Testing the role of the posterior cingulate cortex in processing salient stimuli in cannabis users: an rTMS study.

The posterior cingulate cortex (PCC) and precuneus are hubs in the default mode network and play a role in processing external salient stimuli. Accordingly, activation in these regions has been associated with response to salient stimuli using drug cue-reactivity paradigms in substance using populations. These studies suggest that the PCC and precuneus may underlie deficits in processing salient stimuli that contribute toward the development of substance use disorders. The goal of this study was to directly test this hypothesis using repetitive transcranial magnetic stimulation (rTMS). Using a double-blind, placebo-controlled design, we used rTMS to target the PCC and precuneus with a double-cone coil at 10 Hz (high frequency) and 1 Hz (low frequency) in 10 adult cannabis users and 10 age- and sex-matched non-using controls. Electroencephalography data were collected before and after rTMS during a modified oddball paradigm with neutral, oddball, self-relevant, and cannabis-related stimuli. Cannabis users exhibited increased amplitude in P3 and faster latencies in the P3, N2, and P2 components in response to self-relevant stimuli compared to controls during baseline that normalized after rTMS. These results suggest that cannabis users exhibited heightened salience to external self-relevant stimuli that were modulated after rTMS. PCC dysfunction in cannabis users may be related to abnormalities in processing salient stimuli, such those during cue-reactivity, and provides a potential target for cannabis use disorder intervention.

Cannabis users exhibit increased cortical activation during resting state compared to non-users.

Studies have shown altered task-based brain functioning as a result of cannabis use. To date, however, whether similar alterations in baseline resting state and functional organization of neural activity are observable in cannabis users remains unknown. We characterized global resting state cortical activations and functional connectivity via electroencephalography (EEG) in cannabis users and related these activations to measures of cannabis use. Resting state EEG in the eyes closed condition was collected from age- and sex-matched cannabis users (N = 17; 6 females; mean age = 30.9 ±â€¯7.4 years) and non-using controls (N = 21; 9 females; mean age = 33.1 ±â€¯11.6 years). Power spectral density and spectral coherence were computed to determine differences in cortical activations and connectivity between the two groups in the delta (1-4Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-50 Hz) frequency bands. Cannabis users exhibited decreased delta and increased theta, beta, and gamma power compared to controls, suggesting increased cortical activation in resting state and a disinhibition of inhibitory functions that may interrupt cognitive processes. Cannabis users also exhibited increased interhemispheric and intrahemispheric coherence relative to controls, reduced mean network degree, and increased clustering coefficient in specific regions and frequencies. This increased cortical activity may indicate a loss of neural refinement and efficiency that may indicate a "noisy" brain. Lastly, measures related to cannabis use were correlated with spectral power and functional connectivity measures, indicating that specific electrophysiological signals are associated with cannabis use. These results suggest that there are differences in cortical activity and connectivity between cannabis users and non-using controls in the resting state that may be related to putative cognitive impairments and can inform effectiveness of intervention programs.