Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note.

Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) "Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)". Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.

Neurophysiologic Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) via Electrical Stimulation of the Tragus: A Concurrent taVNS/fMRI Study and Review.

(Appeared originally in Brain Stimulation 2018; 11:492-500) Reprinted with permission from Elsevier.

Moving 2 Mindful (M2M) study protocol: testing a mindfulness group plus ecological momentary intervention to decrease stress and anxiety in adolescents from high-conflict homes with a mixed-method longitudinal design.

INTRODUCTION: Interparental conflict exposure places adolescents at risk for problems with stress and anxiety; existing prevention/intervention strategies focus on reducing interparental conflict. Mindfulness-based programmes may be a promising treatment strategy for this population, but studies have not yet tested whether they are effective in this high-conflict context. In addition, evidence suggests that extensions to traditional treatments, such as delivering components in daily life that are tailored to moments of need, can increase treatment efficacy, particularly when combined with in-person treatments and particularly for adolescents. However, there are no such extensions to mindfulness interventions available. The Moving 2 Mindful study aims to (1) develop an ecological momentary intervention (EMI) supplement to Learning to BREATHE (L2B), an evidence-based mindfulness intervention for adolescents; (2) refine the EMI programme and determine the best delivery plan; (3) examine the feasibility and acceptability of L2B Plus (L2B plus the developed supplement) and (4) examine the potential for L2B Plus to reduce stress and anxiety for adolescents from high-conflict homes. METHODS AND ANALYSIS: The Moving 2 Mindful study proposes a mixed-methods approach to developing and refining a multimethod adaptive supplement to L2B. Feasibility, acceptability and potential effectiveness will be tested in a sample of 38 families, who will be randomly assigned to receive L2B Plus or an active health and wellness control condition and followed until 3 months postintervention. A range of psychosocial and physiological factors will be assessed at multiple time points. This study is registered with clinicaltrials.gov (ID NCT03869749; pre-results). ETHICS AND DISSEMINATION: The Institutional Review Board at Colorado State University has approved this study. Findings will be disseminated in scientific journals and conferences, whether they are positive, negative or inconclusive.

Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review.

BACKGROUND: Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters. OBJECTIVE: We developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation. METHODS: We enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500 µs 25 HZ for 60 s (repeated 3 times over 6 min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted. RESULTS: Active stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate. CONCLUSION: Stimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.