhancement in ultra-low-dose PET, including machine-learning, are implemented and validated using previously collected data at TPC. During this phase pilot data are collected (~5+5 young and elderly) and disseminated as proof-of-concept.
The second phase of the project, paralleled with the proof-of-concept, involves application for additional research funding for large-scale data collection. The ambition is to include approximately fifty participants in both age groups to ensure solid statistical fundament. Throughout the project an integrative pipeline across imaging phenotypes, cognitive outcomes and exogenous parameters such as health and affective components, using cutting-edge analytic approaches is employed