Mapping brain functional alterations in betel-quid chewers using resting-state fMRI and network analysis
- 147 Downloads
The World Health Organization regards betel quid (BQ) as a human carcinogen, and DSM-IV and ICD-10 dependence symptoms may develop with its heavy use. BQ’s possible effects of an enhanced reward system and disrupted inhibitory control may increase the likelihood of habitual substance use.
The current study aimed to employ resting-state fMRI to examine the hypothesized enhanced reward system (e.g., the basal forebrain system) and disrupted inhibitory control (e.g., the prefrontal system) in BQ chewers.
The current study recruited three groups of 48 male participants: 16 BQ chewers, 15 tobacco- and alcohol-user controls, and 17 healthy controls. We used functional connectivity (FC), mean fractional amplitude of low-frequency fluctuations (mfALFF), and mean regional homogeneity (mReHo) to evaluate functional alternations in BQ chewers. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the functional network differences among the three groups.
Our hypothesis was partially supported: the enhanced reward system for the BQ chewers (e.g., habitual drug-seeking behavior) was supported; however, their inhibitory control was relatively preserved. In addition, we reported that the BQ chewers may have enhanced visuospatial processing and decreased local segregation.
The current results (showing an enhanced reward system in the chewers) provided the clinicians with important insight for the future development of an effective abstinence treatment.
KeywordsBetel quid Resting-state functional MRI (rs-fMRI) Functional connectome Graph theoretical analysis (GTA) Network-based statistical (NBS) analysis
The authors would like to thank Jau-Yang Lin for his assistance in experimental preparation.
This study was supported by the research programs NSC103-2420-H-040-001-MY2, MOST105-2410-H-040-001-MY3, and MOST106-2221-E-182-079, which were sponsored by the Ministry of Science and Technology, Taipei, Taiwan.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Asthana S, Raffaele KC, Greig NH, Berardi A, Morris PP, Schapiro MB, Rapoport SI, Blackman MR, Soncrant TT (1995) Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer’s disease. Psychoneuroendocrinology 20(6):623–636. https://doi.org/10.1016/0306-4530(94)00084-N CrossRefPubMedGoogle Scholar
- Bullmore ET, Bassett DS (2011) Brain graphs: graphical models of the human brain connectome. Annu Rev Clin Psychol 7(1):113–140. https://doi.org/10.1146/annurev-clinpsy-040510-143934 CrossRefPubMedGoogle Scholar
- Chen CH, Chen WJ, Cheng AT (2005) New approach to the validity of the alcohol use disorders identification test: stratum-specific likelihood ratios analysis. Alcohol Clin Exp Res 29(4):602–608. https://doi.org/10.1097/01.ALC.0000159189.56671.EC CrossRefPubMedGoogle Scholar
- Chen VC, Shen CY, Liang SH, Li ZH, Tyan YS, Liao YT, Huang YC, Lee Y, McIntyre RS, Weng JC (2016) Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses. J Affect Disord 205:103–111. https://doi.org/10.1016/j.jad.2016.06.066 CrossRefPubMedGoogle Scholar
- Ersche KD, Williams GB, Robbins TW, Bullmore ET (2013) Meta-analysis of structural brain abnormalities associated with stimulant drug dependence and neuroimaging of addiction vulnerability and resilience. Curr Opin Neurobiol 23(4):615–624. https://doi.org/10.1016/j.conb.2013.02.017 CrossRefPubMedGoogle Scholar
- Everitt BJ, Cardinal RN, Hall J, Parkinson J, & Robbins T (2000) Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction. In: Aggleton JP (ed), The amygdala: a functional analysis, Oxford University Press, Oxford, p 353-390Google Scholar
- Gu H, Salmeron BJ, Ross TJ, Geng X, Zhan W, Stein EA, Yang Y (2010) Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity. NeuroImage 53(2):593–601. https://doi.org/10.1016/j.neuroimage.2010.06.066 CrossRefPubMedPubMedCentralGoogle Scholar
- Ho MC, Wang CK (2010) Can betel nut chewing affect the UFOV size after sleep deprivation? Chin J Psychol 52:445–456Google Scholar
