ebook_ADHD2019

The World Federation of ADHD Guide 25 healthy participants activate core network of brain regions involved in response inhibition, including a frontal-striatal and frontal-parietal network. 46 Most consis- tently, children and adolescents with ADHD show decreased activation in fron- tal, medial and parietal regions during inhibitions when compared with controls, 47 while for adults with ADHD hyperactivation has also been reported. Relative to comparison subjects, not only participants with ADHD but also their unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and com- parison subjects. 48 Furthermore, neural activation in inferior frontal nodes corre- lated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. These neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. 48 Together with alterations in brain activation during response inhibition, individuals with ADHD also had lower functional connectivity within the response inhibition network. The alterations in brain activations in the inhibition network in unaffected si- blings described above indicate that response inhibition may serve as a socalled endophenotype. Endophenotypes are biomarkers that share genetic loading with the disease liability, can be measured in all individuals (both affected and unaf- fected), and that are assumed to provide greater power to identify disease-related genes than clinical phenoptypes. 49 Since ADHD has strong genetic underpinnings and siblings on average share 50% of their genetic variation, unaffected siblings will on average have more ADHD risk genes than healthy controls. Thus, this suggests that part of the genetic loading for ADHD is mediated by alterations of response inhibition at the behavioural and neural level. WORKING MEMORY Working memory is considered to be the most central executive function. Three components of working memory are identified in Baddeley’s model. 50 The Central Executive (CE) acts as an attentional controller, coordinating tasks and activi- ties of its two sub-systems: the phonological loop (PL) and the visuospatial sket- chpad (VS), both storing modality-specific information. Deficient functioning of the separate systems translates into different performance deficits on cognitive tasks: limitations in storage capacity of the VS or PH subsystems is typically cha- racterised by a decline in task performance with increasing memory load or task difficulty. CE dysfunctioning generally translates into a general performance defi- cit, stable over different memory loads. Evidence suggests that deficits in working memory are one of the key cognitive impairments in ADHD, 51 with the strongest impairments reported for the spatial domain of working memory, as opposed to