Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging

Abstract

Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets.

Keywords: Addiction; Corticostriatal circuitry; Diffusion tensor imaging; Magnetic resonance imaging; Methamphetamine; Positron emission tomography.

Figure 1. Changes in gray matter during early abstinence from methamphetamine

In methamphetamine-dependent individuals, gray matter increased between the first and fourth weeks of abstinence from methamphetamine (results displayed at a statistical threshold of p < 0.005 uncorrected with a cluster extent > 200 voxels). No changes in gray matter were detected in healthy control participants who underwent two scanning sessions approximately 1 month apart. The left hemisphere is displayed on the left side of the image.

Figure 2. Exposure to escalating methamphetamine causes structural changes in the vervet monkey brain

In the effect size (Cohen’s d) map, positive values (warmer colors) indicate brain regions where gray matter increased in the methamphetamine-exposed group relative to the saline controls; negative values (cooler colors) depict the converse relationship. Methamphetamine exposure produced a significant increase in gray matter in the striatum compared to saline (p < 0.05 corrected for multiple comparisons). The left hemisphere is depicted right side of the image.

Figure 3. Differences in brain function during risky decision-making between methamphetamine-dependent and healthy control participants

The linear relationship between risk levels and activation in the dorsolateral prefrontal cortex (blue) was greater in control group than in the methamphetamine-dependent group; however, the opposite relationship was found in the greater in the ventral striatum (red) (p < 0.05, cluster corrected). Results were controlled for age, sex, smoking status, and marijuana use.

Figure 4. Relationship between prefrontal brain function during risky decision-and resting-state connectivity of the midbrain in methamphetamine-dependence

Connectivity maps show a negative correlation between modulation of activation in right dorsolateral prefrontal cortex during risky decision-making and the connectivity between midbrain seed (shown in blue) and nucleus accumbens, putamen, amygdala, hippocampus, orbitofrontal cortex, anterior cingulate, and superior frontal gyrus in methamphetamine-dependent individuals (p < 0.05, whole-brain cluster corrected). Results controlled for age, sex, smoking status and marijuana use.