Neurons in the Human Substantia Nigra Respond to Cognitive Boundaries and Predict Memory

Abstract Segmenting mnemonic episodes from continuous experience is a key aspect of human episodic memory. The brain constantly forms predictions about what will happen next based on previous experience and knowledge, and prediction errors are thought to signal when a new event begins (cognitive boundaries). Dopamine has been closely linked to prediction error signals, yet it remains unknown how human midbrain neurons are modulated by cognitive boundaries and how their responses influence memory. To address these questions, we recorded activity of individual neurons in the human substantia nigra, a critical brain structure for dopamine production and regulation, while participants undergoing deep brain stimulation surgery watched a series of clips embedded with cognitive boundaries and performed a recognition memory task. We found that neural activity in the substantia nigra was robustly modulated by cognitive boundaries during clip viewing. Moreover, a subset of these boundary-responsive neurons also differentiated novel from familiar images during recognition, and their firing rates were indicative of participants’ memory success. These findings reveal that neurons in the human substantia nigra carry boundary- and novelty-related signals consistent with prediction error mechanisms that influence the encoding and retrieval of episodic memories.