Hippocampus hyperactivity causes spatial confusion in older adults

March 1, 2021
A hyperactive hippocampus may hamper older adults. (Pixabay/B0red)

A hyperactive hippocampus may hamper older adults. (Pixabay/B0red)

A “noisy” or overactive hippocampal region in the brains of people over 60 has been proven to contribute to a decline in their spatial memory as they age, explaining why it can be difficult for older adults to get acquainted in unfamiliar settings like new cities, a novel virtual reality study found.  

Researchers at the German Center for Neurodegenerative Diseases used a behavioral and brain-scanning virtual reality task to examine how physiological changes in the aging brain affect the formation of spatial knowledge. They determined that older brains are unable to balance activity in the hippocampus, which plays a key role in memory and learning, making brain signals too “noisy” and hindering spatial navigation, according to a paper published March 1 in the Journal of Neuroscience.

In order to explore new surroundings, the human brain needs to rapidly generate spatial representations and flexibly retrieve them later. These abilities deteriorate considerably with age, which is why elderly people commonly struggle with the layout of new environments. 

Spatial navigation is one of the first cognitive abilities that declines in old age, Nadine Diersch, a postdoctoral researcher at the center and lead author of the paper, told The Academic Times. And key regions in the brain’s navigation circuit are also some of the first affected by degenerative disorders like Alzheimer’s disease.

“Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas,” the authors said in the paper. “With advancing age, the ability to learn spatial environments deteriorates substantially, but the underlying neural mechanisms are not well understood.”

The researchers designed two experiments using a virtual city environment to test navigation abilities in a wide age range of adults, and then analyze their underlying neural mechanisms using fMRI, or functional magnetic resonance imaging, scanning. The fMRI technique measures brain activity by detecting changes associated with blood flow.

The virtual environment resembled a typical European historic city center consisting of town houses, shops, restaurants and a square-like spatial layout with four interconnected four-way intersections. The first experiment, which was solely behavioral and did not involve fMRI scanning, used a sample of 34 healthy adults with no signs of major cognitive impairment. 

Participants were categorized into two age groups, with the younger cohort ranging from 21-28 years old and the older group ranging from 61-72 years old. The task began with a familiarization phase during which the participants encountered the virtual environment on a laptop screen for the first time. 

Following the introduction phase, the participants were transported to the different intersections in the city and were tasked with pointing in the direction of one of the environment's target landmarks, either the town hall or the church. This measured how well the participants remembered the layout of the city from different locations. Participants repeatedly performed the pointing task and then toured the whole city again in eight segmented phases of the experiment in order to measure learning across time.

The older group spent significantly more time than the younger group in the initial familiarization phase, according to the paper, and over the course of the experiment the older adults did not perform as well or improve as much in remembering the target landmarks as the younger adults. Most of the younger participants learned the spatial layout of the environment very quickly, the authors said, while the older participants differed more widely in their ability to learn it.

The second experiment, which used fMRI scanning, was run with a different group of adults than the first experiment. The 25 younger adults and 32 older adults in the second sample performed a nearly identical virtual reality task. The fMRI scanning started after the same familiarization phase the participants experienced with the virtual city environment.

The behavioral results were largely the same between the two experiments, with the older adults showing lower performance levels and fewer indications of learning. With the fMRI scanning, the researchers found that activity in the anterior portion of the right hippocampus decreased in the brains of the younger adults during the experiment, but the same pattern was not found in older adults.

This finding suggests that hippocampal activity reflected the amount of spatial knowledge that was acquired by the younger group as they moved through the task. Previous studies of young people have shown that engagement of the retrosplenial cortex and the parieto-occipital sulcus regions of the brain, together with the hippocampus, changes over the course of learning, according to the paper. 

In the current study, brain activity in these regions among the younger adults all changed dynamically as they learned. Brain activity in these same regions among the older adults was not impacted by the amount of knowledge they acquired during the task, and activity in their hippocampus did not decrease, but instead stayed hyperactive.  

This increased hippocampal excitability in elderly people might specifically be impairing the formation of their spatial knowledge, and the authors said their findings add to a growing body of evidence associating hyperactivity in the hippocampus with memory impairments in aging.

Diersch explained that important brain functions like memory or spatial knowledge formation involve communication between multiple regions of the brain, and within each region there are circuits at the cellular level that are either inhibiting brain activity or enhancing it as the brain completes that function. 

The study’s findings indicate that the balance between inhibition and enhancement appears to be off in the hippocampus of aging adults, which may explain some of their cognitive declines. Diersch referred to a hyperactive hippocampus as “noisy” activity that shows that the signal processing and performance in aging brains has changed. A treatment option for improving memory performance in aging adults may be the reduction of hippocampal activity, she noted.

While in the study the older adults as a group performed worse on the task, their individual results varied. There were some older participants who learned as quickly as the younger adults, which Diersch suggested would be an interesting area to explore in follow-up studies.

Another next step for this research is testing it in more realistic settings. Diersch is currently working on a smartphone app that will be able to measure the spatial knowledge formation and exploration behavior of people in the real world. 

The study, “Increased hippocampal excitability and altered learning dynamics mediate cognitive mapping deficits in human aging,” was published March 1 in the Journal of Neuroscience. Nadine Diersch, of the German Center for Neurodegenerative Diseases, was the lead author. Jose Valdes-Herrera, of the German Center for Neurodegenerative Diseases, and Claus Tempelmann and Thomas Wolbers, both of the Otto von Guericke University Magdeburg in Germany, all served as co-authors.

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