Exploring individual differences in amygdala-mediated memory modulation.

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without subjective emotional arousal at the one-day delay, but not at the immediate delay, for previously stimulated objects compared to not stimulated objects. Importantly, we observed a larger variation in performance across this larger sample than our initial sample, including some participants who showed a memory impairment for stimulated objects. Of the explored individual differences, the factor that most accounted for variability in memory modulation was each participant's pre-operative memory performance. Worse memory performance on standardized neuropsychological tests was associated with a stronger susceptibility to memory modulation in a positive or negative direction. Sex differences and the frequency of interictal epileptiform discharges (IEDs) during testing also accounted for some variance in amygdala-mediated memory modulation. Given the potential and challenges of this memory modulation approach, we discuss additional individual and stimulation factors that we hope will differentiate between memory enhancement and impairment to further optimize the potential of amygdala-mediated memory enhancement for therapeutic interventions.