The ability to sense regular patterns is fundamental to making sense of the world. Stimulus from the environment activates a group of neurons in the frontoparietal region of the brain called the multiple demand network (MDN) that’s known to be involved in the organization and control of cognitive functions and general intelligence. Both normal aging and brain diseases can affect the MDN’s ability to detect changes or deviations from regular patterns of sensory stimuli, such as noticing that a road sign is an unusual color while driving down the highway.
New research published March 8 in The Journal of Neuroscience finds that disruption of the MDN is a common feature of various forms of dementia. According to the study, damage to any of the nodes of the MDN makes patients struggle to cope with changes in their environments, revealing a standard mechanism for this symptom.
“There has been some previous research in this direction, though most of those studies were still associative,” Nele Põldver, an experimental psychology researcher at the University of Tartu in Estonia who was not involved in the study, tells The Scientist. “Here they go a step forward and show a causal relationship between the malfunctioning of the MDN and the diminished [neurological] response.”
Dementia is a common multifactorial disease that grows increasingly likely as people age. There are several types of dementia, the most common being Alzheimer’s disease, and all can cause problems with memory, cognition, and language. Dementia can also lead to changes in mood, emotions, perception, and behavior. Although each kind of dementia is different, there are some standard features, including the loss of fundamental properties and capabilities of the brain. “Understanding the biology at the base of those similarities can help develop better treatments,” study coauthor and University of Cambridge clinical neuroscientist James Rowe tells The Scientist.
The research team set out to determine which biological changes in the brains of dementia patients correlated with a reduced ability to adapt to one’s surroundings. To do so, the researchers recruited a total of 75 patients who had been diagnosed with one of four types of dementia that affect fundamental aspects of neural activity—vision, behavior, language, and memory—plus 48 healthy controls. “It’s a very strong paper with different clinical groups representing a good range of dementia and a considerable sample size,” Põldver says.
The researchers hooked participants up to a magnetoencephalography machine (MEG), which measures the tiny magnetic fields produced by electrical currents in the brain. They then recorded participants’ brain activity as they watched the nature documentary series The Blue Planet with the sound replaced by a constant beeping that the researchers periodically interrupted with an unusual beep. The unusual beep could deviate from the regular sound in location, intensity, duration, frequency, or continuity, and each deviating beep was different from the one before it so as to avoid creating a regular pattern. The goal was to reveal how the brain automatically processes and reacts to interruptions to recurring sensory stimuli. Põldver, who often uses a similar approach in her studies, explains that it allows researchers to record simple neurological responses without requiring that study participants pay active attention. This approach allowed the researchers to show that the MDN is also responsible for performing effortless tasks in addition to more complex processes such as cognitive control, working memory, and attention.
Analyzing the data, the scientists found that the unusual sound triggered two responses in the brain: an immediate response followed by a second response around 200 milliseconds later. The initial response, which was consistent among dementia patients and healthy volunteers, indicated that the basic auditory system recognized that there was a sound. However, the second response, which reflected that the brain recognized that the sound was unusual, was much smaller in the patients, regardless of which type of dementia they had.
The team combined their MEG data with MRI scans, allowing them to map out which brain structures were activated as they watched the documentary. In the healthy subjects, neurons in the MDN domain recognized changes in sound stimuli. However, in the patients with dementia, the reduction in the second neural response was associated with damage to the MDN. Crucially, these impairments were not driven by global atrophy in auditory brain regions, as confirmed by the lack of significant correlations between the MEG data and grey matter volume. Overall, the team found that neurodegeneration reduced the brain’s capacity to interpret external sensorial stimuli (in this case, sounds) to make suppositions about what is happening in the surrounding environment, which is a property associated with the affected multiple demand nodes.
“This study provides a powerful proof-of-concept on the modulation of the brain during neurodegenerative processes like dementia. However, as [with] every neurophysiology study, it needs to get confirmed from other groups, using different techniques and samples,” Padua University neurologist Florinda Ferreri, who was not involved in the study, tells The Scientist. “We are already seeing similar results using a different approach; I think their results are robust,” Ferreri adds.
To scale up their investigation, the Cambridge researchers are teaming up with the Dementia UK Platform, a large multicenter study, to analyze a larger number of patients and follow them over time.
“Ultimately, we want to accelerate the development of new treatment[s] to help people in everyday life. Drugs that can help to tune this fundamental function of the brain—the MDN—can help people affected from dementia in their everyday life,” Rowe says. Moreover, the researchers are also looking at using similar techniques to analyze the neural activity of people at risk of developing dementia. The idea, Rowe explains, is to use the methodology on prospective patients over time and test it as a screening system to predict the onset of neurological disease.