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Advanced Neurology Neuroimaging regarding spatial navigation in AD

4.2. Spatial navigation impairment and reduced grid position representation in the navigation system formed
cell-like representations by grid cells and place cells [126] . Carriers of the AD risk gene
Grid cells have unique hexagonal grid-like firing patterns have a more significant decline in the ability to navigate in
and play crucial roles in the process of spatial navigation. the center of the virtual environment than at the border,
Since the discovery in the rat brain by Hafting et al. in 2005, which may be explained by the reason that navigation in
the central area lacks environmental cues that rely more on
the existence of grid cells has been successively confirmed the path integration function of grid cells [127] . Pertinently,
in bats, monkeys, and other animals [25,120] . Grid cells can the increased activation of the hippocampus in risk gene
receive electrical signals from a variety of neuronal cells carriers may serve as a compensatory mechanism for
involved in spatial navigation and are the primary source spatial memory impairment.
of information input to hippocampal place cells [121] . Tau
pathology of AD occurs first in the entorhinal cortex, Phase precession has been widely observed in
the medial part of which contains grid cells. Therefore, hippocampal place cells and entorhinal grid cells in
research that focuses on grid cells in the human brain is of navigating rodents [32,128] . Focal dorsal hippocampal Nav1.1
great value for a better understanding of the neural basis knockdown altered the temporal coding properties of place
underlying spatial navigation impairment in AD. cells, such as theta phase precession, which subsequently
degraded the spatial accuracy of rats [129] . A recent study
The process of reading self-motion information and also provided evidence for spatial phase precession in the
integrating the information of each spatial location human hippocampus and entorhinal cortex during virtual
to obtain the path to the target position is called path navigation, which exhibited features similar to those
integration, which is an automatic and continuous update observed in rodents . Thus, we speculate that degradation
[34]
process during navigation. Grid cells can form stable in the phase precession of grid cells might also contribute
grid graphs, and their path integration function does not to spatial dysfunction in AD patients, which deserves to be
depend on environmental landmarks but is instead based further validated.
on ontology motion cues [122] . Various other cells that are
involved in neural circuits for spatial navigation also have Emerging evidence has suggested the crucial role of
typical firing patterns. Border cells fire significantly when grid cells in spatial navigation, and the application of fMRI
animals approach geometric boundaries [123] ; moreover, the in grid cell research has provided a novel entry point and
firing rate of speed cells increases proportionally with the opened a new avenue for the study of neural mechanisms
movement speed of the animal to provide instantaneous underpinning spatial navigation impairments in AD
speed information . In addition, the firing of head patients. However, due to the complexity of the relevant
[27]
direction cells is related to the direction of the animal data collection and analysis processes, many issues, such
relative to landmarks in the environment [124] . These cells as how grid cells encode three-dimensional (3D) spaces
transmit distance and orientation information to grid cells, and large-scale complex environments in preclinical and
which are integrated into the grid map to provide spatial prodromal AD patients, remain to be further explored.
information, including the position in the environment 5. Nonpharmacological interventions
and distances from starting and ending points, and are for cognitive and spatial navigation
continuously updating location information based on
action cues . impairment
[18]
Fu et al. found that the reduction in grid-cell activation 5.1. Virtual reality (VR)-based training program
in aged mice was accompanied by the occurrence of Due to the high social burden of AD coupled with the lack
spatial memory deficits, and the authors inferred that of effective treatment, new approaches targeting cognitive
pathological changes originating from the entorhinal and spatial navigation impairment are being sought.
cortex may cause grid-cell dysfunction and lead to spatial VR is defined as a technology that digitally provides a
navigation impairment in AD patients [117] . The signals of changeable 3D environment in which people can interact
grid cells have been successfully detected by fMRI, which with different sensory inputs. VR can be immersive or
has greatly facilitated studies of grid cells in humans . nonimmersive, and the former allows for a sense of presence
[24]
Kunz et al. found that young adults with APOE ε4 exhibited in the environment [130] . VR has been widely recognized
reduced grid-cell activation stability and reduced ability as a promising technique that can improve treatment
to navigate in virtual scenes [125] . These results support outcomes in patients with neurocognitive disorders, such
the hypothesis that impaired grid-cell function is related as AD. Oliveira et al. observed an improvement in overall
to spatial disorientation. Bates et al. believed that spatial cognitive function in patients with AD after VR-based
navigation obstacles were mainly caused by the inaccurate cognitive stimulation, with an effect size corresponding to

Volume 1 Issue 2 (2022) 8 https://doi.org/10.36922/an.v1i2.145