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Posted by Phillipa on September 6, 2013, at 0:01:17
Medscape Medical News > PsychiatryFaulty Brain Switch May Spark Schizophrenia Hallucinations
Deborah Brauser
Sep 03, 2013
An inability to effectively "switch" between key brain regions when processing new information may explain why patients with schizophrenia commonly experience delusions and hallucinations, suggests new imaging research.A study of 73 adults who underwent resting functional magnetic resonance imaging (fMRI) showed that those with schizophrenia had "a significant failure of both the feedforward and reciprocal influence" between the insula and the dorsolateral prefrontal cortex (DLPFC) compared with their healthy peers.
In addition, the participants with schizophrenia also showed a breakdown in processing from the bilateral visual cortices to the insula.
"For many years, it has been known that the most consistent brain tissue reduction in patients with schizophrenia occurs in the insula. But to date, no satisfactory explanation was possible for the role it played in the pathophysiology of psychosis," lead author Lena Palaniyappan, MD, told Medscape Medical News.
"These results offer a convincing model of what goes wrong in the region that is often seen as the junction of cognition and emotion in the human brain," added Dr. Palaniyappan, who is associate director at the Center for Translational Neuroimaging at the Institute of Mental Health at the University of Nottingham in the United Kingdom.
He noted that the findings also have potential treatment implications for the disorder and offer "great promise for targeted neuromodulation approaches," including the use of transcranial magnetic stimulation (TMS).
"Most of the TMS treatment trials in schizophrenia have focused on treating positive symptoms (hallucinations) by targeting temporal cortex. Now the time has come to undertake targeted treatment trials that can improve crucial connectivity disturbances."
The study was published in the August 21 issue of Neuron.
Dysfunctional Switching
Approximately 1 in 100 individuals are affected by schizophrenia, the authors write. Although it is considered to be one of the most common serious mental health conditions, scientists remain unsure of its cause.
The common belief is that it is due to a combination of genetic, environmental, and drug use factors. However, maternal complications during pregnancy have also been suspected.
Although a combination of antipsychotic medications, talk therapy, and social interventions are called for in treating this condition, only 1 in 5 patients achieve complete recovery.
Dr. Lena Palaniyappan
For this study, the researchers enrolled 38 adult patients with schizophrenia (76% men; mean age, 34.5 years) and 35 adults without the disorder ("control group"; 71% men; mean age, 33.5 years) from the United Kingdom. All participants underwent resting fMRI scans.
Results showed that after experiencing outside stimuli, the majority of the control group were able to switch seamlessly between brain regions to better process the new data. However, those with schizophrenia were less likely to shift to using their frontal cortex.
"The insular and frontal cortex form a sensitive 'salience' loop within the brain the insula should stimulate the frontal cortex while in turn the frontal cortex should inhibit the insula but in patients with schizophrenia this system was found to be seriously compromised," explained the researchers in a release.
In other words, the patients with schizophrenia showed no significant functional connectivity between the right anterior insula (rAI) and the right temporal pole and a significant anticorrelation between the rAI and the left temporal pole (P < .001). The control group showed a significant positive correlation in both areas (both, P < .001).
There were also significant group differences in correlations between the DLPFC and the rAI.
"Powerful Mechanistic Explanation"
"These findings provide compelling evidence for a breakdown of the salience-execution loop in the clinical expression of psychosis," write the investigators.
They add that the results also help to explain the commonly seen "frontal inefficiency," which is the term used when patients with schizophrenia fail to recruit their prefrontal system when new information becomes available.
"In clinical practice, we often tell patients that the symptoms of schizophrenia result from a chemical imbalance," said Dr. Palaniyappan. "While this offers an explanation to some features of the illness, it does not satisfactorily explain a number of experiences that are central to schizophrenia and most disturbing in the long term."
He added that the results clarify that faulty connections among the brain networks "prevent effective transition between the internal and external world."
"Consequently, patients find it difficult to disengage from their internal experiences and process information from the outside world to engage in external social pleasures," such as a song on the radio or various social events, and can lead to emotional blunting, he said.
In the release, he noted that the faulty switching process may also explain why internal thoughts sometimes appear as external reality, shown in hallucinations, delusions, or voices.
"Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms," said Dr. Palaniyappan.
The study was funded by a grant from the Medical Research Council and by a research fellowship from the Wellcome Trust to Dr. Palaniyappan. The study authors have disclosed no relevant financial relationships.
Neuron. 2013;79:814-828. Full article
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