Patients with Methamphetamine Use Disorder Show Highly Utilized Proactive Inhibitory Control and Intact Reactive Inhibitory Control with Long-Term Abstinence

Abstract

Methamphetamine use disorder (MUD) is a chronic brain disorder that involves frequent failures of inhibitory control and relapses into methamphetamine intake. However, it remains unclear whether the impairment of inhibitory control in MUD is proactive, reactive or both. To address this issue, the current study used the conditional stop-signal task to assess proactive and reactive inhibitory control in 35 MUD patients with long-term abstinence and 35 matched healthy controls. The results showed that MUD patients with long-term abstinence had greater preparation costs than healthy controls, but did not differ in performance, implying a less efficient utilization of proactive inhibitory control. In contrast, MUD patients exhibited intact reactive inhibitory control; reactive but not proactive inhibitory control was associated with high sensation seeking in MUD patients with long-term abstinence. These findings suggest that proactive and reactive inhibitory control may be two different important endophenotypes of addiction in MUD patients with long-term abstinence. The current study provides new insight into the uses of proactive and reactive inhibitory control to effectively evaluate and precisely treat MUD patients with long-term abstinence.

Keywords: methamphetamine use disorder; proactive inhibitory control; reactive inhibitory control; sensation seeking.

Figure 1

Illustration of the C-SST design. Both certain and uncertain blocks contained red arrows as the “Stop” signal in 40% of the trials. Note: SSD = the stop-signal delay. The feedback screen shows an example of a Chinese character that means “correct”.

Figure 2

Behavioral results on the C-SST. The black border, gray-filled violin plot and bars represent the HC results, and the red border, pink-filled violin plot and bars represent the MUD results. The circles within each violin plot and bar represent data for individuals datapoints. (A) Violin plots reveal that the preparation cost in the MUD group was significantly slower than that in the HC group (p < 0.01). The upper, middle, and lower dashed lines within each violin plot represent the upper, middle, and lower quartiles, respectively. (B) The grouped bar chart presents the RTs under the four contexts (Certain-Go, Ignore-Go, Uncertain-Go and Fail-to-Stop) for the HC and MUD groups. (C) The grouped bar chart represents the accuracy in the four contexts (Certain, Ignore, Uncertain and Stop) for the HC and MUD groups.

Figure 3

Scatter plots of preparation cost and SSRT with regression lines and 95% CIs in all participants (A), and the HC (B) and the MUD groups (C). Note: CI, confidence interval; r, Pearson correlation coefficient; p values corrected by FDR.

Figure 4

Scatter plots of SSD and total Sensation Seeking Scale scores with regression lines and 95% CIs in all participants (A) and the HC (B) and MUD groups (C). Note: r, Pearson correlation coefficient; p-values corrected by FDR.

Figure 5

Scatter plot of the Disinhibition of Desire subscales of Sensation Seeking Scale and MUD severity with regression lines and 95% CIs in the MUD group. The severity of MUD was measured by DSM-V. Note: r, Pearson correlation coefficient; p values corrected by FDR.