The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli

Abstract

BackgroundThe cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. MethodsWe conducted multiple coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N=196 articles) involving drug (n=133) or natural reward-related (n=63) visual stimuli. Subsequently, we characterized the connectivity profiles of identified brain regions by using them as seeds in task-independent and task-dependent functional connectivity analyses. Using hierarchical clustering on these connectivity profiles, we grouped cue-related brain regions into subnetworks. Functional decoding was then employed to characterize mental operations linked with each subnetwork. ResultsAcross all studies, pooled activity convergence was observed in the striatum, amygdala, thalamus, cingulate, insula, and multiple frontal, parietal, and occipital regions. Drug-distinct convergence (drug>natural) was observed notably in the posterior cingulate cortex (PCC), dorsolateral prefrontal cortex (dlPFC), and temporal and parietal regions, whereas distinct natural reward convergence (natural>drug) was observed in thalamic, insular, orbitofrontal, and occipital regions. Hierarchical clustering using each regions connectivity profiles identified six subnetworks, involving: 1) occipital and thalamic (lateral geniculate nucleus) regions functionally linked with early visual processing, 2) occipital-temporal regions associated with higher level visual association, 3) parietal-frontal regions linked with cognitive control mechanisms, 4) posterior and ventral insula as well as anterior cingulate cortex (ACC) functionally linked with salient event detection, 5) nucleus accumbens, PCC, precuneus, ACC, and thalamus (mediodorsal) associated with subjective valuation, and 6) bilateral amygdalae, orbitofrontal, and dorsal insula regions linked with affective processes. ConclusionsThese outcomes suggest multifaceted brain activity during the cue-reactivity paradigm can be decomposed into more elemental processes and indicate that while drugs of abuse usurp the brains natural reward processing system, some regions appear distinctly related to drug cue-reactivity (e.g., PCC, dlPFC).