Causal neural mechanisms for decision making : putting rules into context

Abstract

Episodic memory, an important cognitive process in humans, relies on both contextual and temporal information to recall sequences of events accurately. While nonhuman animals are capable of understanding rules based on context and have shown capability in learning temporal sequences, the ability to flexibly shift between these types of information has yet to be demonstrated. This thesis aimed to explore the cognitive mechanisms behind adapting memory sequences to changing contexts in three species. Following work in Lister hooded rats, the study was extended to New world (Common marmosets) and Old world monkeys (Rhesus macaques) to assess each species’ proficiency in learning context-guided sequences. In addition, a noninvasive technique called transcranial ultrasound stimulation (TUS) was employed with the macaques to investigate potential underlying neurobiological pathways. The task design, consistent across all three species, involved learning visual object sequences (e.g., A-B or C-D) where the correct choice was contingent on one of two background contexts (e.g., blue or yellow). Results showed that rats and marmosets were proficient in learning sequences that remained constrained to a singular context but faced challenges with sequences involving a mid-trial contextual shift. Conversely, the macaques quickly mastered both fixed and context-switching sequences, facilitating further investigation into potential neurobiological mechanisms using TUS. Prior research suggests a possible role for the prefrontal-hippocampal circuitry in context-dependent learning, prompting us to apply targeted modulation to the hippocampus and prefrontal cortex separately. Notably, TUS of the anterior hippocampus enhanced performance during the initial stages of learning. In contrast, TUS of the prefrontal cortex enhanced performance in the later phases, particularly in trials that required a context shift mid-trial. Overall, this research highlights the evolutionary foundation of flexible learning and offers insights into neural modulation in primate cognition, particularly in how the brain adapts dynamically to contextual shifts when guiding memory sequences