This analysis of fMRI data (n=15) examined how LSD (75μg) affects local brain activity and connectivity, finding that LSD decreased both measures in somatosensory/visual areas, with additional activity decreases in Default Mode and Fronto-Parietal networks and connectivity decreases in subcortical regions, with these changes occurring primarily in brain regions with high densities of D2 and 5HT1a receptors, suggesting complex neurobiological mechanisms underlying LSD's effects.
Despite a renewed scientific interest in lysergic acid diethylamide (LSD), its local neurofunctional effects remain underexplored. This functional Magnetic Resonance Imaging (fMRI) study explored and compared LSD-induced changes in local activity (amplitude of low-frequency fluctuations: ALFF) and local connectivity (regional homogeneity: ReHo), assessing their relationship to regional receptor density. Imaging data of 15 healthy adults from an open dataset were analyzed. For each participant, two pairs of resting-state runs were available (rest1 and rest2), one performed under placebo and one following the intravenous administration of 75μg LSD. Voxel-wise paired t-tests compared ALFF and ReHo in the LSD versus placebo conditions. Rest1*rest2 test-retest reliability and ALFF*ReHo cross-modal associations were assessed with conjunction maps and vertex-wise correlations. Finally, neurochemical enrichment analyses related LSD-induced ALFF and ReHo changes to cortical density maps of LSD-related neurotransmitter receptors and transporters. Both ALFF and ReHo decreased in somatosensory/visual cortices under LSD compared to placebo. Specific decreases were observed for ALFF in associative regions belonging to the Default Mode and Fronto-Parietal networks, and for ReHo in subcortical regions (cluster-based corrected p<0.05). Test-retest reliability was high for ALFF (rho=0.80, p=0.001) and moderate for ReHo (rho=0.46, p=0.001). ALFF*ReHo LSD-induced changes were moderately associated (rest1: rho=0.36, p=0.001; rest2: rho=0.56 p=0.001). Neurochemical enrichment analysis showed that LSD-induced ALFF/ReHo alterations occurred in regions with high density for D2 and 5HT1a receptors (FDR-corrected p<0.05). Together, interactions between reliable neurofunctional indexes and D2 and 5HT1a receptor densities unravel the involvement of novel, complex, and dynamic processes triggered by LSD.
Create a free account to open full-text PDFs.