Uncovering a role for the dorsal hippocampal commissure in episodic memory

Abstract

32The dorsal hippocampal commissure (DHC) is a white matter tract that provides inter-hemispheric 33 connections between temporal lobe brain regions. Despite the importance of these regions for 34 learning and memory, there is scant evidence of a role for the DHC in successful memory performance. 35 We used diffusion-weighted MRI (DW-MRI) and white matter tractography to reconstruct the DHC 36 across both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings 37 demonstrate close consistency between the known anatomy and tract reconstructions of the DHC. 38Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in 39 nonhuman primates. Finally, we derived Diffusion Tensor MRI (DT-MRI) metrics from the DHC in a 40 large sample of human subjects to investigate whether inter-individual variation in DHC 41 microstructure is predictive of memory performance. The mean diffusivity of the DHC was correlated 42 with performance in a standardised episodic memory task; an effect that was not reproduced in a 43 comparison commissure tract -the anterior commissure. These findings highlight a role for the DHC 44 in episodic memory, and our tract reconstruction approach has the potential to generate further novel 45 insights into the role of this previously understudied white matter tract in both health and disease. 46 47 48 The two hemispheres of the brain are connected by commissural fiber systems that include the corpus 50 callosum, anterior commissure (AC), posterior commissure, ventral hippocampal commissure (VHC), 51 and dorsal hippocampal commissure (DHC) (Demeter et al. 1985). The DHC (alternatively the 'dorsal 52 psaltarium') provides inter-hemispheric connections between functionally-related structures in the 53 medial temporal lobes (MTL), including the presubiculum, entorhinal and parahippocampal cortex 54 (Demeter et al. 1985(Demeter et al. , 1990Gloor et al. 1993). Given that these regions play a key role in successful 55 learning and memory (Zola-Morgan et al. 1989; Squire and Zola-Morgan 1991; Aggleton and Brown 56 1999; Aggleton 2012), their ability to communicate effectively with contralateral homologous regions 57 via the DHC may also be important for performance in these cognitive domains. 58There have, however, been few studies of the function of the DHC, potentially due to 59 misunderstanding around the cross-species anatomy of the DHC, as distinct from other local fiber 60 populations such as the VHC, fornix, and corpus callosum (Demeter et al. 1985;Raslau et al. 2015; 61 Tubbs et al. 2015). In rodents, the VHC supports dense inter-hemispheric connections between the 62 hippocampi, which originate throughout the long-axis of the hippocampus; in nonhuman primates, 63 VHC connections are reduced so that only the uncal and genual subdivisions of the hippocampal 64 formation are connected to those in the contralateral hemisphere (Demeter et al. 1985; Gloor et al. 65 1993). By contrast, the DHC remains a substantial tract in nonhuman prima...