| Abstract: | 主計處在民國 88 年調查發現有 150 萬台灣人是檳榔嚼食者，嚼食者平均每天大約 嚼 14 到 23 顆檳榔。在此研究中，我們檢驗慣嚼檳榔者的線索誘發之渴求以及可能的大 腦結構變異。過去研究發現檳榔鹼(檳榔的主要成分)會對皮質與皮質下的腦區有廣泛的 影響。但是目前仍不清楚嚼食檳榔對成癮相關腦區之影響(例如杏仁核-紋狀系統與前額 葉控制系統)。此研究問題十分重要，因為這兩個系統的平衡對於物質使用十分重要 (Heatherton & Wagner, 2011; Noël, Brevers, & Bechara, 2013)。當衝動高過前額葉控制，或 者前額葉控制系統損傷，物質使用會增加。另一方面，當前額葉控制系統高過衝動，或 者衝動微弱時，物質使用會減少。 在實驗一，我們採取線索反應典範以及作業為基功能性磁振造影來檢驗檳榔線索所 誘發的渴求。在實驗二，我們採用擴散性磁振造影與靜息態功能性磁振造影來檢驗檳榔 嚼食者與成癮相關的大腦結構(例如杏仁核-紋狀系統與前額葉控制系統)。此外，我們使 用停止信號作業以及單一類別內隱態度作業來檢驗嚼食者的抑制控制與對檳榔的內隱 態度。我們認為抑制控制與內隱態度會與擴散性磁振造影與靜息態功能性磁振造影的結 果呈現正相關。在停止信號作業中，參與者要進行形狀再認作業，但是偶爾(25%)會有 聽覺訊號(停止信號)要參與者不對形狀反應。有較佳抑制能力的參與者比較可以抑制按 鍵之反應。也就是這些參與者需要處理停止信號與抑制按鍵反義的時間較短，也就是有 較短的停止信號反應時間。反之，較長的停止信號反應時間顯示較差的抑制控制能力。 此較差的抑制能力可能主要發生在成癮者。單一類別內隱態度作業主要測量對客體的內 隱態度。此作業中，參與者要將刺激物(文字或圖)盡快且正確地分類到”愉悅”或”不愉悅” 的標籤。如果參與者較快將檳榔分類到愉悅，表示其內隱態度偏好檳榔。 此研究讓我們有機會第一次看到慣嚼檳榔者的大腦狀態。這些腦造影給了研究者與 臨床工作者重要線索以發展對慣嚼者有效的戒斷治療。這也是第一次應用擴散性磁振造 影與靜息態功能性磁振造影在嚼食檳榔者。這些造影提供了十分優良的結構與功能上的 大腦改變訊息。
In two experiments, we aim to examine the cue-elicited craving and possible brain structural abnormalities in the betel nut chewers. Previous studies have shown that arecoline (the primary ingredient in betel nut) can have widespread effect in cortical and subcortical areas. However, it is still unclear whether habitual betel nut chewing affects brain areas involving addiction (e.g., the amygdala-striatal system and prefrontal control system). This question is important because the balance of these two systems is considered to be critical to substance use (Heatherton & Wagner, 2011; Noël, Brevers, & Bechara, 2013). When impulses overwhelm prefrontal control or when prefrontal control is impaired, substance use is increased. On the other hand, when prefrontal control overwhelms impulses or when impulses are weak, substance use may be decreased. In Experiment 1, we will adopt the cue-reactivity paradigm and task-based functional MRI (fMRI) to evaluate craving induced by the betel nut cues. In Experiment 2, we will adopt the diffusion MRI (dMRI) and resting-state fMRI to evaluate betel nut chewers’ brain structure involving addiction (e.g., amygdala-striatum system and prefrontal control system). In addition to brain imaging, we use stop-signal task and single-category implicit attitude task (SC-IAT) to assess betel nut chewers’ inhibitory control and implicit attitude toward betel nut, respectively. The behavioral performances of stop-signal task and SC-IAT are expected to correlate to the brain structures revealed by dMRI and resting-state fMRI. In the stop signal task, participants perform a shape recognition task, but in some trials, an auditory warning (a stop signal) instructs them to withhold their response. Individuals with better inhibitory control are likely to inhibit a prepotent response on stop trials. The stop-signal reaction time (SSRT) was primarily analyzed to assess the inhibitory control ability. It reflects the time required to process stop signals and to withhold responses; therefore, longer SSRT indicates a worse inhibitory control. The deficits in SSRT have been pronounced in the dependent group. The SC-IAT has been developed to measure the implicit attitudes to an attitude object. Participants are instructed to categorize the stimulus (words and pictures) at the center of the display under the categories of “pleasant” and “unpleasant” as quickly and accurately as possible. Short time to categorize the attitude object (e.g., betel nut) to the “pleasant” label indicate an implicit attitude favoring this attitude object. The current project gives us the first opportunity to “visualize” the chewers’ brains. These brain imaging can provide important insight to the researchers and the clinicians as to develop an effective abstinence treatment for these chewers. This is the first study in the world to validate the application of non-Gaussian dMRI (GQI) and resting-state fMRI in the habitual betel nut’s addictive brains. Together they may provide better structural and functional information of the brain changes. |
