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Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

ABSTRACT: Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7-12 years old) with (n = 40) and without (n = 30) a formal diagnosis of ADHD. A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature.

SUBMITTER: Nomi JS

PROVIDER: S-EPMC5857584 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

Nomi Jason S JS Schettini Elana E Voorhies Willa W Bolt Taylor S TS Heller Aaron S AS Uddin Lucina Q LQ

Frontiers in human neuroscience 20180312

Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between res ...[more]

PMID: 29593515

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Project description:Background: The basic functional organization of the resting brain, assessed as resting-state functional connectivity (rsFC), can be affected by previous stress experience and it represents the basis on which subsequent stress experience develops. Notably, the rsFC between the amygdala and the cortical regions associated with emotion regulation and anxiety are affected during stress. The multicomponent drug Neurexan® (Nx4) has previously demonstrated a reduction in amygdala activation in an emotional face matching task and it ameliorated stress-related symptoms. We, thus, investigated the effect of Nx4 on rsFC of the amygdala before stress induction compared with baseline in mildly to moderately stressed participants. Methods: In a randomized, placebo-controlled, double-blind, crossover trial 39 participants received a single dose of placebo or Nx4. Resting-state functional magnetic resonance imaging scans were performed pre-dose and 40 to 60 min post-dose, before any stress induction. First, highly connected functional hubs were identified by global functional connectivity density (gFCD) analysis. Second, by using a seed-based approach, rsFC maps of the left centromedial amygdala (CeMA) were created. The effect of Nx4 on both was evaluated. Results: The medial prefrontal cortex was identified as a relevant functional hub affected by Nx4 in an explorative whole brain gFCD analysis. Using the seed-based approach, we then demonstrated that Nx4 significantly enhanced the negative connectivity between the left CeMA and two cortical regions: the dorsolateral and medial prefrontal cortices. Conclusions: In a resting-state condition, Nx4 reduced the prefrontal cortex gFCD and strengthened the functional coupling between the amygdala and the prefrontal cortex that is relevant for emotion regulation and the stress response. Further studies should elaborate whether this mechanism represents enhanced regulatory control of the amygdala at rest and, consequently, to a diminished susceptibility to stress. ClinicalTrials.gov ID: NCT02602275.

Dataset Information

Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

Publications

Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

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