Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) symptomatology and one of its major diagnostic features (Andreasen and Flaum, 1991;DSM-IV). It has been demonstrated that the brain regions implicated in AH are involved in different aspects of language processing. This brain network includes the temporal cortex and especially the superior temporal gyrus (STG), anterior cingulate (ACC), inferior frontal gyrus (IFG), and temporo-parietal junction (TPJ). Until recently, AH were primarily controlled with antipsychotic medication which was often ineffective. In this application, we propose to use a cutting-edge biofeedback method of real-time functional imaging neuro-feedback (rt-fMRI) to reduce the frequency of AH and to better understand brain processes involved in AH. We adopt the Hugdahl 2009 model of AH according to which AH result from abnormalities in self-monitoring of speech, in selective attention and in auditory perceptual processes. We focus on the role of auditory cortex, specifically the STG, as a target area of neuro-feedback training for the treatment of AH in SZ. Based on existing literature, we posit that that improved function in the STG will normalize the entire network involved in the experience of AH. We predict that the activation in the STG (and regions forming AH network: IFG, ACC, and TPJ) will increase as a result of receiving feedback from that region which will lead to a better performance on the task of recognizing self/other voice as measured by fMRI activation levels pre-and post-rt-fMRI training and by reduction in positive symptoms and especially AH. The rt-fMRI neuro-feedback relies on recent advances in computer technology that allows subjects to see the level of activation in the selected brain region and to regulate ths activation following the training provided. Subjects are taught to up-regulate or down-regulate fMRI signal within a specific brain region selected based on the activation task. Importantly, reported activation changes are possible only if the subject receives a feedback from his/her target area and not when she/he receives it from a different subject or a different area than the target one (sham). It has been recently demonstrated that this approach may be helpful in many clinical conditions, among them schizophrenia (Haller 2010;Sitaran 2011;Linden 2012;Veit 2009;Hartwell 2012;Li 2012, Ruiz 2011). In this study we propose to study 30 chronic SZ patients and 30 normal control (NC) individuals (half of them will receive real and half will receive a sham fMRI feedback). We will use both fMRI (including two measures of connectivity) and clinical measures of the effectiveness of the rt-fMRI feedback. Based on the existing literature and our preliminary data, we predict that we will successfully improve auditory processing within the STG and within the targeted network and that it will lead to improvement in the clinical symptoms and especially in the frequency of AH.

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This application proposes to study brain processes involved in auditory hallucinations in schizophrenia, to reduce the frequency of auditory hallucinations and to improve clinical symptoms using real time fMRI feedback. We will use both fMRI self/other voice identification paradigm pre- and post fMRI feedback training session and clinical and neuropsychological measures to demonstrate the effectiveness of the fMRI feedback.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Rumsey, Judith M
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Harvard University
Schools of Medicine
United States
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Saito, Yukiko; Kubicki, Marek; Koerte, Inga et al. (2018) Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia. Brain Imaging Behav 12:229-237
Liu, Taosheng; Pinheiro, Ana P; Zhao, Zhongxin et al. (2016) Simultaneous face and voice processing in schizophrenia. Behav Brain Res 305:76-86
Pinheiro, Ana P; Rezaii, Neguine; Rauber, Andréia et al. (2014) Abnormalities in the processing of emotional prosody from single words in schizophrenia. Schizophr Res 152:235-41