Not everything withers with age

Layer number four of our neocortex keeps growing and growing –with astonishing consequences for our perception.

Professor Esther Kühn with her team. In the background are MRI images showing the human neo-cortex in blue.

I recently asked myself if I still have a healthy brain as I get older. I hold a professorship in a neurology department at the University of Tübingen. Nevertheless, it is difficult for me to judge if a particular brain, including my own, suffers from early neurodegeneration, that is, progressive loss of nerve cells. My new study, however, shows that part of your brain increases in size with age rather than degenerating. The reason it’s so hard to measure early signs of neurodegeneration is because of how complicated it is to measure small structures in our brain.

Modern neuroimaging technology allows us to detect a brain tumor or to identify an epileptic lesion. These abnormalities are several millimeters in size and can be depicted by a magnetic resonance imaging (MRI) scanner, which operates at around 30,000-60,000 times stronger than the natural magnetic field of the Earth. The problem is that human thinking and perception operate at an even smaller scale. Our thinking and perception happens in the neocortex. This outer part of our brain consists of six layers. When you feel touch to your body, layer four of your sensory cortex gets activated. This layer is the width of a grain of sand – much smaller than what MRI scanners at hospitals can usually depict. When you modulate your body sensation, for example by trying to read this text rather than feeling the pain from your bad back, layers five and six of your sensory cortex get activated – which are even smaller than layer four.

A patient is placed in a magnetic resonance imaging (MRI) scanner. The metal ring generates a strong magnetic field, causing hydrogen atoms in the human body to vibrate at different frequencies.

For my study, published in the journal Nature Neuroscience, I had access to a 7 Tesla MRI scanner which offers five times better image resolution than standard MRI
scanners. It makes snapshots of the fine- scale brain networks during perception and thought visible.

Using a 7 Tesla scanner, my team and I investigated the sensory cortex in healthy younger adults (around 25 years old) and healthy older adults (around 65 years old) to better understand brain aging.¹We found that only layers five and six, which modulate body perception, showed signs of age-related degeneration ². Layer four, needed to feel touch to your body, was enlarged in healthy older adults in my study. We also did a comparative study with mice. We found similar results in the older mice, in that they also had a more pronounced layer four than the younger mice. However evidence from our study of mice, which included a third group of very old mice, showed this part of the brain may degenerate in more advanced old age.

A patient lying in an MRI scanner. — The strength of a magnetic field is measured in “Tesla” – named after the famous physicist Nikola Tesla (1856–1943).

Current theories assume our brain gets smaller as we grow older.³ But my team’s findings contradict these theories in part. It is the first evidence that some parts of
the brain get bigger with age in normal older adults. Older adults with a thicker layer four would be expected to be more sensitive to touch and pain, and (due to the reduced deep layers) have difficulties modulating such sensations.

To understand this effect better, we studied a middle-aged patient who was born without one arm. This patient had a smaller layer four. This suggests their brain received fewer impulses in comparison to a person with two arms and therefore developed less mass in layer four. Parts of the brain that are used more develop more synapses, hence more mass. Rather than systematically degenerating, older adults’ brains seem to preserve what they use, at least in part. Brain aging may be compared with a complex machinery in which some often used parts are well oiled, while others less frequently used get rusty. From that perspective, brain aging is individual, shaped by our lifestyle, including our sensory experiences, reading habits, and cognitive challenges that we take on in everyday life.In addition, it shows that the brains of healthy older adults preserve their capacity to stay in tune with their surroundings.

Esther Kühn and a colleague look at a screen displaying MRI images. — The thicker a layer of the brain is, the more synapses it has, i.e. connections between nerve cells.

Older adults with a thicker layer four may compensate for declining skin sensitivity.

Esther Kühn points to a large screen displaying MRI images. — The blue area on the MRI image is the human neocortex. It shrinks with age - but layer number four does not.

A lifetime of experiences

There is another interesting aspect about the results. The pattern of brain changes that we found in older adults – a stronger sensory processing region and a reduced modulatory region – shows similarities to neurodivergent disorders such as the autism spectrum disorder or attention deficit hyperactivity disorder. Neurodivergent disorders are characterized by enhanced sensory sensitivity and reduced filtering abilities, leading to problems in concentration and cognitive flexibility. Do our findings indicate that aging drives the brain in the direction of neurodivergent disorders? Older adults´ brains have been formed by a lifetime of experiences whereas neurodivergent people are born with these brain patterns. So it would be hard to know what other effects building brain mass with age might have.

Yet our findings give us some clues about why older adults sometimes have difficulties adapting to new sensory environments. In such situations, for example being confronted with a new technical device or visiting a new city, the reduced modulatory abilities of layers five and six may become particularly evident, and may increase the likelihood for disorientation or confusion. It may also explain reduced abilities for multitasking with age, such as using a mobile phone while walking. Sensory information needs to be modulated to avoid interference when you’re doing more than one thing.

The ability to multitask declines with age.

Both the middle and the deep layers had more myelin, a fatty protective layer that is crucial for nerve function and communication, in the older mice as well as humans. This suggests that in people over the age of 65, there is a compensatory mechanism for the loss of modulatory function. This effect seemed to be breaking down in the very old mice though. Our results provide evidence for the power of a person’s lifestyle for shaping the ageing brain.

Esther Kühn from the University of Tübingen is researching how changes in the brain affect our health at the Hertie Institute for Clinical Brain Research.

She uses MRIs and other imaging techniques for this purpose. She is also a member of the German Center for Neurodegenerative Diseases (DZNE).

¹ Esther Kühn et al.: „Layer- specific changes in sensory cortex across the lifespan in mice and humans”, Nature Neuroscience, 2025, 11 August, https://doi.org/10.1038/s41593-025-02013-1

² Charles Lee, Murray Sherman: “Modulator property of the intrinsic cortical projection from layer 6 to layer 4”, Frontiers in Systems Neuroscience, 2009, Feb 26:3:3, https://doi.org/10.3389/neuro.06.003.2009

³ Ethan MacDonald, Bruce Pike: “MRI of healthy brain aging: A review”, NMR in Biomedicine, 6 June 2021, https://doi.org/10.1002/nbm.4564

Text: Esther Kühn

The current issue of Attempto! Download Attempto 63/2025, PDF, ca. 10 MB

The Pope, mathematics and infinity

Leo XIV studied mathematics and so has a deep understanding on infinity.

Obesity in the brain

Eating too many sweets or fatty foods alters the brain's hunger regulation after just a few days.