Semantic Representational Strength in the Precuneus and Lateral ATL Predicts Successful Factual Learning.

Learning novel facts is central to modern life. While cortical regions involved in this process have been identified, the neural substrates underlying successful knowledge acquisition have remained elusive. In this fMRI study, we presented human participants (N=29; 7, male) with a naturalistic learning task where 120 fictitious encyclopaedic facts relating to people or places drawn from three imaginary civilisations. We then compared items that were subsequently recalled to those that were forgotten on a memory test that targeting associative learning, administered on average a day and a half later. To complement univariate analysis, multivariate pattern analysis was used to identify regions sensitive to semantic content during encoding, identifying medial precuneus, left angular gyrus (AG), intraparietal sulcus (IPS), ventral occipitotemporal cortex (VOTC), and the lateral anterior temporal lobes (latATL) bilaterally. Within these regions, the strength of informational content within the precuneus and left latATL predicted subsequent retrieval. In contrast, planned analyses did not find univariate differences between remembered and forgotten facts. Targeted follow-up ROI analysis indicated a possible role of response magnitude in left inferior frontal gyrus and no univariate or multivariate effects within medial temporal lobe structures. Collectively, these results support a model of fact learning predominantly driven by the richness of representations within semantic systems that is partially distinct from episodic learning mechanisms.Significance Statement The ability to acquire factual knowledge is central to education, work, and daily life, yet the neural mechanisms that support successful fact learning remain unknown. This study shows that successful learning of new facts is predicted not by how much the brain activates, but by the quality of semantic representation in high-level cortical regions, including the precuneus and anterior temporal lobe. These findings reveal a cortical route for factual learning that is distinct from traditional episodic memory mechanisms and emphasise the importance of conceptual integration with prior knowledge. This work advances our understanding of how the brain supports real-world learning and provides a novel framework for studying long-term knowledge acquisition.