Presumed structural and functional neural recovery after long-term abstinence from cocaine in male military veterans

Abstract

Cumulative evidence suggests that cocaine use could alter the structure and function of different brain systems. However, the extent to which the altered brain structure and function possibly recover over time after cocaine abstinence remains less clear. The present study examines 39 male military veterans with different stages of cocaine addiction and long-term abstinence (from 1 year up to 30 years) and evaluates plausible changes in brain structure and function of specific brain regions that sub-serve addictions. These include the striatum that is involved in cocaine reward; the lateral prefrontal cortex (especially the dorsolateral PFC) that plays a major role in inhibitory control; the insula, which has been implicated in craving; and the medial orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) shown to play key roles in foresight and decision-making. The results suggest that there are differences in both brain structure (gray matter volume, GMV) and function between cocaine USERS and CONTROLS, with USERS showing plausible relative strengthening in neural systems for processing reward and craving, and relative weakening in neural systems involved in inhibitory control and decision-making. Examination of possible neural changes after abstinence suggests that presumed recovery occurs mostly in neural systems related to reward, craving, and inhibitory control, but to a lesser extent in neural systems related to decision-making. Given the limitations of the data in terms of a small sample size, as well as the lack of certainty about occasional use in the abstinent group, these results may be considered as preliminary. However, they are compelling in that they suggest that male military veterans cocaine USERS are indefinitely at a higher risk compared to CONTROLS for making lapses in judgment and decision-making leading to possible relapse, if reward salience and craving become more intense. Understanding the neurobiology of long-term cocaine abstinence in vulnerable populations and beyond could help devising better therapeutic strategies that prevent relapse.

Keywords: Abstinence; Cocaine addiction; Functional connectivity; VBM; fMRI.

Figure 1

Example stimuli of A) Cocaine related pictures, and B) natural scenes control pictures used in the present study.

Figure 2

GMV in four key brain regions and its relationship with years of abstinence. A) The right striatum showed higher GMV in USERS than in CONTROLS and ABSTINENCE. There were also difference between USERS and ABS1 (i.e., those who recently quit using cocaine; less than 5 years ago). Years of abstinence inversely predicted the GMV in the right striatum. B) The left insula showed higher GMV in USERS than in CONTROLS. Years of abstinence also inversely predicted the GMV in the left insula. C) The right LFP showed lower GMV in USERS than in CONTROLS and ABSTINENCE. There was also observable difference between USERS and ABS1 (i.e., those who recently quit using cocaine; less than 5 years ago). Years of abstinence positively predicted the GMV in the right LFP. D) The left OFC showed higher GMV in CONTROLS than in USERS and ABSTINENCE. The difference was noticeable also between CONTROLS and ABS3 (i.e., those who quit using cocaine more than 11 years ago). The correlation suggested that there is no significant recovery in this region. In the visualized brain slices, red color illustrates the corresponding brain region. R indicates the right hemisphere. Numbers below the slice indicate the MNI coordinates of the slice. ABC is displayed in sagittal view and D is displayed in axial view.

Figure 3

Brain activation in four key brain regions and relationships with years of abstinence. A) The right striatum showed higher activation in USERS when facing cocaine pictures than when facing control pictures. The activation in this area of USERS was higher than this of CONTROLS and ABSTINENCE, and even higher than this of ABS1 (i.e., those who recently quit using cocaine; less than 5 years ago). Years of abstinence could inversely predict brain activation in the right striatum. B) The left insula showed higher activation in USERS when facing cocaine pictures than when facing control pictures. The activation in this area for USERS is higher than this for CONTROLS. Years of abstinence could also inversely predict brain activation in the left insula. C) The right LFP in USERS showed higher activation when facing cocaine pictures than when facing control pictures. The activation in this area of USERS and ABSTINENCE was higher than in this area of CONTROLS. Years of abstinence could inversely predict brain activation in right LFP. D) The left VMPFC showed higher activation when facing cocaine pictures than when facing control pictures in CONTROLS. The activation in this area of CONTROLS was higher than this of USERS and ABSTINENCE, and even higher than this of ABS3 (i.e., those who quit using cocaine more than 11 years ago). The correlation suggested that there is no recovery for this region. In the visualized brain slices, yellow or green colors illustrate the corresponding brain region. R indicates the right hemisphere. Numbers below the slice indicate the MNI coordinates of the slice. AC are displayed in coronal view, B is displayed in sagittal view, and D is displayed in axial view. R indicates the right hemisphere.

Figure 4

A) Significant connections for the CONTROLS group tested by one sample t tests. Except for the connectivity between the left VMPFC and the right LFP, and the connectivity between the left Insula and the right LFP, all other connections were significant (in red). The mean correlational coefficients are displayed for each significant connection. B) Significant connections for the USERS group tested by one sample t tests. Results suggested that only the connectivity between the left VMPFC and the left Insula is significant. The mean correlational coefficient is displayed for this connection. C) Three connections significantly differed between CONTROLS and USERS, including connections between the left Insula and the right Striatum, the left VMPFC and the right striatum, and the right LFP and right Striatum. T statistics for each significant connection are displayed. D) Two connections were also significantly positively correlated with years of abstinence, including the connections between the right LFP and the right Striatum and between the left Insula and the right Striatum. However, the connection between the left VMPFC and the right striatum did not correlate with years of abstinence. Correlational coefficients are displayed for each significant correlation.