- IARC (2004) Betel-quid and areca-nut chewing and some areca-nut-derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum, LyonGoogle Scholar
- Kim H, Kim YK, Gwak AR, Lim J-A, Lee J-Y, Jung HY, Sohn BK, Choi S-W, Choi J-S (2015) Resting-state regional homogeneity as a biological marker for patients with internet gaming disorder: a comparison with patients with alcohol use disorder and healthy controls. Prog Neuro-Psychopharmacol Biol Psychiatry 60:104–111. https://doi.org/10.1016/j.pnpbp.2015.02.004 CrossRefGoogle Scholar
- Ko YC, Chiang TA, Chang SJ, Hsieh SF (1992) Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med 21(6):261–264. https://doi.org/10.1111/j.1600-0714.1992.tb01007.x CrossRefPubMedGoogle Scholar
- Lee CH, Chiang SL, Ko AMS, Hua CH, Tsai MH, Warnakulasuriya S, Ibrahim SO, Zain RB, Ling TY, Huang CL (2014) Betel-quid dependence domains and syndrome associated with betel-quid ingredients among chewers: an Asian multi-country evidence. Addiction 109(7):1194–1204. https://doi.org/10.1111/add.12530 CrossRefPubMedGoogle Scholar
- Li RH, Ho MC, Tang TC, Chang CF (2012) Development of the betel nut dependency scale (BNDS). Chin J Psychol 54:331–348Google Scholar
- Liu T, Li J-j, Zhao Z-g, Zhong Y, Zhang Z-q, Xu Q, Yang G-s, Lu G-m, Pan S-y, Chen F (2016a) Betel quid dependence is associated with functional connectivity changes of the anterior cingulate cortex: a resting-state fMRI study. J Transl Med 14:1. https://doi.org/10.1186/s12967-016-0784-1 CrossRefGoogle Scholar
- MHW (2008) 905 betel nut chewing. Retrieved from https://www.mohw.gov.tw/dl-37747-2317188e-1f02-407b-a54a-ef4d0f663473.html
- Osborne PG, Ko Y-C, Wu M-T, Lee C-H (2017) Intoxication and substance use disorder to Areca catechu nut containing betel quid: a review of epidemiological evidence, pharmacological basis and social factors influencing quitting strategies. Drug Alcohol Depend 179:187–197. https://doi.org/10.1016/j.drugalcdep.2017.06.039 CrossRefPubMedGoogle Scholar
- Philip NS, Kuras YI, Valentine TR, Sweet LH, Tyrka AR, Price LH, Carpenter LL (2013) Regional homogeneity and resting state functional connectivity: associations with exposure to early life stress. Psychiatry Res 214(3):247–253. https://doi.org/10.1016/j.pscychresns.2013.07.013 CrossRefPubMedGoogle Scholar
- Raffaele KC, Asthana S, Berardi A, Haxby JV, Morris PP, Schapiro MB, Soncrant TT (1996) Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer’s disease. Neuropsychopharmacology 15(2):163–170. https://doi.org/10.1016/0893-133X(95)00179-H CrossRefPubMedGoogle Scholar
- Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54(1):25–53. https://doi.org/10.1146/annurev.psych.54.101601.145237 CrossRefPubMedGoogle Scholar
- Saunders JB, Aasland OG, Babor TF, Grant M (1993) Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption—II. Addiction 88(6):791–804. https://doi.org/10.1111/j.1360-0443.1993.tb02093.x CrossRefPubMedGoogle Scholar
- Upadhyay J, Maleki N, Potter J, Elman I, Rudrauf D, Knudsen J, Wallin D, Pendse G, McDonald L, Griffin M, Anderson J, Nutile L, Renshaw P, Weiss R, Becerra L, Borsook D (2010) Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain 133(7):2098–2114. https://doi.org/10.1093/brain/awq138 CrossRefPubMedPubMedCentralGoogle Scholar
- Volkow ND, Wang G-J, Fowler JS, Tomasi D (2012) Addiction circuitry in the human brain. Annu Rev Pharmacol Toxicol 52(1):321–336. https://doi.org/10.1146/annurev-pharmtox-010611-134625 CrossRefPubMedGoogle Scholar
- Zhang X, Zhu X, Wang X, Zhu X, Zhong M, Yi J, Rao H, Yao S (2014) First-episode medication-naive major depressive disorder is associated with altered resting brain function in the affective network. PLoS One 9(1):e85241. https://doi.org/10.1371/journal.pone.0085241 CrossRefPubMedPubMedCentralGoogle Scholar
- Zou QH, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, Wang YF, Zang YF (2008) An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 172(1):137–141. https://doi.org/10.1016/j.jneumeth.2008.04.012 CrossRefPubMedPubMedCentralGoogle Scholar