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      Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Brain Functional Marker of Auditory Hallucinations in Schizophrenia Patients

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          Abstract

          Several cross-sectional functional Magnetic Resonance Imaging (fMRI) studies reported a negative correlation between auditory verbal hallucination (AVH) severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS). Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS) and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz) rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS) cluster, considered henceforward as a functional region of interest (fROI). After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities.

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          L Opler, Jennifer Kay, Paul Opler … (1986)
          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Computational anatomy with the SPM software.

            John Ashburner (2009)
            An overview of computational procedures for examining neuroanatomical variability is presented. The review focuses on approaches that can be applied using the SPM software package, beginning by explaining briefly how statistical parametric mapping is usually applied to functional imaging data. The review then proceeds to discuss volumetry, with an emphasis on voxel-based morphometry, and the pre-processing steps involved using the SPM software. Most volumetric studies involve univariate approaches, with a correction for some global measure, such as total brain volume. In contrast, the overall form of the brain may be more accurately modeled using multivariate approaches. Such models of anatomical variability may prove accurate enough for computer assisted diagnoses.
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              Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia.

              Simone Kühn, Jürgen Gallinat (2012)
              Auditory verbal hallucinations (AVHs) have a high prevalence in schizophrenic patients. An array of studies have explored the neural correlates of AVHs by means of functional neuroimaging and have associated AVHs with diverse brain regions, some of which have been shown to be involved in speech generation, speech perception, and auditory stimulus processing. We divided these studies into "state" studies comparing periods of presence and absence of AVHs within-subject and "trait" studies comparing patients experiencing AVHs with patients without AVHs or healthy controls during tasks with verbal material. We set out to test the internal consistency and possible dissociations of the neural correlates of AVHs. We used activation likelihood estimation to perform quantitative meta-analyses on brain regions reported in state and trait studies on AVHs to assess significant concordance across studies. State studies were associated with activation in bilateral inferior frontal gyrus, bilateral postcentral gyrus, and left parietal operculum. Trait studies on the other hand showed convergence of decreases in hallucinating subjects in left superior temporal gyrus, left middle temporal gyrus, anterior cingulate cortex, and left premotor cortex activity. Based on the clear dissociation of brain regions that show convergence across state in comparison to trait studies, we conclude that the state of experiencing AVHs is primarily related brain regions that have been implicated in speech production ie, Broca's area, whereas the general trait that makes humans prone to AVHs seems to be related to brain areas involved in auditory stimuli processing and speech perception, ie, auditory cortex.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Brain Sci
                Journal ID (iso-abbrev): Brain Sci
                Journal ID (publisher-id): brainsci
                Title: Brain Sciences
                Publisher: MDPI
                ISSN (Electronic): 2076-3425
                Publication date (Electronic): 29 April 2013
                Publication date Collection: June 2013
                Volume: 3
                Issue: 2
                Pages: 728-743
                Affiliations
                [1 ]CHU de Caen, Service Universitaire de Psychiatrie, Centre Esquirol, Caen 14000, France; E-Mails: olmaiza@ 123456yahoo.fr (O.M.); larmuriermontagne-a@ 123456chu-caen.fr (A.M.-L.)
                [2 ]Université de Caen Basse Normandie, UMR 6301 CNRS CEA, Centre Cyceron, Caen 14074, France; E-Mail: razafima@ 123456cyceron.fr
                [3 ]Université de Bordeaux, GIN UMR 5296 CNRS CEA, Bordeaux 33076, France; E-Mail: pierre-yve.herve@ 123456u-bordeaux.fr
                [4 ]CHU de Caen, Service d’Explorations Fonctionnelles du Système Nerveux, Caen 14000, France; E-Mail: etard-o@ 123456chu-caen.fr
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: dollfus-s@ 123456chu-caen.fr ; Tel.: +33-2-31-06-50-18; Fax: +33-2-31-06-49-87.
                Article
                Publisher ID: brainsci-03-00728
                DOI: 10.3390/brainsci3020728
                PMC ID: 4061846
                SO-VID: 5b531f4f-dfb7-483b-b9e6-d11ed80d4813
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 08 February 2013
                Date revision received : 15 March 2013
                Date accepted : 09 April 2013
                Categories
                Subject: Article

                Keywords: schizophrenia,auditory verbal hallucinations,functional magnetic resonance imaging,repetitive transcranial magnetic stimulation,voxel based morphometry,functional marker,language network
                Data availability:
                Keywords: schizophrenia, auditory verbal hallucinations, functional magnetic resonance imaging, repetitive transcranial magnetic stimulation, voxel based morphometry, functional marker, language network

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