Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition

Abstract

Background Understanding the neural processes tied to the adult outcome of childhood attention-deficit/hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are ‘fixed’, present even in remission. Using multimodal neuroimaging of inhibitory processes, we test these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD. Methods Adult participants (35 persistent ADHD; 47 remitted ADHD; 99 never affected) were scanned with fMRI (n=85), magnetoencephalography (n=33) or both (n=63) during a response inhibition task. Results In fMRI analyses, during inhibition, right caudate anomalies both reflected a childhood ADHD history and were present even among those who remitted. By contrast, differences related to adult outcome emerged in cortical (right inferior frontal and inferior parietal/precuneus) and cerebellar regions. Here, the persistent ADHD group showed under-activation, whereas the remitted ADHD group did not differ significantly from the never-affected group. MEG showed that the association between adult symptom severity and prefrontal neuronal activity was confined to the time window covering the act of inhibition (300–350 ms). Group differences in cerebellar and parietal neuronal activity occurred during the time window of performance monitoring processes (500–600 ms). Conclusions By combining fMRI and MEG we pinpoint the location and time window of neuronal activity that underpins the adult outcome of ADHD. We thus separate the cortico-cerebellar processes tied to clinical course of ADHD from the subcortical processes that are not.

A multicohort, longitudinal study of cerebellar development in attention deficit hyperactivity disorder

“…Meta-analysis of functional imaging studies show that ADHD is associated with hypoactivation of the left midline cerebellum during tasks that involve prediction of temporal events, along with the interconnected inferior parietal lobules (pertinent for attention to temporal information) and lateral inferior prefrontal cortex regions (temporal foresight and planning) (Hart, Radua, Mataix-Cols, & Rubia, 2012). Others highlight deficient response inhibition and impaired working memory as core deficits in ADHD, and both in turn have been linked to cerebellar hypoactivation (Rubia, Smith, Taylor, & Brammer, 2007; Szekely, Sudre, Sharp, Leibenluft, & Shaw, 2017; Wolf, 2009). Psychostimulant medication, the mainstay of treatment for ADHD, exerts a particularly potent effect on cerebellar activation, pointing to the structure as important in symptom mediation (Czerniak et al, 2013).…”

Early childhood Group-A streptococcal infections and basal ganglia antibodies in adult ADHD: A preliminary study

“…This rate was also in line with that found in adults affected by obsessive-compulsive disorder (19.8%, [35]), which represents one of the most known neuropsychiatric manifestation of post-streptococcal autoimmune basal ganglia disorders [36]. ADHD seems to be even more prevalent than obsessivecompulsive disorder in adult populations (2.8% vs. 1.2%, [4,37]) and, as mentioned above, the implication of structural and functional anomalies of basal ganglia in its pathophysiology has been well-recognized by neuroimaging studies [5,6,8,9]. However, the relationship between ADHD and post-infective basal ganglia disorders is little investigated, especially during adulthood, when the neurodevelopment is expected to be complete, thus neither infections nor autoimmunity process can longer affect its course.…”

“…Despite ADHD arises in childhood, it can persist in adulthood in about half of patients as a full-criteria disorder (45%-57%) [3,4], whereas a further 37% can show impairing symptoms or a subthreshold disorder at the 10 years after follow-up [3]. Neuroimaging and neurophysiological studies have consistently documented that improvement with age in core symptoms are accompanied by functional changes in cortical (right inferior frontal and inferior parietal/precuneus) and cerebellar regions [5,6], whereas basal ganglia anomalies (i.e., 3 right caudate) seem to be a peculiar lifetime feature of ADHD, regardless of adult remission [6,7].…”

Here/In This Issue and There/Abstract Thinking: Does This Answer Your Question?

“…5 Prior theories have been put forth arguing that those children who do “grow out of” ADHD do so because of normalization of their prefrontal cortical activity even while their subcortical activity remains altered. This study aimed to test this theory using a response inhibition task during functional magnetic resonance imaging and magnetoencephalography in a sample of adults with either persistent or remitted childhood ADHD compared to unaffected controls.…”