Regional and cannabis-related differences in prefrontal multiscale entropy of resting-state EEG

• Frequent cannabis use is linked to reduced prefrontal complexity at coarse scales. • Prefrontal cortex shows lower multiscale entropy than other regions in healthy adults. • Multiscale entropy reveals scale-dependent cortical organization beyond power. Entropy analysis of electroencephalographic (EEG) data provides insight into the complexity of neural activity. This study primarily examined whether cannabis use frequency is associated with alterations in multiscale entropy (MSE) in the prefrontal cortex (PFC) and mapped baseline MSE differences across cortical regions. Resting-state EEG was collected from 57 adults: non-users (n = 18), low-frequency users (≤ 1×/week; n = 24), and frequent users (≥ 2×/week; n = 15). MSE values were binned into fine, medium, coarse, and very-coarse scale ranges. Linear mixed-effects models assessed group × scale bin interactions in the PFC and regional differences among lobes, irrespective of cannabis use. Entropy increased with coarser scales in all groups, but the slope was significantly flatter in frequent users. From the medium bin onward, their PFC scale–entropy slope was ∼ 0.12 bits lower than in non-users, widening to ∼ 0.16 bits at very-coarse scales (FDR-corrected q < 0.012). Across all participants, the PFC exhibited lower MSE than parietal, occipital, and temporal lobes, with regional gaps expanding at coarser scales. The PFC exhibits intrinsically reduced signal complexity compared with other cortical regions, with further attenuation in frequent cannabis users. MSE captures regional cortical dynamics in resting EEG and detects cannabis-related reductions in prefrontal signal complexity at longer temporal scales.