Regular cannabis use modulates gamma activity in brain regions serving motor control

Abstract

Background: People who regularly use cannabis exhibit altered brain dynamics during cognitive control tasks, though the impact of regular cannabis use on the neural dynamics serving motor control remains less understood.

Aims: We sought to investigate how regular cannabis use modulates the neural dynamics serving motor control.

Methods: Thirty-four people who regularly use cannabis (cannabis+) and 33 nonusers (cannabis-) underwent structured interviews about their substance use history and performed the Eriksen flanker task to map the neural dynamics serving motor control during high-density magnetoencephalography (MEG). The resulting neural data were transformed into the time-frequency domain to examine oscillatory activity and were imaged using a beamforming approach.

Results: MEG sensor-level analyses revealed robust beta (16-24 Hz) and gamma oscillations (66-74 Hz) during motor planning and execution, which were imaged using a beamformer. Both responses peaked in the left primary motor cortex and voxel time series were extracted to evaluate the spontaneous and oscillatory dynamics. Our key findings indicated that the cannabis+ group exhibited weaker spontaneous gamma activity in the left primary motor cortex relative to the cannabis- group, which scaled with cannabis use and behavioral metrics. Interestingly, regular cannabis use was not associated with differences in oscillatory beta and gamma activity, and there were no group differences in spontaneous beta activity.

Conclusions: Our findings suggest that regular cannabis use is associated with suppressed spontaneous gamma activity in the left primary motor cortex, which scales with the degree of cannabis use disorder symptomatology and is coupled to behavioral task performance.

Keywords: Cannabis use; gamma; magnetoencephalography; motor control; motor cortex.

Figure 1.. Experimental Paradigm and Behavioral Results.

(A) An illustration of the flanker arrow paradigm. Each trial had a fixation period lasting on average 1500 ms (variable ISI: 1450–1550 ms) and a stimulus-presentation period lasting 2500 ms, which consisted of one of the four options displayed. (B) Reaction time (in ms) is displayed on the y-axis with group status on the x-axis, comparing behavior across trial conditions. Both groups exhibited a significant condition effect (i.e., flanker effect), but there was not a significant main effect of group nor significant group-by-condition interaction. *p < .05.

Figure 2.. Neural oscillatory responses during motor control.

(A): Grand-averaged time-frequency spectrogram of an MEG sensor across all participants exhibiting a significant gamma response (top; 66–74 Hz, −25 to 175 ms) and beta ERD (bottom; 16–24 Hz, −300 to 300 ms). The spectrogram displays frequency (Hz) on the y-axis, and time (ms) on the x-axis. Signal power is expressed as a percent difference from the baseline period, with the color legend shown to the right of the spectrogram. Note that the post-movement beta rebound (PMBR) response can also be seen, but this was not further examined since it happened after the movement, and we were interested in the impact of cognitive features of the task and stimuli on motor control. (B-C) Time-frequency spectrograms are also shown separately for the cannabis− (B) and cannabis+ (C) groups. (D): Grand-averaged beamformer images (pseudo-t) across both conditions and all participants for each significant time-frequency component.

Figure 3.. Conditional differences in oscillatory gamma power in the left primary motor cortex.

Peak voxel time series were extracted from the left primary motor cortex (M1) to quantify the dynamics of the gamma ERS response. There was a main effect of task condition (p = .024), with gamma responses being stronger during incongruent relative to congruent trials. There was not a significant main effect of group, nor a group-by-condition interaction.

Figure 4.. Group differences in spontaneous gamma activity.

Peak voxel time series of the left primary motor cortex were extracted to estimate mean spontaneous gamma power during the baseline period (−1800 to −1000 ms), which significantly differed by group (p = .001). Specifically, people who regularly use cannabis (cannabis+) had significantly weaker spontaneous gamma activity during the baseline compared to people who do not use cannabis (cannabis-).

Figure 5.. Spontaneous gamma activity in the left primary motor cortex scales with cannabis use disorder symptomatology and reaction time.

(A) Higher scores on the CUDIT-R (i.e., greater cannabis use disorder symptoms) were associated with weaker spontaneous gamma activity during the baseline period in the left M1 (p = .014). (B) Weaker spontaneous baseline gamma activity in left M1 was also associated with faster reaction times in the flanker task across all participants (p = .04), with this effect being driven by the cannabis+ group. (C) There was a significant indirect effect in which greater cannabis use disorder symptomatology was associated with faster reaction times through a greater suppression in spontaneous gamma activity in the left M1 (β = −0.173, p = .049). *p < .05, **p < .005