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  • Researchers analyzed the patterns of brain activity evoked by movie scenes in people with schizophrenia.
  • The researchers report that in the brains of individuals without schizophrenia, mental concepts are organized into semantic domains and related concepts are connected, enabling coherent thought and speech.
  • In people with schizophrenia, these semantic networks appeared to be disrupted, resulting in incoherent speech and delusions.
  • This study provides the first biological evidence for the “loosening of associations” theory of schizophrenia and may potentially be used to understand the biological basis of other mental disorders as well as the creative processes of exceptionally talented individuals.

Schizophrenia is a mental health condition characterized by hallucinations, delusion (inaccurate interpretation of reality), and incoherent speech.

The term schizophrenia was coined in 1908 by Eugen Bleuler, a Swiss psychiatrist. Bleuler believed that the fundamental feature of schizophrenia was the “loosening of associations,” or lack of association between different ideas that resulted in disorganized thinking.

In the brains of individuals without schizophrenia, ideas, words, and phrases that share a common meaning or are related in some way (semantically related) are connected to form “semantic networks.” For example, some semantically related concepts to the word red could be green, fire engine or apple.

In schizophrenia, typical connections in the brain are “loosened” and unrelated concepts are connected.

Although the theory of loosening of associations is accepted within the medical community, during the past 100 years since its inception, doctors have not found proof that there are specific brain characteristics that cause it.

Now, with the help of functional magnetic resonance imaging (fMRI) and natural language processing (NLP) techniques, researchers at Tokyo Medical and Dental University (TMDU) led by Dr. Hidehiko Takahashi, a professor and chairperson of the Department of Psychiatry at TMDU, have elucidated the specific brain characteristics linked to the loosening of associations in schizophrenia.

The results of their study were published in the journal Schizophrenia Bulletin.

In comments to Medical News Today, Dr. Edwin Fuller Torrey, a research psychiatrist specializing in schizophrenia and bipolar disorder, described this study as being “among the more interesting recent studies of schizophrenia.”

Functional magnetic resonance imaging (fMRI) is a brain imaging technique that uses magnetic fields to measure changes in blood flow to different areas of the brain.

These changes in blood flow are thought to reflect changes in neural activity, allowing researchers to identify which areas of the brain are activated during different mental tasks or stimuli.

The researchers in the recent study investigated the brain activity of 14 people with schizophrenia (age 24–59 years, mean = 44 years; 43% females) and 17 other individuals (age 26–49 years, mean = 40 years; 59% females).

All the participants with schizophrenia were free of co-morbid psychiatric disorders and all were taking antipsychotic medications. The other individuals were matched with the patient group by age, sex, educational background, and predicted IQ.

All of the participants underwent fMRI procedures while watching soundless color movies of natural scenes projected on a screen in the MRI scanner. The movies consisted of various types of clips (animals, nature, film scenes) that lasted 10 to 20 seconds each.

Based on the patterns of fMRI activity, the researchers identified how different concepts were represented in the brain.

Using graph theory-based network analysis, the researchers analyzed the similarity of the neural activity patterns evoked by different words in different brain regions and constructed semantic brain networks.

The researchers then evaluated various network measures, such as clustering coefficient, characteristic path length, “small worldness,” and modularity, to understand how different concepts are connected in the brain.

The researchers reported that the semantic brain networks of healthy individuals have the characteristics of “small-world networks.”

An analogy for how a small-world network functions is a group of children playing the telephone game where the message spreads quickly because all the children are connected.

In the brains of people without schizophrenia, concepts are organized into specific semantic domains and are globally connected, enabling coherent thought and speech.

In contrast, the researchers reported that the semantic networks of people with schizophrenia were disorganized and randomized. These impairments in semantics and associations contribute to delusion and incoherent speech.

The researchers also found a correlation between semantic brain network measures and psychological variables. The more the semantic brain networks were disrupted, the more severe were the person’s delusions.

In their paper, the researchers state that “this is the first study to construct semantic networks based on brain responses and to quantitatively evaluate the differences in network structure between schizophrenia patients and healthy controls.”

They added that the findings provide the first biological evidence for the “loosening of associations” theory of schizophrenia, which manifests as loss of coherence in brain activity during word processing.

This is a potentially important observation because it means that a medical professional can measure the loosening of associations and, in principle, track people’s responses to treatment, on the one hand — and “understand functional disconnections in schizophrenia in terms of the underlying (synaptic) mechanisms, on the other”, according to Karl Friston, FRSB, FRS, a study coauthor and professor of imaging neuroscience as well as a principal research fellow at University College London.

“These findings pave the way for neural biomarkers of schizophrenia that could illuminate factors related to risk, progression and treatment,” added Jessica Andrews-Hanna, Ph.D., an associate professor of cognition and neural systems at the University of Arizona.

Furthermore, the researchers said they hope that their method will facilitate the future investigation of “the altered or creative inner experiences of individuals with mental illness or exceptional abilities, respectively, which thus far, have been accessible only through verbal reports and behavior.”

The study had some limitations.

First, participants were allowed to move their eyes freely during the study. As a result, any potential differences in attentional focus among patients could have influenced the recorded fMRI signal.

Second, the patients were taking antipsychotic medications, which may have influenced their brain responses to the movies in a manner specific to the drug they were taking.

Lastly, patient age varied, which may have led to inconsistencies in the severity, chronicity, and burden of their conditions.

Fuller Torrey told MNT that while the study findings provide “a logical explanation for the existence of loose associations […], what has to happen next, as noted by the authors themselves, is to repeat the study using patients not on antipsychotics to verify that what they are measuring is not simply a drug effect. It should probably also be repeated in another country to verify that the semantic brain networks are not specific to the Japanese language.”

Andrews-Hanna commented to MNT that “[a]s the sample size is small and several demographic and methodological factors may have influenced the results, it will be important for future studies to replicate the findings […] in larger cohorts of participants across a variety of language-based tasks.”