INTRODUCTION: With the advent of advanced neuroimaging, strides have been made towards better understanding the cognitive elements necessary for task processing. Resting state functional connectivity assessments using functional magnetic resonance imaging has allowed patient assessments of underlying neural networks in patient populations with variable constraints. Drug addiction, a chronically relapsing disorder, presents many variable constraints. Cellular and molecular changes in neural reward pathway of drug addicted patient populations have advanced, but circuit-level alterations with reward deficits are yet to be completely understood. Resting state functional connectivity investigations in patient populations that use illicit drugs are seen to have repercussions on neural networks. OBJECTIVE: Assess and compare reward-network resting state functional connectivity investigations in patient populations with illicit drug use. METHODS: A meta-analysis of several resting state functional connectivity studies. Patient populations for each study contained an experimental group of drug users with a group of non-drug using controls to assess changes in resting state functional connectivity of the reward network. Studies utilized Diagnostic and Statistical Manuel of Mental disorders, 4th edition, as the basis of diagnosing drug dependence and abuse. A 3 Tesla MRI scanner was utilized to assess the reward pathway of the drug abuse in all experiments with the exception of one group using a 4 Tesla scanner. Band-pass temporal filtering from roughly 0.01 Hz to 0.1 Hz on residual signals was used to obtain low-frequency fluctuations needed for resting state connectivity analyses. Correlation maps were created by computing the correlation coefficients between the blood oxygen level dependent time course from the seed regions and from all other brain voxels. Regions of interest were chosen based on data from databases or previous studies. RESULTS: Four papers found widespread reductions in the connectivity of multiple reward pathway components. Results of these studies are consistent with perspectives suggesting that transition from drug use to addiction is driven by reduced functioning of reward systems and concurrently increased activation of anti-reward systems. Two studies suggested an increase in reward pathway of drug use, suggesting enhanced connectivity within reward and motivation circuits may be interpreted in the perspective of altered incentive salience for drugs and drug-associated stimuli. CONCLUSION: At early stage of experimental data in this field, data interpretation necessitates caution. Small sample sizes, heterogeneous subject groups and variable experimental paradigms may have lead to opposing findings. With certainty, chronic drug use was found to alter reward pathway in patient populations.

Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n= 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterized post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and ΔFosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.