Schizophrenic brains out of synch: study

Scientists at Sydney's Westmead Millenium Institute (WMI) have discovered that a rapidly-pulsed electrical signal that normally integrates the brain's many different activities 'misfires' in schizophrenia.

Associate Professor Lea Williams, director of the WMI's Brain Dynamics Centre, said her research team has shown that 40 individuals recently diagnosed with schizophrenia exhibit abnormal patterns of gamma synchrony - a 40 Hertz (40 times per second) "pacemaker" beat of electrochemical activity that sweeps across the brain.

Williams believes the resulting loss of synchrony across the brain disrupts the connectivity between the brain's functional compartments.

In a normal working human brain, multitudes of thoughts, sensations and external stimuli such as sight, smell or taste combined to form a meaningful "whole" picture of our environment.

In most people, the moment-by-moment synchronisation of rapidly cycling brain activity occur without a noticeable time lapse.

Williams said the discordant electrical activity could explain auditory hallucinations in schizophrenia - "voices from nowhere" - in terms of disrupted synchrony of the brain's visual, auditory and speech centres.

"We can think of the symptoms of schizophrenia - like hearing voices, seeing visions that others can't see, and disordered thoughts - as the orchestra not working together, so that pieces of music are jumbled up and notes are randomly associated with each other,"

Williams said her team's findings, described in a feature article in this month's issue in the highly regarded American Journal of Psychiatry, are potentially very important to the diagnosis and treatment of schizophrenia.

"It's the closest we have come to observing the brain's activity at the timescale at which people think, and what's very interesting is that patients with schizophrenia have problems putting information together at a very rapid timescale."

Williams said the study took researchers closer to linking the functional deficits in the schizophrenic brain to underlying structural abnormalities.

"The most dramatic feature of the post-mortem schizophrenic brain is that there is a dramatic reduction in the density of the dendritic spines - the tiny processes that emerge from the dendrites.

"In the normal brains there are about 300 spines per millimeter of dendrite, but in schizophrenia there are only 100 per millimeter."

Williams said it is significant that the reduced density of spines is most evident in GABA-ergic chandelier neurons, which synapse with pyramidal neurons. It is the interaction between inhibitory GABA-ergic and excitatory pyramidal neurons that generates synchronicity. The cycle of inhibition and excitation establishes the ''clock signal' or 'pacemaker' that coordinates the wave-like electrical activity across different areas of the brain.

Together, pyramidal and GABA-ergic neurons produce long-range synchrony and communication within the brain.

"There are strong reasons to speculate that this is where the loss of synchronicity arises," she said.

Williams said researchers have previously focused on identifying abnormalities in a specific region, or regions, of the brain, but there has recently been a worldwide shift towards research into the connectivity of the whole brain. Her team's discovery of an abnormality that results in a global effect on the brain is at the leading edge of schizophrenia research internationally.

The identification of a diagnostic pattern of electrical activity would also enhance prospects of more accurate diagnosis. "We can now think about earlier diagnosis, and tracking individuals as they develop schizophrenia.

"It also has implications for treatment," she said. "We know the kinds of neurochemistry involved in schizophrenia, but the limitation of current medications is that they tend to have one specific effect.

"We may need to use different drugs that bias the balance of excitatory or inhibitory activity of neurons in one direction or another.

"But the most interesting thing to me is that our discovery is very convergent - it ties together evidence from a number of independent lines of research. Everything seems to stack up."

Williams said the project also involves researchers at the University of Sydney, and Western Sydney First Episode schizophrenia program, and the Brain Resource International Database.