Salience network structural integrity predicts executive impairment in alcohol use disorders

Abstract

The neural bases of cognitive impairment(s) in alcohol use disorders (AUDs) might reflect either a global brain damage underlying different neuro-cognitive alterations, or the involvement of specific regions mostly affected by alcohol neuro-toxic effects. While voxel-based-morphometry (VBM) studies have shown a distributed atrophic pattern in fronto-limbic and cerebellar structures, the lack of comprehensive neuro-cognitive assessments prevents previous studies from drawing robust inferences on the specificity of the association between neuro-structural and cognitive impairments in AUDs. To fill this gap, we addressed the neuro-structural bases of cognitive impairment in AUDs, by coupling VBM with an in-depth neuropsychological assessment. VBM results highlighted a diffuse pattern of grey matter reduction in patients, involving the key-nodes of the meso-cortico-limbic (striatum, hippocampus, medial prefrontal cortex), salience (insular and dorsal anterior cingulate cortex) and executive (inferior frontal cortex) networks. Grey matter density in the insular and anterior cingulate sectors of the salience network, significantly decreased in patients, explained almost half of variability in their defective attentional and working-memory performance. The multiple cognitive and neurological impairments observed in AUDs might thus reflect a specific executive deficit associated with the selective damage of a salience-based neural mechanism enhancing access to cognitive resources required for controlled cognition and behaviour.

Figure 1

Grey-matter density reduction in AUDs. The brain regions in which grey matter density was (A) significantly reduced in AUD patients vs. controls; (B) positively correlated with executive performance; (C) negatively correlated with TMT-A response time (p < 0.025 corrected for multiple comparisons).

Figure 2

Correlation between grey-matter density and executive performance in AUDs. The brain regions in which grey matter density was (A) both significantly reduced in AUD patients vs. controls and positively correlated with executive performance; (B) both significantly reduced in AUD patients vs. controls and negatively correlated with TMT-A response time (p < 0.025 corrected for multiple comparisons). The scatterplots in panel (A) additionally depict the relationship between executive performance and average grey matter density in the left and right fronto-insular cortex, either in healthy controls (HC), alcoholic patients (PT) or both.

Figure 3

Common neuro-structural effects of AUDs and correlation with executive performance. The brain regions showing specific vs. common effects of AUDs, executive performance or TMT-A response time (p < 0.025 corrected for multiple comparisons).

Figure 4

Salience network and executive impairment in AUDs. The overlap between the salience network (red) and the brain regions showing common effects of AUDs and either executive performance (blue) or TMT-A response time (green). The scatterplots depict the significant relationship between average grey matter density in the overlapping voxels (white colour) and either executive performance (left) or TMT-A response time (right).