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.

Structure–function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders

“…Among the neurodevelopmental disorders with established links to cerebellar dysfunction, executive function deficits are most characteristic of ADHD. A recent study indicated that ADHD participants with impaired working memory show hypoactivation in the anterior cerebellum [56] and that bilateral regions of Crus I were hypoactive in ADHD participants during a working memory paradigm [57]. Gray matter reductions have been reported in multiple cerebellar regions in ADHD [35], including those that are associated with dorsal and ventral attention networks, and reduced functional connectivity has been found in cerebellar regions involved in fronto-parietal networks in children with ADHD [58].…”

Structure and Function of Large-Scale Brain Systems

“…In functional studies, these anomalies have been associated with inhibitory and working memory failures and attentional lapses (Q. Cao et al, 2013;Massat et al, 2012). Simply put, the auditory versus visual dichotomy initially proposed when neuropsychology was in its infancy is false, incomplete, and potentially diagnostically misleading.…”

A preliminary study of the effects of working memory training on brain function

“…We first compared ADHD to non-ADHD controls to localize any brain function deficits. Consistent with previous non-ADHD fMRI studies (Hempel et al, 2004; Jolles et al, 2010; Olesen et al, 2004), we predicted WM training would increase and possibly normalize ADHD WM task-related activation in some or most of these WM circuit regions, particularly left caudal superior frontal sulcus (SFS) and left inferior frontal sulcus (SFS) regions which most consistently show hypofunction in ADHD fMRI studies of short term WM storage (Fassbender et al, 2011; Hale et al, 2007; Prehn-Kristensen et al, 2011; Sheridan et al, 2007; Vance et al, 2007; Wolf et al, 2009) or WM updating (i.e., N-back tasks) (Bayerl et al, 2010; Cubillo et al, 2014; Ko et al, 2013; Kobel et al, 2009; Malisza et al, 2012; Massat et al, 2012; Passarotti et al, 2010; Valera et al, 2005). We also asked whether WM training preferentially altered ADHD brain function engaged during encoding, maintenance, or retrieval of information from WM and examined training effects on WM task difficulty.…”