An Integrated Analysis of Neural Network Correlates of Categorical and Dimensional Models of Attention-Deficit/Hyperactivity Disorder.
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, putatively induced by dissociable dysfunctional biobehavioral pathways. Here, we present a proof-of-concept study to parse ADHD-related heterogeneity in its underlying neurobiology by investigating functional connectivity across multiple brain networks to 1) disentangle categorical diagnosis-related effects from dimensional behavior-related effects and 2) functionally map these neural correlates to neurocognitive measures.


METHODS
We identified functional connectivity abnormalities related to ADHD across 14 networks within a large resting-state functional magnetic resonance imaging dataset (n = 409; age = 17.5 ± 3.3 years). We tested these abnormalities for their association with the categorical ADHD diagnosis and with dimensional inattention and hyperactivity/impulsivity scores using a novel modeling framework, creating orthogonalized models. Next, we evaluated the relationship of these findings with neurocognitive measures (working memory, response inhibition, reaction time variability, reward sensitivity).


RESULTS
Within the default mode network, we mainly observed categorical ADHD-related functional connectivity abnormalities, unrelated to neurocognitive measures. Clusters within the visual networks primarily related to dimensional scores of inattention and reaction time variability, while findings within the sensorimotor networks were mainly linked to hyperactivity/impulsivity and both reward sensitivity and working memory. Findings within the cerebellum network and salience network related to both categorical and dimensional ADHD measures and were linked to response inhibition and reaction time variability.


CONCLUSIONS
This proof-of-concept study identified ADHD-related neural correlates across multiple functional networks, showing distinct categorical and dimensional mechanisms and their links to neurocognitive functioning.
['Pruim|Raimon H R|RHR|', 'Beckmann|Christian F|CF|', 'Oldehinkel|Marianne|M|', 'Oosterlaan|Jaap|J|', 'Heslenfeld|Dirk|D|', 'Hartman|Catharina A|CA|', 'Hoekstra|Pieter J|PJ|', 'Faraone|Stephen V|SV|', 'Franke|Barbara|B|', 'Buitelaar|Jan K|JK|', 'Mennes|Maarten|M|']
D000293:Adolescent D001289:Attention Deficit Disorder with Hyperactivity D001921:Brain D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008959:Models, Neurological D009415:Nerve Net D009434:Neural Pathways
Neural networks Attention-deficit/hyperactivity disorder Connectivity Resting-state functional magnetic resonance imaging Categorical-dimensional analysis Neuropsychology rfMRI