ERC research lends an ear to the voices heard by schizophrenia patients The ERC-funded ONOFF project is building upon previous efforts to better understand auditory hallucinations (AH) in patients with schizophrenia. Its results could lead to new cognitive and pharmacological treatments. Health © ESB Professional, Shutterstock In 70 % of cases, schizophrenia appears alongside AH. Patients start hearing one or more voices inside their head, and they would often describe how these voices keep arguing with them or telling them what to do. From VOICE to ONOFF Prof. Kenneth Hugdahl’s research taught us that the perception of these voices found a neuronal origin in the temporal lobe on the left side of the brain. And he has kept advancing the scientific understanding of this symptom ever since. Under the VOICE project – completed in 2015 – Prof. Hugdahl notably obtained a first glimpse at the neurochemistry of AH. He uncovered how its onset was accompanied by hyper-excitation in voice areas and hypo-activation in the inhibition areas of the brain. Now, with its second ERC Advanced grant for ONOFF (Perception of voices that do not exist: Tracking the temporal signatures of auditory hallucinations), the Founder of Bergen fMRI Group is trying to explain one of the most intriguing characteristics of AH, its fluctuation over time. “Following the findings of the VOICE project, it struck me that most, if not all research efforts have so far focused on explaining what caused the onset of a hallucinatory episode,” Prof. Hugdahl explains. “What I observed, however, was that hallucinatory episodes seem to fluctuate over time. For me, it was clear that if the onset of an episode had neurobiological markers, it was also possible that the offset of an episode could have corresponding markers, although for some reason the process was reversed.” It didn’t take much more for Prof. Hugdahl to kick-start the ONOFF in 2016. Since then, the project has seen the launch of a brief questionnaire to get information on AH fluctuations over time and a phone app asking questions related to the key dimensions of AH. It carried out the following: used a Norwegian population study on the incidence of AHs in the general population to find out about potential environmental triggers; devised a method to see if changes in brain activation (measured with fMRI) had corresponding changes in neurotransmitter levels (measured with MRS); tried out a training app for patients to increase their cognitive control over the ‘voices’; and observed on and off AH fluctuations in patients within an MR scanner. Tangible findings already Although the project is only set for completion in 2021, it has already led to interesting results. The positive correlation between glutamate/glutamin levels in the voice areas in the brain and severity of AHs found in the VOICE project was verified. The team found a negative correlation between glutamate/glutamin levels and severity of AHs in an area of the brain’s frontal lobe related to top-down cognition and inhibitory control. Thanks to the smartphone app, Prof. Hugdahl could also observe that as patients indicate that the level of distress is increasing, the feeling of cognitive control of the ‘voice’ is going down, and vice versa. This indicates that the use of app technology can help obtain more detailed data on the relationship between stress and control. Eventually, ONOFF research could inspire treatment approaches to pharmacologically prolong OFF-periods by blocking hyper-excitation and/or boost hypo-excitation. Besides, the use of the dichotic listening training app could help improve cognitive control. “Since schizophrenia is a heterogeneous disorder with clinical, cognitive and brain symptoms, it is important to aim at developing new treatments at different levels of explanation, and I believe that a combination of cognitive and pharmacological treatments will have the best effects,” Prof. Hugdahl concludes. Keywords ONOFF, VOICE, schizophrenia, auditory hallucinations, fluctuation, cognitive control, brain, glutamate/glutamin, smartphone app
