THE NEUROBIOLOGICAL BASIS & MANIPULATION OF MEMORY GENERALIZATION

Anxiety affects 4.4-million children in the United States. Its age of onset is between childhood and adolescence (i.e., peri-adolescence), a period marked by neural changes that impact emotions and memory. Negative overgeneralization – or responding similarly to innocuous events that share features with past aversive experiences – is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) and its connectivity with limbic areas has been considered an important contributor in the modulation of memory generalization. I investigated the activation and functional connectivity of the RE with the medial prefrontal cortex (mPFC), CA1 subfield of the hippocampus, and amygdala, as neurobiological mechanisms of negative overgeneralization in anxious youth. During the Study session, participants were instructed to provide the valence rating of images (e.g., negative). At the Test session, they performed a memory recognition test with repeated (targets), similar (lures), and new (foil) images. Labeling negative relative to neutral lures as “old” (false alarms) was our operational definition of negative overgeneralization. My results demonstrated the elevated activation of the RE for negative relative to neutral false alarmed stimuli (at Study and Test) and increased functional connectivity with the CA1 (at Test only). Further, elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. The functional connectivity between the RE and amygdala, nor did their respective functional coupling with the CA1 display significant changes for negative relative to neutral images that were false alarmed. For the final chapter of my dissertation, I examined the influence of Episodic Specificity Induction (ESI) at encoding, as a means to modulate the precision of memory traces and improve memory discrimination. Prior to the eMST task, participants went through the ESI and a control condition. During the ESI training, they were prompted to recall details about the surroundings, people, and sequence of actions of a short video that was previously presented. I failed to confirm the efficacy of the ESI in improving the discrimination of memories. However, exploratory analyses revealed that increased sequence memory recall, regardless of whether it occurred during the ESI or control condition, improved the discrimination of overlapping memory traces.

Major Professor: Dr. Aaron Mattfeld

Co-Major Professor: Dr. Dana McMakin