How Speech Relates to Brain Structural Changes in Psychiatric Illnesses

Post by Lila Metko 

The takeaway

Deficits in the ability to produce coherent, organized language are a common feature across many psychiatric disorders. The authors found that regardless of which specific psychiatric diagnosis an individual has, different types of deficits in their language correlate with specific changes in the brain structure. 

What's the science?

Language deficits are a feature of many psychiatric illnesses, and they span across several illness types, including both mood disorders and psychotic disorders. Formal thought disorder (FTD) is a disorder of deficits in the organization of thinking, writing, and verbal communication. Formal thought disorder and language deficits in general are associated with a poorer quality of life for individuals with psychiatric illnesses like schizophrenia spectrum disorder (SSD) or bipolar disorder. In a transdiagnostic sample - a sample containing individuals with multiple diagnoses - it was found that higher FTD disorganization is associated with lower grey matter in some regions of the brain. There have been few transdiagnostic studies that formally investigate the relationship between spoken language, the multiple dimensions of formal thought disorder, and neuroimaging analysis. This week in Molecular Psychiatry, Seuffert and colleagues used computer processing of human language to help map different features of speech onto brain structure. 

How did they do it?

The authors used natural language processing (NLP), a form of artificial intelligence to analyze and interpret language. They asked the participants, 194 with a mood disorder or psychotic disorder, and 178 healthy controls, to speak naturally to describe a set of four pictures. The total time they collected speech for each participant was 12 minutes, 3 minutes per picture. NLP was used to extract a broad set of linguistic features from each participant’s speed, which were entered into an exploratory factor analysis to identify the underlying dimensions that best explained variance across speakers. The factors were syntax complexity, richness and diversity in vocabulary, and breadth of focus in the narrative. Each participant underwent MRI imaging, and after excluding poor-quality images and artifacts, the researchers ended up with 303 participants with grey matter volume data and 247 participants with diffusion tensor imaging data. Diffusion tensor imaging is a specialized MRI technique that visualizes the diffusion of water molecules through tissue and is a particularly useful technique for visualizing the structure of white matter. 

What did they find?

The authors analyzed the relationship between the explorative analysis factors and dimensions of FTD. Syntax complexity correlated negatively with FTD Disorganization, Emptiness, and Incoherence, while vocabulary richness and diversity correlated negatively with only FTD Emptiness. This means that as these aforementioned FTD dimensions increased, the respective factors decreased. Narrow Thematic Focus (a narrow theme/narrative) was not associated with clinician-rated FTD, but showed a distinct neuroanatomical signature: a significant negative association with grey matter volume in a right-hemispheric cluster centered in the posterior insula and extending into the planum polare and putamen. No grey matter correlates were observed for the other two linguistic factors after stringent correction. In white matter analysis, each explorative analysis factor was negatively associated with functional anisotropy, a measure of white matter health, of at least one white matter tract. Vocabulary richness and diversity were associated with seven different white matter tracts, particularly within the frontotemporal regions. 

What's the impact?

This is the largest transdiagnostic study to date to map specific features of human speech onto structural brain changes in psychiatric illness. Since the quality of language is highly predictive of outcomes and quality of life in individuals with psychiatric disorders, this knowledge is especially important in the detection and treatment of these disorders. In understanding which regions of the brain are responsible for different aspects of spontaneous speech pathology, scientists are better equipped to discover treatments for them. 

How Diet Can Impact Memory Function

Post by Rebecca Glisson

The takeaway

Diets that include excessive amounts of fat or sugar can impair our memory. Receptors in the hippocampus, an area of the brain that plays a key role in memory, can become overactive with a high-fat and sugar diet, and blocking these receptors can improve memory.

What's the science?

More and more often, scientists are uncovering how our diet is linked to brain function. For example, the endocannabinoid system of the brain, which includes type-1 cannabinoid receptors (CB1Rs), is known to be overactive in people with too much fat or sugar in their diets. This week in Current Biology, Ducourneau and colleagues investigated how a poor diet can lead to memory dysfunction via the endocannabinoid system.

How did they do it?

The authors wanted to study how diet impacts memory, particularly in adolescents, a critical period for the development of memory function. They gave juvenile male mice either a diet with high-fat and high-sugar or a normal diet, then had them perform an object recognition test to evaluate their memory. The test consisted of presenting a mouse with an object, then a delay of either 3 hours to test short-term memory or 24 hours to test long-term memory, then presenting the mouse with the same object and a new object. If the mouse remembered the original object, then they spent more time exploring the new object. Mice were then injected with a CB1R receptor antagonist, which blocks the activity of this receptor, and then tested again for their memory performance.

