Date Published: 22 August 2013

Schizophrenia symptoms associated with disconnection between the insula and the lateral frontal cortex in the brain

Health News from the United Kingdom (UK).

Schizophrenia has been described as one of the most common serious mental health conditions. It is thought to affect around 1 in 100 people. In many cases the first indications of schizophrenia occur in a patient's late teens or early 20s. This can have devastating consequences for the person's future.

Research has recently revealed that psychotic symptoms experienced by people with schizophrenia could be caused by a faulty 'switch' within the brain - according to scientists at Nottingham University (England, UK) who have recently completed a 4-year research study concerning the insula region of the brain, which is a segregated 'island' buried deep within the brain. It is responsible for 'seamless switching between inner and outer world'.

The study was led by Professor Peter Liddle and Dr Lena Palaniyappan who have demonstrated that the severity of symptoms such as delusions and hallucinations which are typical in patients with the psychiatric disorder schizophrenia is caused by a disconnection between two important regions in the brain ? the insula and the lateral frontal cortex. They have suggested that this discovery might eventually result in better and more targeted treatments for schizophrenia that have fewer adverse side effects.

Dr Lena 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.

More about schizophrenia and the recent research

Compromised brain function

The insular and frontal cortex of the brain normally 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 compromised. The scientists used functional MRI (fMRI) imaging to compare the brains of 35 healthy volunteers with those of 38 schizophrenic patients. The results showed that while most of the healthy patients were able to make this switch between regions, those diagnosed with schizophrenia were less likely to shift to using their frontal cortex. The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could help to predict patients who might develop schizophrenia.

Genetic and environmental triggers

The causes of schizophrenia remain unknown but scientists believe that they could involve a combination of a genetic predisposition to the condition with environmental factors. Drug use is known to be a trigger ? people who use cannabis, or stimulant drugs, are three to four times more likely to go on to develop recurrent psychotic symptoms. It is also believed that underdevelopment of the brain in the womb caused by complications in the mother's pregnancy and in early childhood linked to issues such as malnutrition could play a key part. Previous observations from this research group have also revealed the presence of unusually smooth folding patterns of the brain over the insula region in patients, suggesting an impairment in the normal development of this structure in schizophrenia.

At present (2013), treatment involves a combination of antipsychotic medications, psychological therapies and social interventions. Only 20% patients with schizophrenia achieve complete recovery and many patients who develop the condition in the long-term struggle to find a treatment that is completely effective in managing their condition. Antipsychotic drugs, though effective in a number of patients, have poor acceptance rates due to the burden of unwanted side effects that often results in patients ceasing using the medication over the long-term, followed by recurrence of disabling symptoms.

Researchers are also investigating transcranial magnetic stimulation (TMS), a technique that uses a powerful magnetic pulse to stimulate the brain regions that are malfunctioning.

Compassion-based therapies

Despite the fact that the insular region is buried so deeply within the brain that TMS would usually be ineffective, the results of the recent study at Nottingham University suggest that the loop between the insular and the 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 a compassion-based meditation therapy called 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 its early stages at present, but may deliver more focussed treatment approaches in the longer term.

Ref. to Paper
Neural Primacy of the Salience Processing System in Schizophrenia, is available online on Neuron's website at

Source: Nottingham University, England -

Also in the News:

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Cognitive therapy found safe to treat schizophrenia - 6 Feb '14

Research into genetic causes of schizophrenia within families - 17 Jan '12

Schizophrenia linked to mutations in the gene for VIPR2 - 23 Feb '11

Research aims to slash waiting times for young people with mental illness - 3 Sep '10

Rare genetic variations involving whole sections of DNA implicated in autism - 10 Jun '10

South Wales' first self-management course for those with long-term mental health issues - 3 Feb '10

Schizophrenia: it's not just “in the genes” - 15 Feb '09

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