Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents

Abstract

BACKGROUND Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. Herein, we investigate the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability—an index of lapses in attention. We also test for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression. METHODS Psychopathology and imaging data were available for 1,538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment (DAWBA) and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptomatology were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole brain voxel-wise regressions with gray matter volume (GMV) were calculated. RESULTS Parent ratings of ADHD symptoms (DAWBA and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with GMV in an overlapping region of the ventromedial prefrontal cortex (vmPFC). Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology. CONCLUSIONS This is the first study to reveal relations between vmPFC structure and multi-informant measures of ADHD symptomatology in a large population-based sample of adolescents. Our results indicate that vmPFC structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.

Anterior insula hyperactivation in ADHD when faced with distracting negative stimuli

“…The current findings of hyperactivation of the insula during negative stimuli add to the evidence for an insula dysfunction in ADHD, but suggest that the sign of the activation deficit is contextdependent: the insula appears to be underactive in ADHD in the context of cognitive tasks that are typically more boring to these adolescents and hence subjectively "undersalient" (Cubillo et al, 2011;Rubia et al, 2007Rubia et al, , 2009bRubia et al, , 2011a, while during negative emotions, which are strongly salient for ADHD, the insula seems to be hyperactive. Current findings fit to a recent ADHD sMRI study with a large populationbased sample (Albaugh et al, 2017) Speculatively, only the acute pharmaceutical effect of MPH may lead to a "normalized" brain activation for emotional attention, that is, no differences from TD as shown for the group with long-term medication without MPH pause in Posner et al (2011aPosner et al ( , 2011b. However, contrasting findings exist for a "cool" attentional reorienting task showing "normalized" brain activation for the insula and striatum after one year of MPH and one week break before the study (Konrad, Neufang, Fink, & Herpertz-Dahlmann, 2007).…”

“…The current findings of hyperactivation of the insula during negative stimuli add to the evidence for an insula dysfunction in ADHD, but suggest that the sign of the activation deficit is context‐dependent: the insula appears to be underactive in ADHD in the context of cognitive tasks that are typically more boring to these adolescents and hence subjectively “undersalient” (Cubillo et al, ; Rubia et al, ), while during negative emotions, which are strongly salient for ADHD, the insula seems to be hyperactive. Current findings fit to a recent ADHD sMRI study with a large population‐based sample (Albaugh et al, ) which found that dimensional, multi‐informant measures of ADHD symptomatology in adolescents and RT variability were negatively associated with ventromedial PFC volume, an area that regulates amygdala activity (Motzkin, Philippi, Wolf, Baskaya, & Koenigs, ).…”

Neural circuitry underlying sustained attention in healthy adolescents and in ADHD symptomatology

“…NeuroImage 169 (2018) 395-406 (Langner and Eickhoff, 2013;Corbetta and Shulman, 2002) and these findings lend support to previous structural findings, which linked prefrontal anomalies to increased IRV (Albaugh et al, 2017). The cerebellum is thought to have a critical role in sustained attention (Habas et al, 2009;Stoodley, 2012;Buckner, 2013).…”

“…Neurological and psychopathological research is increasingly revealing a dimensionality aspect to developmental disorders such as ADHD (Hudziak et al, 2007) and conceptualizing attention-related traits as existing along a continuum shifts the focus from diagnostic groups towards diagnostic dimensions (O'Halloran et al, 2017). For example, reduced ventromedial prefrontal gray matter volume was associated with increased IRV in adolescents with elevated ADHD symptoms (Albaugh et al, 2017). Therefore, it is plausible that the (disrupted) functional connectivity patterns related to IRV in ADHD may be apparent among those with subclinical attention difficulties.…”

Dimensional neuroimaging: (Internet) Gaming Disorder symptoms according to the WHO and APA frameworks associate with lower striatal volume

“…Initial studies in the general population reported associations between the extent of gaming or the level of "internet addiction"-associated symptoms and gray matter volume in reward processing regions, including the striatum (Kuhn et al, 2011;Montag et al, 2017;Zhou et al, 2019), suggesting that progressive volumetric changes in this region may accompany the transition into IGD. With the advent of the Research Domain Criteria approach dimensional imaging approaches have been increasingly employed in normal and pathological populations to map associations between pathology-relevant symptom dimensions and progressive dysregulations in the underlying brain systems (Albaugh et al, 2017;Li et al, 2019).…”