Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multimodal imaging investigation.

Young adult APOE-ε4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (one half of whom were APOE-ε4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB)-which links the pDMN and the medial temporal lobe-was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity and fractional anisotropy) were then extracted from these tract delineations. APOE-ε4 carriers had lower mean diffusivity and higher fractional anisotropy relative to noncarriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus). Furthermore, PHCB microstructure was selectively associated with pDMN (and medial temporal lobe) activity during a scene discrimination task known to be sensitive to Alzheimer's disease. These findings are consistent with a lifespan view of Alzheimer's disease risk, where early-life, connectivity-related changes in specific, vulnerable "hubs" (e.g., pDMN) lead to increased neural activity. Critically, such changes may reflect reduced network efficiency/flexibility in APOE-ε4 carriers, which in itself may portend a faster decline in connectivity over the lifespan and ultimately trigger early amyloid-ß deposition in later life.

On the (a)symmetry between the perception of time and space in large-scale environments.

Cross-dimensional interference between spatial and temporal processing is well documented in humans, but the direction of these interactions remains unclear. The theory of metaphoric structuring states that space is the dominant concept influencing time perception, whereas time has little effect upon the perception of space. In contrast, theories proposing a common neuronal mechanism representing magnitudes argue for a symmetric interaction between space and time perception. Here, we investigated space-time interactions in realistic, large-scale virtual environments. Our results demonstrate a symmetric relationship between the perception of temporal intervals in the supra-second range and room size (experiment 1), but an asymmetric relationship between the perception of travel time and traveled distance (experiment 2). While the perception of time was influenced by the size of virtual rooms and by the distance traveled within these rooms, time itself affected only the perception of room size, but had no influence on the perception of traveled distance. These results are discussed in the context of recent evidence from rodent studies suggesting that subsets of hippocampal place and entorhinal grid cells can simultaneously code for space and time, providing a potential neuronal basis for the interactions between these domains.

The Human Retrosplenial Cortex and Thalamus Code Head Direction in a Global Reference Frame.

UNLABELLED: Spatial navigation is a multisensory process involving integration of visual and body-based cues. In rodents, head direction (HD) cells, which are most abundant in the thalamus, integrate these cues to code facing direction. Human fMRI studies examining HD coding in virtual environments (VE) have reported effects in retrosplenial complex and (pre-)subiculum, but not the thalamus. Furthermore, HD coding appeared insensitive to global landmarks. These tasks, however, provided only visual cues for orientation, and attending to global landmarks did not benefit task performance. In the present study, participants explored a VE comprising four separate locales, surrounded by four global landmarks. To provide body-based cues, participants wore a head-mounted display so that physical rotations changed facing direction in the VE. During subsequent MRI scanning, subjects saw stationary views of the environment and judged whether their orientation was the same as in the preceding trial. Parameter estimates extracted from retrosplenial cortex and the thalamus revealed significantly reduced BOLD responses when HD was repeated. Moreover, consistent with rodent findings, the signal did not continue to adapt over repetitions of the same HD. These results were supported by a whole-brain analysis showing additional repetition suppression in the precuneus. Together, our findings suggest that: (1) consistent with the rodent literature, the human thalamus may integrate visual and body-based, orientation cues; (2) global reference frame cues can be used to integrate HD across separate individual locales; and (3) immersive training procedures providing full body-based cues may help to elucidate the neural mechanisms supporting spatial navigation. SIGNIFICANCE STATEMENT: In rodents, head direction (HD) cells signal facing direction in the environment via increased firing when the animal assumes a certain orientation. Distinct brain regions, the retrosplenial cortex (RSC) and thalamus, code for visual and vestibular cues of orientation, respectively. Putative HD signals have been observed in human RSC but not the thalamus, potentially because body-based cues were not provided. Here, participants encoded HD in a novel virtual environment while wearing a head-mounted display to provide body-based cues for orientation. In subsequent fMRI scanning, we found evidence of an HD signal in RSC, thalamus, and precuneus. These findings harmonize rodent and human data, and suggest that immersive training procedures provide a viable way to examine the neural basis of navigation.

Dissociable roles of the inferior longitudinal fasciculus and fornix in face and place perception.

We tested a novel hypothesis, generated from representational accounts of medial temporal lobe (MTL) function, that the major white matter tracts converging on perirhinal cortex (PrC) and hippocampus (HC) would be differentially involved in face and scene perception, respectively. Diffusion tensor imaging was applied in healthy participants alongside an odd-one-out paradigm sensitive to PrC and HC lesions in animals and humans. Microstructure of inferior longitudinal fasciculus (ILF, connecting occipital and ventro-anterior temporal lobe, including PrC) and fornix (the main HC input/output pathway) correlated with accuracy on odd-one-out judgements involving faces and scenes, respectively. Similarly, blood oxygen level-dependent (BOLD) response in PrC and HC, elicited during oddity judgements, was correlated with face and scene oddity performance, respectively. We also observed associations between ILF and fornix microstructure and category-selective BOLD response in PrC and HC, respectively. These striking three-way associations highlight functionally dissociable, structurally instantiated MTL neurocognitive networks for complex face and scene perception.