Toward biomarkers of the addicted human brain: Using neuroimaging to predict relapse and sustained abstinence in substance use disorder

Abstract

The ability to predict relapse is a major goal of drug addiction research. Clinical and diagnostic measures are useful in this regard, but these measures do not fully and consistently identify who will relapse and who will remain abstinent. Neuroimaging approaches have the potential to complement these standard clinical measures to optimize relapse prediction. The goal of this review was to survey the existing drug addiction literature that either used a baseline functional or structural neuroimaging phenotype to longitudinally predict a clinical outcome, or that examined test-retest of a neuroimaging phenotype during a course of abstinence or treatment. Results broadly suggested that, relative to individuals who sustained abstinence, individuals who relapsed had (1) enhanced activation to drug-related cues and rewards, but reduced activation to non-drug-related cues and rewards, in multiple corticolimbic and corticostriatal brain regions; (2) weakened functional connectivity of these same corticolimbic and corticostriatal regions; and (3) reduced gray and white matter volume and connectivity in prefrontal regions. Thus, beyond these regions showing baseline group differences, reviewed evidence indicates that function and structure of these regions can prospectively predict - and normalization of these regions can longitudinally track - important clinical outcomes including relapse and adherence to treatment. Future clinical studies can leverage this information to develop novel treatment strategies, and to tailor scarce therapeutic resources toward individuals most susceptible to relapse.

Keywords: Clinical outcome; Drug addiction; Functional magnetic resonance imaging; Longitudinal designs; Neuroimaging; Relapse; Voxel-based morphometry.

Figure 1

Representative functional task studies. (A) In alcohol-addicted individuals who completed a cue-reactivity task, fMRI activation in ventral striatum during viewing of alcohol versus neutral pictures predicted a shorter time to relapse. (B) In cocaine-addicted individuals who completed a color-word Stroop task, fMRI activation during interference in the dorsolateral prefrontal cortex predicted the number of weeks in treatment. (C) In cocaine-addicted individuals who completed a monetary incentive delay task, higher fMRI activation in the midbrain was seen post-treatment compared with pre-treatment, and predicted the days abstinent from cocaine. (D) In methamphetamine-addicted individuals who completed a risky-decision making task, fMRI activation in the insula during risky (versus safe) decisions predicted relapse with greater sensitivity and specificity than standard clinical variables. (A) and (B) are adapted from (Reinhard et al., 2015) and (Brewer et al., 2008), respectively, both with permission from Elsevier; (C) and (D) are adapted from (Balodis et al., 2016) and (Gowin et al., 2014), respectively, both with permission from Nature Publishing Group.

Figure 2

Representative functional resting-state studies. (A) In cocaine-addicted individuals, relapse was associated with reduced fMRI connectivity between the left corticomedial amygdala and ventromedial PFC/rostral ACC, but increased fMRI connectivity between the basolateral amygdala and visual processing regions (lingual gyrus/cuneus). (B) In a study using arterial spin labeling, marijuana users at baseline had reduced cerebral blood in the dorsomedial PFC at baseline but not at 4-week follow-up. (A) is adapted from (McHugh et al., 2014), under the Creative Commons Attribution License; (B) is adapted from (Jacobus et al., 2012), with permission from Springer.

Figure 3

Representative structural studies. (A) In methamphetamine-addicted individuals, gray matter volume increased in multiple cortical regions, but decreased in the cerebellum, after one month of abstinence compared with baseline. (B) In cocaine-addicted individuals, abstinence positively correlated with fractional anisotropy (FA) values in the frontal and parietal lobes, and in the body of corpus collosum. (A) is adapted from (Morales et al., 2012), with permission from Elsevier; (B) is adapted from (Xu et al., 2010), with permission from Nature Publishing Group.

Figure 4

Conclusions derived from this review that can inform hypotheses in future work. Relapse was generally associated with enhanced activation to drug-related cues and rewards, reduced activation to non-drug-related cues and rewards, and weakened functional connectivity in corticolimbic and corticostriatal brain regions. Relapse was also generally associated with reduced prefrontal gray and white matter volume and integrity.