Scientists at Stanford University have discovered that certain brain responses to potential monetary losses can predict the likelihood of relapse in individuals recovering from stimulant addiction. This finding, derived from a detailed analysis involving brain imaging and behavioral tests, offers a new window into understanding and potentially preventing one of the most challenging aspects of addiction treatment: the risk of returning to drug use after treatment. The new research has been published in Biological Psychiatry.
The motivation behind this research lies in the alarming increase in addiction to stimulants like methamphetamine and cocaine. With rising mortality rates due to overdoses and a significant number of people struggling with Stimulant Use Disorder, researchers have been urgently seeking better ways to predict and prevent relapse. Despite advances in treatment methods, relapse rates remain high, underscoring the need for more effective strategies.
“Addiction often involves repeated relapse. For instance, more than half of individuals treated for stimulant use disorder relapse within six months after leaving treatment. Yet, researchers know little about which psychological and neural mechanisms might protect people from relapse. Relevant insights could improve both predicting and treating relapse to stimulant use,” explained doctoral candidate Leili Mortazavi and Professor Brian Knutson, who co-authored the study along with research scientist Kelly H. MacNiven.
The study was conducted over several years and involved a comprehensive approach. Researchers at Stanford University and the Veterans Affairs Palo Alto Health Care System enrolled 79 patients who had been detoxified from stimulant drugs. These patients were a part of residential treatment programs in California. However, after considering factors like head motion during scans and task engagement, the final sample for the study was narrowed down to 68 patients for baseline analysis and 60 for relapse analysis. The study also included 42 healthy control participants for comparison.
Participants underwent a series of tests, including functional Magnetic Resonance Imaging (fMRI), while performing a Monetary Incentive Delay (MID) task. This task involves responding to cues that signal potential monetary gains or losses, thus engaging brain regions associated with reward processing and anticipation. Participants also completed several questionnaires to assess aspects like impulsivity, depression, and decision-making. The researchers closely followed these participants, conducting follow-up interviews at 1, 3, and 6 months post-treatment discharge to track any instances of relapse.
The researchers discovered that patients with diminished activity in a specific part of the brain, known as the anterior insula, during anticipation of significant monetary losses (−$5) were more likely to return to stimulant use. This decreased brain activity was consistently linked with a higher likelihood of relapse. The study showed that this pattern was especially pronounced when participants anticipated large monetary losses, as opposed to smaller losses or gains.
Additionally, the study revealed behavioral correlations. Participants with reduced anterior insula activity responded more slowly to cues indicating large potential losses and reported feeling less negative arousal from these cues. This suggests that their motivational response to avoid negative outcomes was diminished, which might be a crucial factor in understanding why they are more prone to relapse.
“Patients with stimulant use disorder who show greater neural as well as behavioral responses to anticipated losses (e.g., of money) remained drug-free longer after leaving treatment,” Mortazavi and Knutson told PsyPost. “Interestingly, these neural and behavioral makers of loss avoidance did not distinguish patients overall from healthy controls, implying that loss avoidance may specifically confer resilience against relapse. These convergent findings highlight specific targets for predicting and preventing relapse.”
In terms of structural brain features, the researchers found a link between the reduced activity in the anterior insula during loss anticipation and lower structural coherence in a specific brain circuit involving the anterior insula and the nucleus accumbens, a region associated with reward processing. This finding adds another layer to our understanding by connecting functional brain responses with structural brain characteristics.
When the researchers looked at brain responses to potential monetary gains, they did not find a significant difference between patients who relapsed and those who did not. This was true both in the overall activity in the anterior insula and other brain regions associated with reward processing, like the nucleus accumbens. The lack of significant findings here suggests that the brain’s response to potential gains may not play as critical a role in the context of relapse for individuals with Stimulant Use Disorder as the response to potential losses does.
“Previous research implicated anticipation of drug-related gain in relapse, so we thought that anticipation of monetary gains might also be relevant to relapse,” Mortazavi and Knutson explained. “Instead, the current findings implicate neural and behavioral responses to anticipated loss in relapse.”
“Additionally, the evidence converged across different measures including behavior, brain activity, and even brain structure to implicate an integrated circuit involved in loss anticipation and avoidance. Together, these findings imply that the neurobehavioral mechanisms that push people towards problematic drug use may be different from those that keep them away from relapse.”
Despite these significant findings, the study has its limitations. The sample size, while adequate for the study’s aims, limits the generalizability of the findings to the broader population. Additionally, the study primarily involved participants from specific residential treatment programs, which might not represent the entire spectrum of individuals with stimulant addiction. Another important consideration is that the study did not assess some comorbid conditions that might influence addiction and relapse, such as mental health disorders. Furthermore, the study’s design could not conclusively determine whether the observed brain patterns were a cause or a consequence of chronic stimulant use.
“The findings should be replicated and potentially generalized to other addictive disorders (e.g., Alcohol Use Disorder, which we’re currently writing up),” Mortazavi and Knutson told PsyPost. “Blunted loss anticipation might either precede or be modified by drug use, but we found no association with previous use in the current research. In future research, we are excited about exploring how to modify loss anticipation, and testing whether this can reduce relapse.”
Nevertheless, the findings provide an important foundation for future research. By providing a clearer picture of how the brain responds to potential losses, this research opens new avenues for predicting and, potentially, preventing relapse. It suggests that targeted therapies could be developed to strengthen the brain’s response to negative outcomes, which could be particularly beneficial for individuals at higher risk of relapse.
The researchers added: “This exploratory longitudinal research was generously supported by the Neurochoice Initiative of Stanford’s Wu Tsai Neurosciences Institute, and more information about our interdisciplinary efforts to predict and prevent addictive relapse can be found at: https://neurochoice.stanford.edu/.”
The study, “Blunted Neurobehavioral Loss Anticipation Predicts Relapse to Stimulant Drug Use“, was authored by Leili Mortazavi, Kelly H. MacNiven, and Brian Knutson.
