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MRI, PET Map Source of Schizophrenia Symptoms.

NEW YORK -- Using functional MRI and PET, it is possible to map the locations in the brain that are active during hallucinations and delusions--the core symptoms of schizophrenia, Dr. David A. Silbersweig said at a schizophrenia conference sponsored by Columbia University and the New York State Psychiatric Institute.

He presented findings from several imaging studies, which showed that hallucinations were associated with specific patterns of activity in sensory association cortices and mesolimbic and subcortical regions. Paranoid delusions were associated with an inappropriate mesolimbic threat response to neural stimuli.

Dr. Silbersweig described a 23-year-old patient with visual and auditory verbal hallucinations who had never taken antipsychotic drugs. The patient was scanned with PET in a dark, quiet room during active hallucinations and while not hallucinating. When compared with healthy controls, the scans during active hallucinations showed clear activity in visual and auditory-linguistic association cortices (Nature 378[6553]:176-79, 1995)

"Brain regions that are active in healthy controls only when they are seeing and hearing things in the external environment were active in this schizophrenic patient in a dark, quite room while he was hallucinating," Dr. Silbersweig said. Even though hallucinations may seem bizarre, subjective, and ephemeral, the patient is experiencing them and is responding logically to what his brain is telling him, he said.

In addition to brain areas that become activated in the absence of external stimuli, it appears that other brain areas have decreased activity. Dr. Silbersweig's imaging studies have found that an area of the prefrontal cortex involved in monitoring and controlling the temporal lobe is less active than it should be. This may be contributing to the production of hallucinations.

One theory of hallucinations suggests that they are a result of internal dialogue perceived to be coming from the outside. To test this, Dr. Silbersweig and his colleagues at New York Weill Cornell Medical Center, New York, asked subjects to perform an inner speech task during PET imaging (Br. J. Psychiatry 169[2]:148-59, 1996). They compared schizophrenic patients with a history of hallucinations, schizophrenic patients with no history of hallucinations, and normal controls. When imagining sentences spoken in another person's voice, the normal subjects and the nonhallucinating schizophrenics had strong activation in the left middle temporal gyrus and the rostral supplementary motor region. Hallucinators had reduced activity in these regions.

"These findings suggest that the areas involved in monitoring and assessing inner speech are not functioning properly in patients with schizophrenia," he said.

More recent imaging studies have shed light on the neural basis of delusions. The amygdala appears to play a role in assessing verbal and nonverbal cues indicating a threat. It has been hypothesized that in schizophrenics the brain mistakenly labels nonthreatening stimuli as threatening.

Dr. Silbersweig and his colleagues devised an imaging study to compare schizophrenic patients actively paranoid at the time of the scan, schizophrenic patients who were not actively paranoid, and healthy controls. Patients were asked to name the color of words that were either threatening or neutral. In controls, activation of the amygdala was significantly greater while naming the color of threatening words. In paranoid schizophrenic patients, the amygdala was activated while naming the color of both threatening and neutral words. The ventromedial prefrontal cortex, which is involved in modulating the activity of the amygdala, was not active enough.
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Publication:Clinical Psychiatry News
Date:Sep 1, 2001
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