Alcohol affects the brain's resting-state network in social drinkers

Abstract

Acute alcohol intake is known to enhance inhibition through facilitation of GABA(A) receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC) on standardized Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta bands (eyes-closed) following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo). Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as expected, to increased GABA transmission and functional connectivity, while long-term alcohol consumption may be linked to exactly the opposite effect.

Figure 1. Alcohol-induced significant connectivity differences.

Differences during eyes-open and during eyes-closed sessions are presented in the upper and lower panel respectively. Significantly (p<.05, FDR corrected) increased connectivity is shown in the upper rows (red connections), decreased in the lower rows (blue connections). The number of significantly affected connections is also presented for each frequency band.

Figure 2. Significant alcohol effect on graph parameters across different thresholds.

Double stars (**) indicate significant p-values (p<0.03), single stars (*) indicate marginally significant effects (p<0.06). To maintain the high resolution and quality of the figures, we did not include all the results for the many different thresholds, but only for the first seven. Characteristic path length, clustering coefficient, and consequently small-worldness are normalized by random surrogate graphs .

Figure 3. Scatter plot of global and local efficiency (threshold set to 0.35).

Averaged values are grouped for alcohol (red symbols) and placebo (blue symbols) for both eyes-open (left panel) and eyes-closed (right panel) sessions. Greek letters designate the frequency band studied accordingly. The corresponding values of 100 random graphs are represented with black dots.

Figure 4. Topologies of the nodes with increased degree following inebriation for a representative threshold of 0.35.

Left: The highlighted nodes have a degree significantly altered by alcohol intake (vs. placebo) in alpha band during eyes-open and in theta band during eyes-closed. The size of red nodes is inversely proportional to the significant (< .05) p-values: the larger the node the more significant the effect is. Right: Mean node degree values of the nodes significantly affected (p<.05) by alcohol for alpha band (upper row) and theta band (lower row) networks averaged across participants (± SD).

Figure 5. Correlation of SAC with the density of the networks for beta frequency band.

(A) Scatter plot of SAC values versus beta band density during the alcohol session; (B) To illustrate this correlation, the averaged functional networks of the 7 participants with the lowest and 7 participants with the highest SAC values are presented as weighted AMs. The weights of these AMs are the MSC values; (C) connections of the networks in (B), after being converted to binary graphs using a representative threshold of 0.35.