Brain scans reveal a crucial difference between younger and older adults

New findings may lead to novel drugs for memory loss.

by Caroline Tien
maze, memory
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From the moment we’re born until the moment we die, we’re tasked with navigating the world.

But does our ability to create accurate mental maps decline with age? A study published Monday in the Journal of Neuroscience suggests aging impairs not only our ability to physically move but also our sense of place.

What's new — The study suggests older adults tend to have more difficulty navigating new environments than twenty-somethings and exhibit corresponding aberrations in activity in two regions of the brain, the anterior hippocampus and the retrosplenial cortex/parieto-occipital sulcus (RSC/POS).

Both the hippocampus and the RSC/POS are known to be involved with the development of spatial memory — the psychological mechanism that enables us to find our way.

Nadine Diersch, the study’s corresponding author and a post-doctoral researcher at the German Center for Neurodegenerative Diseases, tells Inverse that spatial navigation deficits are one of the first symptoms of age-related cognitive decline.

Brain scans revealed hippocampal activity decreases and activity in other navigational areas increases — in the brains of younger study participants. This was not seen in older brains.

Diersch et al., JNeurosci 2021

Changes “in the ability to orient in spatial environments happen very early [in the aging process] and, interestingly, they might give us insights into the progression from healthy to pathological aging because brain regions that are important for spatial navigation are among the first to show signs of Alzheimer's disease-related neuropathology,” Diersch says.

The hippocampus was of particular interest to Diersch and her co-authors because it is thought to play a particularly big role in the generation of “spatial representations” — our sense of where we are in relation to the objects around us.

How they did it — The researchers recruited 17 younger men and women with an average age of 24 and 17 older men and women with an average age of 66 to participate in a behavioral experiment that involved immersion in a virtual-reality environment.

The virtual-reality environment (VE) was modeled on the center of the historic German city of Tübingen and featured shops, houses, restaurants, four four-way intersections, a church, and a town hall. None of the participants had ever been to Tübingen before.

Once they familiarized themselves with the layout of the VE, the participants alternated between taking brief, guided tours and completing a seemingly simple task: pinpointing the direction of either the church or the town hall from one of the intersections. Virtual fog also rolled in, obstructing the view, so navigation was based on their knowledge of their surroundings alone. They repeated the task 96 times — thrice for every possible combination of intersections, directions, and locations.

Subsequently, an entirely different set of younger and older men and women were asked to complete the task 64 times, twice for every possible combination of intersections, directions, and locations, during fMRI brain scanning.

What they discovered — Data analysis revealed a strong correlation between:

  • Youth
  • Baseline performance
  • The capacity for improvement

Older adults were less likely to correctly identify the approximate location of the church or town hall than the younger adults. This trend was not apparent across the board, however.

“While most of our older adults performed worse on the task, their individual results varied quite a bit. There were indeed some older participants who learned as quickly as the younger adults,” Diersch says.

The fMRI scans supported the results of the analysis, revealing concrete differences in patterns of neural activity between members of the two age groups. Specifically, younger adults, on average, exhibited decreasing activity in the hippocampus and increasing activity in the RSC/POS. The same activity levels were not seen in the brains of older adults.

Why this matters — The study provides a novel explanation for age-related spatial navigation deficits: excessive hippocampal activity.

While the exact nature of the link is still a mystery, the researchers theorize hippocampal hyperactivity may interfere with “signal transfer between brain regions,” Diersch says. These findings could potentially inform the development of new drugs for age-related memory loss, which affects 11.7 percent of American adults over the age of 65, according to the Centers for Disease Control and Prevention.

“If going to new places poses too much of a challenge for older adults because they risk getting lost and getting confused, they might consequently avoid such situations, which might restrict their daily life quite a bit,” Diersch says.

“If we find ways that they can do better in such situations without getting overwhelmed, then their quality of life will be improved.”

What's next — The study may inspire further research on the medical applications of drugs that target hippocampal hyperactivity, such as anti-epileptic drugs. These drugs have already been shown to “improve memory performance in amnesic patients,” Diersch says.

The researchers also want to figure out the cause of the discrepancy in performance between some of the older adults.

Determining “why exactly some older adults seem to maintain their performance so well would be another interesting avenue for follow-up studies to see how much they differ from other individuals [in terms of] lifestyle factors, etcetera,” Diersch says.

Abstract: Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment. We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex/parieto-occipital sulcus and anterior hippocampus did not change systematically as a function learning in older compared to younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain’s navigation system, highlighting the critical role of the hippocampus.
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