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Delay discounting differences in brain activation, connectivity, and structure in individuals with addiction: a systematic review protocol.

ABSTRACT: Delayed reward discounting (DRD), the degree to which future rewards are discounted relative to immediate rewards, is used as an index of impulsive decision-making and has been associated with a number of problematic health behaviors. Given the robust behavioral association between DRD and addictive behavior, there is an expanding literature investigating the differences in the functional and structural correlates of DRD in the brain between addicted and healthy individuals. However, there has yet to be a systematic review which characterizes differences in regional brain activation, functional connectivity, and structure and places them in the larger context of the DRD literature. The objective of this systematic review is to summarize and critically appraise the existing literature examining differences between addicted and healthy individuals in the neural correlates of DRD using magnetic resonance imaging (MRI) or functional magnetic resonance imaging (fMRI).A systematic search strategy will be implemented that uses Boolean search terms in PubMed/MEDLINE and PsycINFO, as well as manual search methods, to identify the studies comprehensively. This review will include studies using MRI or fMRI in humans to directly compare brain activation, functional connectivity, or structure in relation to DRD between addicted and healthy individuals or continuously assess addiction severity in the context of DRD. Two independent reviewers will determine studies that meet the inclusion criteria for this review, extract data from included studies, and assess the quality of included studies using the Grading of Recommendations Assessment, Development and Evaluation framework. Then, narrative review will be used to explicate the differences in structural and functional correlates of DRD implicated by the literature and assess the strength of evidence for this conclusion.This review will provide a needed critical exegesis of the MRI studies that have been conducted investigating brain differences in addictive behavior in relation to healthy samples in the context of DRD. This will provide clarity on the elements of neural activation, connectivity, and structure that are most implicated in the differences in DRD seen in addicted individuals.PROSPERO CRD42017056857.

SUBMITTER: Owens MM

PROVIDER: S-EPMC5504789 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:Individual differences in delay discounting-how much we discount future compared to immediate rewards-are associated with general life outcomes, psychopathology, and obesity. Here, we use machine learning on fMRI activity during an intertemporal choice task to develop a functional brain marker of these individual differences in human adults. Training and cross-validating the marker in one dataset (Study 1, N = 110 male adults) resulted in a significant prediction-outcome correlation (r = 0.49), generalized to predict individual differences in a completely independent dataset (Study 2: N = 145 male and female adults, r = 0.45), and predicted discounting several weeks later. Out-of-sample responses of the functional brain marker, but not discounting behavior itself, differed significantly between overweight and lean individuals in both studies, and predicted fasting-state blood levels of insulin, c-peptide, and leptin in Study 1. Significant predictive weights of the marker were found in cingulate, insula, and frontoparietal areas, among others, suggesting an interplay among regions associated with valuation, conflict processing, and cognitive control. This new functional brain marker is a step toward a generalizable brain model of individual differences in delay discounting. Future studies can evaluate it as a potential transdiagnostic marker of altered decision-making in different clinical and developmental populations.SIGNIFICANCE STATEMENT People differ substantially in how much they prefer smaller sooner rewards or larger later rewards such as spending money now versus saving it for retirement. These individual differences are generally stable over time and have been related to differences in mental and bodily health. What is their neurobiological basis? We applied machine learning to brain-imaging data to identify a novel brain activity pattern that accurately predicts how much people prefer sooner versus later rewards, and which can be used as a new brain-based measure of intertemporal decision-making in future studies. The resulting functional brain marker also predicts overweight and metabolism-related blood markers, providing new insight into the possible links between metabolism and the cognitive and brain processes involved in intertemporal decision-making.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is associated with atypical fronto-subcortical neural circuitry and heightened delay discounting, or a stronger preference for smaller, immediate rewards over larger, delayed rewards. Recent evidence of ADHD-related sex differences in brain structure and function suggests anomalies in fronto-subcortical circuitry may differ among girls and boys with ADHD. The current study examined whether the functional connectivity (FC) within fronto-subcortical neural circuitry differs among girls and boys with ADHD compared to same-sex typically developing (TD) controls and relates to delay discounting.MethodsParticipants include 8-12-year-old children with ADHD (n?=?72, 20 girls) and TD controls (n?=?75, 21 girls). Fronto-subcortical regions of interest were functionally defined by applying independent component analysis to resting-state fMRI data. Intrinsic FC between subcortical components, including the striatum and amygdala, and prefrontal components, including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and anterior dorsolateral prefrontal cortex (dlPFC), was compared across diagnostic groups overall and within sex. Correlations between intrinsic FC of the six fronto-subcortical pairs and delay discounting were also examined.ResultsBoth girls and boys with ADHD show atypical FC between vmPFC and subcortical regions including the striatum (stronger positive FC in ADHD) and amygdala (weaker negative FC in ADHD), with the greatest diagnostic effects among girls. In addition, girls with ADHD show atypical intrinsic FC between the striatum and dlPFC components, including stronger positive FC with ACC and stronger negative FC with dlPFC. Further, girls but not boys, with ADHD, show heightened real-time delay discounting. Brain-behavior correlations suggest (1) stronger negative FC between the striatal and dlPFC components correlated with greater money delay discounting across all participants and (2) stronger FC between the amygdala with both the dlPFC and ACC components was differentially related to heightened real-time discounting among girls and boys with and without ADHD.ConclusionsOur findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion.

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Delay discounting differences in brain activation, connectivity, and structure in individuals with addiction: a systematic review protocol.

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