Acute and Chronic Effects of Betel Quid Chewing on Brain Functional Connectivity

Abstract

Background: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear.

Methods: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis.

Results: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus).

Conclusion: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus.

Keywords: arecoline; basal ganglia; betel quid; functional brain imaging; orbitofrontal cortex; resting-state fMRI.

Figure 1

(A) Network-based functional connectivity differences after acute administration of betel quid to naive participants. Orange indicates an increase in functional connectivity which was found between the subcortical and occipital brain regions. (B) The degree of different areas for acute use (ROIs with the highest degree). CAU, caudate; L/R, left/right; MOG, middle occipital gyrus; PUT, putamen; SOG, superior occipital gyrus; THA, thalamus.

Figure 2

The t map (link-wise FDR corrected, q=0.05) in Healthy Controls before and after acute betel quid chewing. A significant difference was detected with connectivity between the caudate and putamen. The colorbar represents the t value for each region of interest (ROI).

Figure 3

(A) Network-based connection differences for chronic betel quid users minus controls. Orange indicates an increase in functional connectivity which was found between the frontal, parietal and temporal brain regions. (B) The degree of different areas for chronic use [regions of interest (ROIs) with the highest degree] The right OFCmed is the combination of the sum degree of rectus, OFCmed, OFCant, and OFCpost). ANG, angular gyrus; ant/post, anterior/posterior; ITG, inferior temporal gyrus; L/R, left/right; med/lat, medial/lateral; OFC, orbitofrontal cortex; SFG, superior frontal gyrus; SPG, superior parietal gyrus.