Betel nut is one of the common addictive substances in many countries. The brain influence of cocaine, alcohol, and tobacco cigarette have been studied by several studies [1]. However, only few studies focused on the brain influence of betel nut, and most of them used fMRI or PET. Thus, our study aim was to use diffusion tensor imaging (DTI) to evaluate the impact of neurological structure of white matter caused by betel nut. The brain structural differences between the betel nut chewers (BNC) and healthy controls (HC) and the correlation with inhibitory control were also discussed.

All participants, including 11 betel nut chewers and 13 healthy controls, were arranged for a brain DTI examination on a 3T imaging system (Skyra, Siemens, Germany). The DTI parameters included TR/TE = 4800/97 ms; voxel size = 2 x 2 x 4 mm³; 35 axial contiguous slices. 192 diffusion directions with b-values of 1000, 1500, 2000 s/mm² and 12 null images were performed and scan time was around 16.5 min.

The raw diffusion data for each participant were first corrected eddy current distortions using FMRIB (functional magnetic resonance imaging of the brains) Software Library (FSL). Each participant’s diffusion images were spatially normalized to the Montreal Neurological Institute (MNI) T2W template using parameters determined from the normalization of the diffusion null image to the T2W template using Statistical Parametric Mapping (SPM). DTI reconstruction was performed using DSI Studio, and it was capable of calculating the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) mapping. For the statistical analysis, a two sample t-test was used to detect the significant differences between the betel nut chewers and the healthy controls on the DTI indices. Finally, multiple regression was used to detect the correlation between the inhibitory control, stop-signal reaction time (SSRT), and the DTI indices for all participants. The higher the SSRT score, the worse inhibitory control.

Our results showed that higher FA and lower MD and RD were found in betel nut chewers' left insula compared to HCs (p < 0.05). Lower MD, AD and RD were found in betel nut chewers' amygdala and putamen (p < 0.05) (Fig. 1). In addition, the positive correlation between SSRT and FA of left insula (p < 0.05) and right putamen (p < 0.005) were found (Fig. 2).

In our results, higher FA and lower MD and RD in the insula of the betel nut chewers were found. Insula plays the role in conscious urges of taking drugs. Lots of functional imaging studies have shown that the activity of insula was related to urges [2]. One study compared two kinds of smokers. They found that smokers with brain damage involving the insula were >100 times more likely than smokers with brain damage not involving the insula to undergo a ‘disruption of smoking addiction’, characterized by the ability to quit smoking easily, immediately, without relapse and without a persistence of the urge to smoke [3].

In our results, low MD, AD and RD in the amygdala of the betel nut chewers were found. The stress system, including amygdala, was a key element of the addiction process. It produced the negative emotion that makes the intense motivation for drug-seeking [4]. In the amygdala, the effects of abusing addictive substances could be found in a series of in vivo microdialysis, and the counter-adaptation of brain reward system might active during the development of addiction dependence [5].

In our results, lower MD, AD and RD in the putamen of the betel nut chewers were found. In the study of neuroimaging on internet addiction [6], the activated region was comparatively large in the experimental group in several brain regions, including putamen. It demonstrated that addicts may have brain dysfunction, and compensatory mechanism was needed to maintain normal brain function.

The positive correlation between SSRT and FA indicated worse inhibitory control caused the urge of addiction in insula and the compensatory mechanism of addiction in putamen.

Our results pointed out the significant neurological structural differences in the insula, amygdala and putamen of DTI indices between the betel nut chewers and HCs. Chewing betel nut is a major cause of oral cancer in many countries. The study gave us the opportunity to “visualize” the habitual betel nut chewers’ addictive brains. The DTI images provided important insight to the researchers and the clinicians as to develop an effective abstinence treatment for these chewers.