What did they find?

Mice with high-fat and sugar diets did worse on the 24-hour long-term object recognition test than control mice. Short-term memory performance, however, was not affected by diet, as measured via a test administered only 3 hours post-exposure. This suggests that poor diets have more of an impact on long-term memory function than short-term memory. When mice on the high-sugar, high-fat diet were injected with the CB1R activity blocker, they performed better on their memory test. This suggests that CB1R is responsible for memory issues when impacted by poor diets.

What's the impact?

This study is the first to show that diets high in sugar and fat lead to long-term memory impairment via the endocannabinoid system. Further, this memory impairment can be reversed by blocking cannabinoid receptors. A poor diet is especially harmful for memory development in adolescence.

Access the original scientific publication here.

Step Count Could Lower Risk of Cognitive Decline

Post by Anastasia Sares

The takeaway

A 14-year-long study on the changes in cognition of older adults showed that for those at higher risk for cognitive decline (higher Aβ), a moderate level of activity (5,000+ steps) was associated with less cognitive decline. For these people, physical activity was linked to levels of the protein called tau in the brain, and this accounted for most of the changes in cognition.

What's the science?

Alzheimer’s disease and other dementias are an area of intense medical interest, especially now that people are living longer. There have been many studies establishing an association where greater exercise is linked to decreased cognitive decline (previous BrainPost on the subject here); however, these studies are just that—associations. There are a few elements that scientists can improve to better understand this link.

First of all, many studies are cross-sectional. That is, the data are gathered at a single point in time. So, while a cross-sectional study may sample people across different ages, they do not follow the same participants over time to see how their health evolves based on different factors. In contrast to this are longitudinal studies, which do follow participants over time, but these are relatively rare since they are more time and resource-intensive.

Second, variables like “exercise” and “memory” are often measured via a questionnaire, since this is more convenient. However, this can be problematic if respondents do not answer reliably, which is a concern when studying people with potential cognitive decline. More objective methods of measuring these variables exist: step counters are very common and can gather objective data about daily activity levels.

This week in Nature Medicine, Yau and colleagues reported the results of a longitudinal study (part of the Harvard Aging Brain Study or HABS), which included activity measured with step counters, cognitive testing, and brain imaging. They show the relationship between moderate physical activity and preserved cognitive function, along with a potential mediating mechanism in the brain.

How did they do it?

The study included 296 people from the HABS study who were cognitively unimpaired when they first signed up for the research. Participants were asked to wear a pedometer for a week near the beginning of their participation to measure their step counts. In addition, the authors selected participants who had undergone at least two rounds of cognitive testing (PACC5) as well as PET imaging at the time of the study.

PET (Positron Emission Tomography) is a neuroimaging technique used to identify different molecules in the brain with the help of a tiny amount of radioactive tracers. The researchers used PET imaging to measure levels of Aβ and tau, two proteins known to be involved in Alzheimer’s pathology. People with naturally high levels of Aβ are more at risk for cognitive decline, and the accumulation of tau proteins in the brain may be one part of that process of decline. The authors suspected that higher physical activity might be related to less accumulation of tau in the brain, which would in turn be associated with better cognition, but only for people with high Aβ (which puts them at higher risk). This kind of relationship is called a mediation.

What did they find?

Participants with low Aβ levels experienced less cognitive decline than those with high Aβ levels, and physical activity did not have much of an effect. However, for those with high Aβ, there was a significant effect of physical activity, with participants who logged more than 5,000 steps seeing the best results. Mediation analyses showed that for these people, cognitive decline was fully mediated by tau accumulation: that is, physical activity was related to less tau accumulation, and less tau was related to less cognitive decline. The activity didn’t have any further relationship with cognitive decline after accounting for the relationship with tau. The effect of activity plateaued after 5,000 steps, suggesting this is a good target for older adults to start increasing their step count.

What's the impact?

This study strengthens our confidence in the ability of exercise to stave off cognitive decline. Increasing step count is one way for older adults to improve physical activity and lower their risk of cognitive decline with aging. To further validate the effectiveness of exercise to combat aging, we need randomized controlled trials where people are assigned randomly to different levels of exercise and see whether the effect holds.

Access the original scientific publication here.