The widespread use of opioids such as heroin, morphine, fentanyl, and oxycodone has proven to be a complex and persistent predicament for millions of people around the world. Globally, sixteen million people meet the criteria for opioid use disorder (OUD), which is characterized by sustained opioid use that causes clinically salient distress or impairment. In the United States, where OUD contributes to more than forty-seven thousand deaths each year, concerns surrounding addiction and overdose have fueled widespread fears of an “opioid epidemic.” Amidst this backdrop, where insight into the mechanisms underlying substance use disorders seems more critical than ever, researchers at the Yale School of Medicine have identified neural flexibility as a key factor that may be tied to the cognitive impairments commonly observed in individuals with OUD.
The way that different regions of the brain interact with each other is incredibly complicated, but there are certain activation patterns that your brain recurrently engages in. In a study published in JAMA Network Open, neuroscience PhD student Jean Ye identifies these patterns as discrete “brain states.” To various degrees, these states are activated during periods of rest, movie-watching, and exposure to opioid-related stimuli (for example, a needle or a bottle of pills). Using functional magnetic resonance imaging, researchers compared brain activity between people with and without OUD to measure how participants engaged several recurring brain states over time. From there, researchers calculated a metric called state engagement variability, which quantifies participants’ neural flexibility during these conditions. In other words, researchers sought to measure how flexibly participants’ brains could adjust their engagement in different brain activation patterns. Participants were also asked to complete a specific task intended to measure cognitive control, which is one’s ability to direct attention and adjust focus accordingly for different tasks.
Through statistical analysis accounting for many variables, Ye and the researchers identified potential associations between cognitive control and neural flexibility in individuals with OUD. Their analysis showed that—compared to healthy individuals—those with OUD consistently experienced lower variability in their engagement of the recurring brain states investigated in this study, suggesting that it is harder for their brains to adjust accordingly in the face of changing situational demands. According to Ye, this has very real implications, even beyond a clinical research setting, for those who struggle with substance use.
“Individuals with opioid use disorder may have more difficulty disengaging from information related to opioids once they are presented with that information,” Ye said. For example, after observing a bottle of pills on the counter as they brush their teeth, a person with OUD may find it especially challenging to get the thought of opioids out of their head, even once they have left the bathroom. In turn, this image of opioids “stuck in their brain” would likely make it extremely difficult to resist cravings to use the drugs.
The study also revealed that lower neural flexibility during rest periods (following exposure to opioid-associated stimuli) was related to worse cognitive control. This finding suggests an association between reduced neural variability and difficulties in mental functioning and behavior. The results suggest that cultivating a person’s ability to switch between different activation patterns may be an important goal to focus on in treating the cognitive effects of OUD.
These new findings are especially important considering their specificity to opioid use disorder. “With this population, there isn’t much work done looking into [brain] dynamics and flexibility,” Ye said. Although past research had investigated the relationship between cognitive effects and neural flexibility in those with depression and anxiety, little work has questioned this link in those with substance use disorders. However, as opioid use continues to devastate communities across the US and around the world, new research in this field offers an encouraging step forward—bringing renewed hope at a time when it’s needed most.