Disrupted functional connectivity of the brain reward system in substance use problems: a meta-analysis of functional neuroimaging studies
Bibliographic record
Abstract
ABSTRACT Importance Extensive 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. Objective To 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 Sources Identification 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 Selection Guidelines 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 Synthesis Spatially 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 Measures Identification of deficits in functional brain connectivity with the reward system across studies on substance use problems. Results Ninety-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 Relevance The 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 POINTS Question What functional brain connectivities with the brain reward system are reliably disrupted across studies on substance use problems? Findings Subjects 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. Meaning Deficient functional brain connectivity along the cortico-striato-thalamocortical loops may reflect deficits in habit formation, socio-emotional and salience processing in addiction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.018 | 0.040 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.038 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".