Working memory-related functional brain patterns in never medicated children with ADHD

Abstract

Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental disorder characterized by 3 clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms are assumed to result from disturbances within brain systems supporting executive functions including working memory (WM), which refers to the ability to transiently store and flexibly manipulate task-relevant information. Ongoing or past medications, co-morbidity and differences in task performance are potential, independent confounds in assessing the integrity of cerebral patterns in ADHD. In the present study, we recorded WM-related cerebral activity during a memory updating N-back task using functional Magnetic Resonance Imaging (fMRI) in control children and never medicated, prepubescent children with ADHD but without comorbid symptoms. Despite similar updating performance than controls, children with ADHD exhibited decreased, below baseline WM-related activation levels in a widespread cortico-subcortical network encompassing bilateral occipital and inferior parietal areas, caudate nucleus, cerebellum and functionally connected brainstem nuclei. Distinctive functional connectivity patterns were also found in the ADHD in these regions, with a tighter coupling in the updating than in the control condition with a distributed WM-related cerebral network. Especially, cerebellum showed tighter coupling with activity in an area compatible with the brainstem red nucleus. These results in children with clinical core symptoms of ADHD but without comorbid affections and never treated with medication yield evidence for a core functional neuroanatomical network subtending WM-related processes in ADHD, which may participate to the pathophysiology and expression of clinical symptoms.

Figure 1. Working memory-related common and specific neural activity patterns in ADHD.

Left column: WM-related activation (N2> N0) in ADHD children. Middle column: WM-related activation (N2> N0) in Control children. Right column: higher WM activation (N2> N0) in Control than in ADHD children (interaction effect). All effects are displayed at p^unc <0.001, superimposed on the ICBM standardized anatomical template.

Figure 2. Percent BOLD signal changes from baseline levels in N2 and N0 conditions in Control and ADHD children.

OC: occipital cortex; IPC: inferior parietal cortex; VD: ventral dentate (cerebellum); CN: caudate nucleus; Crus I (cerebellum). Activated areas are displayed at p^unc <0.001, superimposed on the ICBM standardized anatomical template.

Figure 3. Functional connectivity patterns in ADHD. Brain areas in which activity is more tightly coupled with activity in the source area (A = left occipital, B = right cerebellum, C = inferior parietal, D = right caudate nucleus) in the working memory (N2) than the control (N0) condition, and more so in ADHD than Control children.

Functionally connected regions are displayed at p^unc <0.001, superimposed on the ICBM standardized anatomical template.