Autobiographical Memory in Opioid Use Disorder

In this study, we propose to characterize possible OUD-related dysfunction in AM. We will further examine the impact of a cognitive training intervention (Memory Flexibility Training [MemFlex]) on AM and drug use outcomes and explore the underlying brain and physiological mechanisms.

Autobiographical memory and OUD:

AMs are episodic memories of one's own life. Under healthy circumstances, AMs are not simple facts (frozen in time) but are influenced by the current context to help maintain a positive sense-of-self and motivate adaptive behaviors. That is, individuals flexibly focus AM to retrieve details that help with current goals, or they adjust AM-related emotions to assist in current regulation of emotion. Patients across psychiatric disorders often have difficulty recalling specific AMs (i.e., those of a single brief event) and show dysfunction in the vividness and emotionality of AMs. The few studies on AM in OUD indicate these individuals recall fewer specific AMs have easier access to neutral AMs, and less positive AMs.

Memory Flexibility Training:

MemFlex employs cognitive training exercises in self-led sessions to improve 1) switching between specific and general AMs, 2) access to positive AMs, and 3) vividness of positive AMs. In trials for depression and posttraumatic stress, MemFlex has improved symptoms and AM recall but MemFlex has not been tested for OUD. Previous research has shown that chronic drug use can lead to increased dopaminergic brain response to drug reward cues/reminders (which are learned over time) and reduced dopaminergic brain response to receiving both drug and non-drug rewards (in-the-moment). This can create reward inflexibility, in which drug rewards drive motivation while non-drug rewards contribute relatively little. Further, work in our lab and others has shown OUD is associated with cognitive inflexibility, which is an impaired ability to switch between mental tasks when contexts change and may impair decision-making. Inflexibility in the reward and cognitive systems may leave individuals 'stuck' choosing drug rewards to the exclusion of other rewards (e.g., relationships, work). We propose that MemFlex, by improving access to non-drug reward-related AMs and the ability to switch between types of AMs, will help patients with OUD use AM to regulate emotions and pursue healthier rewards.

Neurobiological Foundation of Flexibility:

The brain's prefrontal cortex (PFC) is critical to successful cognitive flexibility and reward function. It is also implicated in AM deficits and is impaired in people with OUD. As such, we will use PFC activity during AM and reward flexibility task may explain the neural foundations of related deficits. Previous research has also shown that physiological arousal, as measured by heart rate variability (HRV), contributes to cognitive flexibility and correlates with PFC and subcortical brain areas that support flexibility. Therefore, HRV (i.e., the time fluctuation between heartbeats) may contribute to deficits in AM and reward flexibility and be a marker of MemFlex treatment success.