Regular cannabis use modulates gamma functional connectivity with V1 during visual processing

Cannabis is a widely-used illicit substance in the United States, and heavy cannabis use has been linked to deficits across multiple cognitive domains. Mechanistically, cannabis affects endocannabinoid receptors densely distributed among GABAergic interneurons throughout the cortex and cerebellum. Such interneuronal networks are known to be crucial in the generation of fast neural gamma-band responses, which support perceptual and cognitive processing and have been frequently implicated in cannabis use. However, studies to date have tended to focus on higher-order processing supported by gamma oscillations, with limited work examining more fundamental aspects of gamma circuit integrity. Herein, 84 adults who regularly use cannabis and 90 demographically-matched nonusers underwent high-density magnetoencephalography during a visual entrainment task involving three gamma-band flicker frequencies (32, 40, and 48 Hz). The resulting data were imaged in the time-frequency domain and the dynamic neural time series were extracted and tested for effects of hemisphere, frequency, and group, and then used to compute whole-brain dynamic functional connectivity. Our results indicated strong gamma entrainment in the bilateral primary visual cortices (V1), with 32 Hz responses being the strongest across both groups (p < .001) and right V1 activity being stronger than left across groups and frequencies (p = .002). Additionally, there were group-by-condition interactions in connectivity maps (p < .005), with the cannabis group having elevated 32 Hz connectivity between V1 and higher-order visual regions relative to controls. These findings suggest that basic gamma circuitry remains intact despite heavy cannabis use, while gamma functional connectivity is preferentially affected and this may lead to the higher-order deficits.