Aberrant inhibitory processing in the somatosensory cortices of cannabis-users

Abstract

Background: Delta-9 tetrahydrocannabinol (THC) is a major exogenous psychoactive agent, which acts as a partial agonist on cannabinoid (CB₁) receptors. THC is known to inhibit presynaptic neurotransmission and has been repeatedly linked to acute decrements in cognitive function across multiple domains. Previous electrophysiological studies of sensory gating have shown specific deficits in inhibitory processing in cannabis-users, but to date these findings have been limited to the auditory cortices, and the degree to which these aberrations extend to other brain regions remains largely unknown.

Methods: We used magnetoencephalography (MEG) and a paired-pulse somatosensory stimulation paradigm to probe inhibitory processing in 29 cannabis-users (i.e. at least four times per month) and 41 demographically matched non-user controls. MEG responses to each stimulation were imaged in both the oscillatory and time domain, and voxel time-series data were extracted to quantify the dynamics of sensory gating, oscillatory gamma activity, evoked responses, and spontaneous neural activity.

Results: We observed robust somatosensory responses following both stimulations, which were used to compute sensory gating ratios. Cannabis-users exhibited significantly impaired gating relative to non-users in somatosensory cortices, as well as decreased spontaneous neural activity. In contrast, oscillatory gamma activity did not appear to be affected by cannabis use.

Conclusions: We observed impaired gating of redundant somatosensory information and altered spontaneous activity in the same cortical tissue in cannabis-users compared to non-users. These data suggest that cannabis use is associated with a decline in the brain's ability to properly filter repetitive information and impairments in cortical inhibitory processing.

Keywords: CUDIT; Magnetoencephalography; inter-stimulus interval; spontaneous neural activity; time-domain.

Fig. 1.

Group differences in the time-domain somatosensory gating response. (A) The time domain averaged data of each group extracted from the peak voxel of grand-averaged sLORETA source images showed robust responses to each stimulation. The x-axis denotes time in ms, while power in arbitrary units is represented on the y-axis. The grand-averaged time-domain map, collapsed across both stimulations and groups, is shown in the top left corner. (B) Independent samples t-tests revealed a higher gating ratio (i.e., impaired gating) in cannabis users (shown in red) compared to the nonuser controls (shown in blue). Notably, the response power between the two groups did not differ significantly either to stimulation 1 (C) or 2 (D). Error bars reflect the SEM. *p < .05.

Fig. 2.

Time-frequency responses to somatosensory stimulation of the right median nerve. (A): Time-frequency spectrogram from a MEG sensor near the sensorimotor cortices with time indicated in ms on the x-axis and frequency in Hz on the y-axis. Stimulations occurred at 0 and 500 ms. The percent change from baseline is indicated by the color bar on the right. (B): Group averaged beamformer images (pseudo-t) for stimulation 1 (left), stimulation 2 (middle), and the group's grand-average (right). Strong increases in power were found in virtually identical areas of the contralateral hand region of the somatosensory cortex in nonuser controls (upper panel) and cannabis users (lower panel). These maps were grand averaged across both stimulations and groups to identify the peak voxel, which was followed by virtual sensor extraction and additional analyses.

Fig. 3.

Spontaneous neural activity. (A): Absolute voxel time series envelope extracted from the peak voxel and averaged across the 30-75 Hz range in each group, with the gray window highlighting the baseline period. (B): Independent samples t-tests of the baseline period (gray window; −700 to −300 ms) revealed significantly reduced spontaneous gamma activity in cannabis-users (red) relative to the nonuser controls (blue). *p < .05.