Disrupted functional connectivity of the brain reward system in substance use problems: a meta-analysis of functional neuroimaging studies

ABSTRACTImportanceExtensive literature suggests that the brain reward system is crucial in understanding the neurobiology of substance use disorders. However, across studies on substance use problems, evidence of reliable disruptions in functional connectivity is limited.ObjectiveTo uncover deficient functional connectivity with the brain reward system that are reliably associated with substance use problems, by meta-analytically synthesizing results of functional brain connectivity studies on substance use problems.Data SourcesIdentification of relevant functional brain connectivity studies on substance misuse was done using PubMed, Google Scholar and EMBASE (until September 2021) with the following terms: cannabis, cocaine, substance, methamphetamine, amphetamine, alcohol, tobacco, nicotine, functional connectivity, resting-state, task-based connectivity, psychophysiological interaction.Study SelectionGuidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed, Publications were included if they reported stereotactic coordinates of functional brain connectivity results on individuals with substance use problems without a comorbid major mental illness or organic impairment.Data Extraction and SynthesisSpatially convergent brain regions across functional connectivity studies on subjects with substance use problems were analyzed using Activation Likelihood Estimation meta-analysis.Altered connectivity with regions of the brain reward system was performed carried out through voxelwise seed-based meta-analyses. Subanalyses were performed to examine mediating factors such as severity of illness, connectivity modalities and types of substances.Main Outcomes and MeasuresIdentification of deficits in functional brain connectivity with the reward system across studies on substance use problems.ResultsNinety-six studies using a seed-based connectivity approach were included, representing 5757 subjects with substance use problems. In subjects with substance use problems, the ventromedial prefrontal cortex exhibited hyperconnectivity with the ventral striatum, and hypoconnectivity with the amygdala and hippocampus. Executive striatum showed hyperconnectivity with motor thalamus and dorsolateral prefrontal cortex, and hypoconnectivity with anterior cingulate cortex and anterior insula. Finally, the limbic striatum was found to be hyperconnected to the orbitofrontal cortex, and hypoconnected to the precuneus, compared to healthy subjects.Conclusions and RelevanceThe current study provided meta-analytical evidence of deficient functional connectivity between brain regions of the reward system and cortico-striato-thalamocortical loops in addiction, in line with current influential neurobiological models. These results are consistent with deficits in motivation and habit formation occurring in addiction, and they also highlight alterations in brain regions involved in socio-emotional processing and attention salience.KEY POINTSQuestionWhat functional brain connectivities with the brain reward system are reliably disrupted across studies on substance use problems?FindingsSubjects with substance use problems exhibited deficient connectivity between the ventromedial prefrontal cortex and subcortical structures including the ventral striatum, amygdala, and hippocampus. Executive striatum showed hyperconnectivity with motor thalamus and dorsolateral prefrontal cortex, and hypoconnectivity with anterior cingulate cortex and anterior insula. Altered connectivity between limbic striatum and core regions of the default mode network was also observed.MeaningDeficient functional brain connectivity along the cortico-striato-thalamocortical loops may reflect deficits in habit formation, socio-emotional and salience processing in addiction.

Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System

A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.

Blunted reward prediction error signals in internet gaming disorder

Background Internet gaming disorder (IGD) is a type of behavioural addictions. One of the key features of addiction is the excessive exposure to addictive objectives (e.g. drugs) reduces the sensitivity of the brain reward system to daily rewards (e.g. money). This is thought to be mediated via the signals expressed as dopaminergic reward prediction error (RPE). Emerging evidence highlights blunted RPE signals in drug addictions. However, no study has examined whether IGD also involves alterations in RPE signals that are observed in other types of addictions. Methods To fill this gap, we used functional magnetic resonance imaging data from 45 IGD and 42 healthy controls (HCs) during a reward-related prediction-error task and utilised a psychophysiological interaction (PPI) analysis to characterise the underlying neural correlates of RPE and related functional connectivity. Results Relative to HCs, IGD individuals showed impaired reinforcement learning, blunted RPE signals in multiple regions of the brain reward system, including the right caudate, left orbitofrontal cortex (OFC), and right dorsolateral prefrontal cortex (DLPFC). Moreover, the PPI analysis revealed a pattern of hyperconnectivity between the right caudate, right putamen, bilateral DLPFC, and right dorsal anterior cingulate cortex (dACC) in the IGD group. Finally, linear regression suggested that the connection between the right DLPFC and right dACC could significantly predict the variation of RPE signals in the left OFC. Conclusions These results highlight disrupted RPE signalling and hyperconnectivity between regions of the brain reward system in IGD. Reinforcement learning deficits may be crucial underlying characteristics of IGD pathophysiology.