brainscanPsychotic symptoms experienced by people with schizophrenia could be caused by a faulty ‘switch’ within the brain, according to research.

In a study published in the journal Neuron, scientists from the University of Nottingham have demonstrated that the severity of symptoms such as delusions and hallucinations, which are typical in patients with a diagnosis of schizophrenia, is caused by a disconnection between two regions in the brain — the insula and the lateral frontal cortex.

The breakthrough, say the academics, could form the basis for better, more targeted treatments for schizophrenia with fewer side effects.

The four-year study, led by Professor Peter Liddle and Dr Lena Palaniyappan in the University’s Division of Psychiatry and based in the Institute of Mental Health, centred on the insula region, a segregated ‘island’ buried deep within the brain, which is responsible for seamless switching between inner and outer world.

Dr Palaniyappan said: “In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex. This switch process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition. This could also explain the difficulties in ‘internalising’ external material pleasures (e.g. enjoying a musical tune or social events) that result in emotional blunting in patients with psychosis. Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms.”

Several brain regions are engaged when we are lost in thought or, for example, remembering a past event. However, when interrupted by a loud noise or another person speaking we are able to switch to using our frontal cortex area of the brain, which processes this external information. With a disruption in the connections from the insula, such switching may not be possible.

The scientists used functional MRI (fMRI) imaging to compare the brains of 38 people with schizophrenia with 35 volunteers without the condition. The results showed that whereas the majority of those without schizophrenia were able to make this switch between regions, those with the condition were less likely to shift to using their frontal cortex.

The insular and frontal cortex form a sensitive ‘salience’ loop within the brain — the insular 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.

The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could have a high degree of predictive value in identifying patients with schizophrenia.

Potential for more effective treatment

The results of the study offer information for the development of more effective treatments for the condition.

At present, treatment involves a combination of antipsychotic medications, psychological therapies and social interventions. But researchers in Nottingham are also looking at a technique called transcranial magnetic stimulation (TMS), which uses a powerful magnetic pulse to stimulate the brain regions that are malfunctioning.

Despite the insular region being buried so deeply within the brain that TMS would usually be ineffective, the results of the study suggest that the loop between the insular and frontal cortex could be exploited for TMS – if a pulse is delivered to the frontal lobe it could stimulate the insula and reset the ‘switch’.

Other future treatment options could include the use of compassion-based meditation therapy mindfulness, which may have the potential to ‘reset’ the switching function of the insula and can promote physical changes within the brain. Meditation over a long period of time has been shown to increase the folding patterns within the insula area of the brain. These ideas are in the early stages at present, but may deliver more focused treatment approaches in the longer-term.

The full paper is available online on Neuron’s website at