SCCAP/APA Convention/2018/The Neuroscience of ADHD from Childhood to Early Adulthood: Insights from neuroimaging

This symposium, titled, The neuroscience of ADHD from childhood to early adulthood: Insights from neuroimaging, highlights the results of three recent investigations that use complementary neuroimaging approaches (fNIRS, fMRI+DTI, combined MEG/fMRI) to explicate the neuro-underpinnings of three potential contributors to the heterogeneity of ADHD􀂲viz., working memory (WM) deficits, striatal connectivity, and symptom persistence into adulthood.

The initial study introduces functional Near InfraRed Spectroscopy (fNIRS) as a neuroimaging technique to localize/quantify neural activation patterns associated with WM performance deficiencies in children with ADHD relative to neurotypical (NC) children. It also examines whether between-group differences reflect underdeveloped regional activity and/or compensatory processes in ADHD. The second study illuminates consistent alterations in caudate activity and broader striatalcortico and striatal-limbic structural connectivity using both fMRI and probabilistic tractography in adolescents and young adults with ADHD, combined presentation versus typically developing individuals. Striatal functional and structural connectivity alterations in ADHD appear related to greater cognitive load and ADHD symptoms. The third study uses combined fMRI and magnetoencephalography (MEG) to prospectively investigate a large cohort of children with and without ADHD into adulthood. The study addresses why some children grow out of ADHD and exhibit variable degrees of remission from the disorder, whereas others have symptoms that persist into adulthood. It also examines whether remission occurs due to compensatory processes underpinned by neural re-organization as opposed to whether remission reflects the 􀂵normalization􀂶􀀃of childhood transient anomalies in brain structure and function.

Mark Rapport, PhD, "Working Memory Deficits in Children with ADHD: Insights from Functional Neuroimaging Spectroscopy"
Attention-deficit/hyperactivity disorder (ADHD) is an early onset neurodevelopmental disorder that affects an estimated 5.4 million children in the United States at an annual cost of approximately $42.5 billion based on cost of illness (COI) estimates. A majority of these costs are associated with educational accommodations to address the significant difficulties children with ADHD experience at school and elevated risk for academic failure in core foundational areas (e.g., reading, math). Working memory (WM)􀂲a critical set of cognitive processes needed for core foundational learning􀂲is significantly underdeveloped in a majority of children with ADHD and mediates the relations between diagnostic status, reading, math, and core clinical symptoms. WM is comprised of an upper level central executive (CE) supervisory attentional controller which governs/processes information held temporarily in anatomically distinct phonological and visuospatial short-term memory (STM) stores. Although there is a high degree of consensus that CE deficits are more pronounced than STM deficits in ADHD, it is unknown currently whether these differences reflect underlying differences in neuro activation patterns. This project introduces functional Near InfraRed Spectroscopy (fNIRS) as a cost efficient, movement tolerant, neuroimaging technique to localize/quantify neural activation patterns based on blood oxygen level dependent (BOLD) levels associated with WM task-related performance deficiencies in children with ADHD (n=15) relative to neurotypical (NC) children (n=15). Our results revealed significant between-group differences in cognitive performance and corresponding neural activation patterns associated with upper level WM CE tasks relative to STM tasks, and support current conceptual views of ADHD as a neurodevelopmental disorder rather than a behavioral-disruptive disorder of childhood. We discuss the implication of these results for informing the design of advanced intra-individual cognitive training platforms that target and strengthen identified WM functional deficits that underlie foundation learning and academic performance consistent with the NIMH Research Domain criteria (RDoC) initiative.

Julie B Schweitzer, PhD, "Assessing the contributions of the striatum toward functioning in ADHD using multimodal imaging"
Our core hypothesis is that ADHD Combined Presentation (i.e., hyperactive/impulsive and inattentive symptoms) reflects an imbalance in reward-driven and cognitive/goal-driven behavioral and neurocognitive functioning. We explore this hypothesis using a combination of multi-modal imaging (i.e., fMRI and DTI) techniques and symptom measures in adolescents and young adults with ADHD. We used fMRI and a working memory paradigm to explore the functional neural alterations in the cognitive/goal-driven system in 50 participants with combined presentation of ADHD and 89 typically developing adolescents and young adults. We found the caudate implicated when the working memory task required more effort, including higher load (i.e., remember 4 versus 3 objects) and manipulation of information versus maintenance of objects with differential caudate activity in the ADHD than typical group in the more challenging conditions (p < 0.005, corrected). Effects of operation (manipulation versus maintenance) were also noted in the right cerebellum. We used probabilistic tractography of the mesostriatal tracts to compare structural brain differences between mesolimbic and mesocortical dopaminergic pathways in these same participants (ADHD n = 71; typical n = 79). The striatum was segmented based on cortical target regions (i.e., limbic, executive and sensorimotor). Initial results found parent inattentive ratings negatively associated with executive/mesocortical tract strength; whereas mesolimbic tract strength was not associated with inattentive ratings. Impulsivity ratings were negatively associated with executive/mesocortical tract strength. Research on the role of the striatum and its connections to cortical and subcortical structures in persons with ADHD may be particularly illuminating in identifying subgroups of persons with ADHD who experience different vulnerabilities for co-morbid psychiatric disorders and response to treatment.

Philip Shaw, MD, PhD, "Adult remission in attention deficit hyperactivity disorder: Insights from multimodal imaging"
Why do some children grow out of ADHD, showing variable degrees of remission from the disorder, whereas others have symptoms that persist into adulthood? Is remission due to the emergence of compensatory processes underpinned by neural re-organization? Or is remission due to the 􀂵normalization􀂶􀀃of early, childhood transient anomalies in brain structure and function? To address this question, we followed prospectively a cohort of 92 children with and 104 without ADHD into adulthood (mean age at study entry 10.2 (SD3) years; adult endpoint 24 (SD4) years). By adulthood, 37 (40%) showed persistent ADHD, the remainder no longer met criteria for ADHD. White matter tract (diffusion tensor imaging) and multimodal functional imaging (fMRI and magnetoencephalography-MEG) were acquired at the adult endpoint (on a 3 Tesla G.E. scanner). We find that young adults whose ADHD has persisted from childhood show atypical neural features, whereas remitters do not differ from those who were never affected. This pattern held for white matter microstructure and intrinsic functional connectivity (defined through task free fMRI and MEG). Further, during a probe of motor inhibition, a core deficit in the disorder, we find remitters show typical hemodynamic and electrophysiological activity at both cortical and cerebellar levels. Combined, the findings suggest that remission is aligned to processes that may partly 􀂵normalize􀂶􀀃 early anomalies in brain structure and function rather than the emergence of compensatory strategies and neural reorganization.