The science of cognitive deviations

A new non-invasive behavioral test by Caltech researchers provides early detection Alzheimer's disease Risk by analyzing how individuals cope with deviations, providing a breakthrough in early disease management.

Alzheimer's disease is a neurodegenerative disease that impairs a person's ability to think, remember, and perform basic functions. according to National Institutes of HealthAlzheimer's disease affects more than 6 million Americans, most of whom are 65 years of age or older. Although the nerve damage caused by the disease cannot be reversed, its progression can be slowed with early interventions such as exercise and nutrition programs. Therefore, early detection of Alzheimer's disease risk may be essential to help people manage and plan for their symptoms.

Challenges of early detection

However, before the physical symptoms of Alzheimer's appear, the main way to measure an individual's risk of developing the disease is to measure the levels of certain proteins in the cerebrospinal fluid (higher levels indicate a higher risk). This test is invasive, painful and expensive.

Breakthrough in behavioral testing

A team from the California Institute of Technology and the Huntington Medical Research Institutes is currently leading a project to develop a simple behavioral test to detect a person's risk of developing Alzheimer's disease, a test that is as non-invasive as solving a computer puzzle. In 2022, the team developed a behavioral test whose results correlate precisely with cerebrospinal fluid measurements.

Show another GIF of a typical attempt. “Ready” indicates the start of the trial. Participants are asked to name the color of the underlined word, or to name the word itself if it is not underlined. Each trial contains two words, and a noise-masked high-speed prime is presented before the second word. Masking is one way researchers use to make things “invisible”: meaningless symbols occupy the same location as the word “invisible” and flash just before and after the word. The brain focuses on the loud and bright stimulus and unconsciously processes only the hidden word. Credit: Courtesy of S. Hong

Now the team has used the test to learn more about the ability of people at high risk to pay attention and concentrate. The work is described in an article published in the journal GyroscienceIt suggests that at-risk individuals use their attention to process distracting stimuli rather than suppress them. The research was conducted in the Caltech laboratory of Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology. Shimojo is an affiliate faculty member at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

New testing approach

“Every researcher in this field has dreamed of proposing a highly sensitive psychological model to detect subtle pre-symptoms in high-risk older adults,” says Shimojo. “However, this was almost impossible because these elderly people are so vulnerable no It is diagnosed through current official standard tests. Our success is due to two new developments: first, implicit cognitive processing that requires attention. Second, the hypothesis that cognitive deficits will only reveal themselves under high workload.

In the test, the participant performs what is called a Stroop paradigm task. This is a popular puzzle in which a person is shown a word (the word is the name of a color) displayed on a computer screen as colored text. However, the word itself does not necessarily correspond to the color in which it is displayed. For example, the word “RED” can be displayed in green. In each repetition of the task, the participant was asked to name either the color of the word or the word itself. Compared to naming the word itself, naming the color of text is a bit of a “slog” – it's harder than it looks. (You can try it yourself below.)

What does this word say? What color is this word? Is it easier to read the word or say its color? Credit: S. Hong

But the researchers also added an extra twist to make the task more difficult. Just before the actual target was presented, a word (white on a white background and “obscured” by several nonsense symbols) flashed rapidly on the screen, too quickly for the participant to consciously detect it. (See the video to the right of the text for an example.)

The blank word—technically called an “implicit distraction”—is intended to unconsciously distract the participant. In addition to the conscious and deliberate collection of information, known as “overt perception,” our brains have the ability to process sensory information without us being aware of it. This is called “implicit cognition.”

Study results and their implications

The study included 36 people with an average age of 75 and in good cognitive health. Each underwent a myriad of tests related to Alzheimer's risk: brain MRIs, genome sequencing, and the aforementioned invasive spinal fluid measurements. Based on these biological markers, individuals can be classified as high or low risk.

In a 2022 study, the team found that people at high risk for Alzheimer's disease (as measured by their spinal fluid levels) slowed by about 5% in the presence of implicit distraction in high-effort conditions. This implicit interference has not been found in low-risk individuals. These findings suggest that implicit cognition may be impaired years before classic Alzheimer's disease symptoms appear.

A diagram of the test, divided into still images. Credit: S. Hong

The new study focused on understanding how Subjects used their attention during the test. Think of attention as a kind of currency, a limited resource your mind can spend. We've all found that our attention gets distracted from a specific task. Maybe notifications from your phone or a noisy room will distract you from reading this article right now. The team aims to determine whether high-risk populations are paying attention practical The distracting word instead of removing and blocking the distraction.

“Your brain will subconsciously recognize the distracting word whether you have a high or low risk of developing Alzheimer's disease,” says Shao Min (Shun) Hong, a former postdoctoral researcher in Shimojo's group and now an assistant professor at Waseda University in Japan. and co-first author of the study. “But we wanted to study what your brain does next? Are you using your efforts to eliminate the distraction or are you using your efforts to process the distraction? Healthy people at risk for cognitive impairment should be able to suppress the distraction.”

To examine this, the team asked the same volunteers to complete the task twice, two weeks apart. The idea is that practical It reduces the mental load of the task and allows you to have more available attention. For example, if you are an experienced soccer player, you may be able to dribble the ball easily while using some of your attention to process other elements in your environment. But if you are new to soccer, you need to use a lot of attention and concentration to dribble the ball correctly. Practice frees your mind's attention to use it elsewhere.

The researchers found that after practicing the task, the low-risk individuals used their extra attention respression The word is distracting and therefore less distracting. On the contrary, individuals at risk pay special attention to themselves practical Distraction word: absorbing unnecessary information that distracts them from the task at hand and leads to greater interference with their performance. These distractions did not lead to significantly poorer overall performance, but the distraction was evident, as high-risk individuals who had a training effect (faster on the second task) slowed more in the presence of the distracting word.

“These findings suggest a strong link between implicit cognition and attention, and that changes in implicit cognition in a high-risk population may reflect a very early change in how attention is used,” Hong explains.

Sarah Adams (BS'21), a research assistant at Caltech, is a co-first author with Hong. Besides Hong, Adams, and Shimojo, other co-authors are Kathleen Molloy and Xianghong Arakaki of the Huntington Medical Research Institutes and Caltech senior scientist Dao-An Wu (PhD '06). Funding was provided by a James Boswell Postdoctoral Fellowship, a Postdoctoral Fellowship in Biology and Bioengineering at Caltech, and the alignment of consciousness research with the US funding mechanisms of the Templeton Global Philanthropies, the Whittier Foundation, and the National Institutes of Health.