Weakened brain connections linked to cognitive deficits in schizophrenia

Researchers have discovered a link between certain connections in the brain and cognitive function in people with early-stage psychosis and in people at high risk who later developed psychosis, according to a study published recently in Biological Psychiatry.

An estimated 23 million people worldwide have schizophrenia, according to the World Health Organization. People with schizophrenia have persistent delusions and hallucinations. Cognitive difficulties, such as memory, attention, and problem-solving, are often an early symptom of schizophrenia, appearing before the onset of psychosis and progressing as the disease progresses. Previous research has suggested that the decreased cognitive function in people with schizophrenia is related to changes in the brain.

Now, researchers from Vanderbilt University, Beth Israel Deaconess Medical Center and McLean hospital have identified the specific link between brain connectivity and cognitive function. This discovery could help lead to earlier intervention and improved treatments, researchers from the Biological Psychiatry paper said.

Researchers, led by Heather Burrell Ward, M.D., an assistant professor of psychiatry and behavioral sciences at Vanderbilt University Medical Center, examined data from patients from two large studies. The studies — the Human Connectome Project for Early Psychosis (HCP-EP) and the North American Prodrome Longitudinal Study 2 (NAPLS2) — include participants with early psychosis or at high risk for psychosis.

They analyzed data from 125 people with early psychosis and 58 matched healthy participants. To validate the results, researchers used data from 213 people at a high risk of developing psychosis and 132 healthy participants.

The participants were assessed using the Seidman Auditory Continuous Performance Task (ACPT), a cognitive test that measures attention in people with or at risk for psychotic disorders. The research team then performed scans of the brain using magnetic resonance imaging (MRI) for both groups of participants. The imaging was used to analyze participants’ neural connections to identify associations between brain connectivity and attention.

Researchers found that participants with psychosis or an increased risk for psychosis performed worse on the attention test than those who were not at risk. The scans of those with or at risk for psychosis were found to have lower connectivity between two areas of the brain: the medial prefrontal cortex, an area of the brain involved in cognitive processes, regulation of emotion, motivation, and sociability, and the somatomotor cortex, an area of the brain that processes the body’s senses.

Researchers wrote that the ability to perform on the attention test involves the translation of a cognitive process into a motor response. They found that healthy participants who did well on the attention test did not have decreased connections in these areas of the brain.

The researchers said that these links between specific areas of the brain and cognitive difficulties do not provide evidence of a causal relationship. They suggest that experimental studies using noninvasive brain stimulation techniques could help determine whether changes in these brain circuits directly impact cognitive performance.

“It is possible that specific circuits serve as rate-limiting steps during certain cognitive tasks for people with schizophrenia. If this is the case, then these circuits would serve as prime targets for intervention,” researchers wrote.

One limitation of this analysis is that the ACPT test is not a widely used cognitive assessment. Another is the small sample size of those at risk for psychosis. Researchers note that in the largest studies of people at risk for psychosis, only approximately 10% actually develop psychosis.

The study was funded by the National Institute of Mental Health.