Megan A Perrin1, Joshua T Kantrowitz2, Gail Silipo3, Elisa Dias3, Omar Jabado4, Daniel C Javitt5. 1. Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research, United States; Department of Clinical Neuropsychology, Queens College, United States; The Graduate Center, City University of New York, United States. 2. Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research, United States; Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, United States. 3. Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research, United States. 4. Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, United States. 5. Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research, United States; Department of Psychiatry, Columbia College of Physicians and Surgeons, United States. Electronic address: dcj2113@columbia.edu.
Abstract
Persistent auditory verbal hallucinations (AVH) in schizophrenia are increasingly tied to dysfunction at the level of auditory cortex. AVH may reflect in part misattribution of internally generated thoughts to external spatial locations. Here, we investigated the association between persistent AVH and spatial localization abilities assessed both behaviorally and by mismatch negativity (MMN) to location deviants. METHODS: Spatial- and tonal- discrimination abilities were assessed in patients (n=20) and controls (n=20) using free-field tones. MMN was assessed to spatial-location-, pitch- and duration-deviants. AVH and thought disorder were assessed using clinical evaluation. RESULTS: As predicted, patients showed significant reductions in behavioral spatial-discrimination (p<0.0001) and tone-matching (p<0.001) ability, along with impaired MMN generation to location (p<0.03) and pitch (p<0.05) deviants. Hallucinating (AVH+) and non-hallucinating (AVH-) subjects showed similar deficits in location MMN to left-hemifield stimuli (p<0.0001 vs. control). By contrast, AVH- patients differed significantly from controls (p=0.009) and AVH+ patients (p=0.018) for MMN to right-lateral hemifield (left auditory cortex) stimuli, whereas AVH+ patients showed paradoxically preserved MMN generation (p=0.99 vs. controls). Severity of thought disorder correlated with impaired spatial discrimination, especially to right-hemifield stimuli (p=0.013), but did not correlate significantly with MMN or tone matching deficits. CONCLUSION: These findings demonstrate a significant relationship between auditory cortical spatial localization abilities and AVH susceptibility, with relatively preserved function of left vs. right auditory cortex predisposing to more severe AVH, and support models that attribute persistent AVH to impaired source-monitoring. The findings suggest new approaches for therapeutic intervention for both AVH and thought disorder in schizophrenia.
Persistent auditory verbal hallucinations (AVH) in schizophrenia are increasingly tied to dysfunction at the level of auditory cortex. AVH may reflect in part misattribution of internally generated thoughts to external spatial locations. Here, we investigated the association between persistent AVH and spatial localization abilities assessed both behaviorally and by mismatch negativity (MMN) to location deviants. METHODS: Spatial- and tonal- discrimination abilities were assessed in patients (n=20) and controls (n=20) using free-field tones. MMN was assessed to spatial-location-, pitch- and duration-deviants. AVH and thought disorder were assessed using clinical evaluation. RESULTS: As predicted, patients showed significant reductions in behavioral spatial-discrimination (p<0.0001) and tone-matching (p<0.001) ability, along with impaired MMN generation to location (p<0.03) and pitch (p<0.05) deviants. Hallucinating (AVH+) and non-hallucinating (AVH-) subjects showed similar deficits in location MMN to left-hemifield stimuli (p<0.0001 vs. control). By contrast, AVH- patients differed significantly from controls (p=0.009) and AVH+ patients (p=0.018) for MMN to right-lateral hemifield (left auditory cortex) stimuli, whereas AVH+ patients showed paradoxically preserved MMN generation (p=0.99 vs. controls). Severity of thought disorder correlated with impaired spatial discrimination, especially to right-hemifield stimuli (p=0.013), but did not correlate significantly with MMN or tone matching deficits. CONCLUSION: These findings demonstrate a significant relationship between auditory cortical spatial localization abilities and AVH susceptibility, with relatively preserved function of left vs. right auditory cortex predisposing to more severe AVH, and support models that attribute persistent AVH to impaired source-monitoring. The findings suggest new approaches for therapeutic intervention for both AVH and thought disorder in schizophrenia.
Authors: Pejman Sehatpour; Daniel C Javitt; Heloise M De Baun; Marlene Carlson; Anna Beloborodova; David H Margolin; Mark B L Carlton; Nicola L Brice; Joshua T Kantrowitz Journal: Neuropsychopharmacology Date: 2021-10-20 Impact factor: 8.294
Authors: Natalie de la Garrigue; Juliana Glasser; Pejman Sehatpour; Dan V Iosifescu; Elisa Dias; Marlene Carlson; Constance Shope; Tarek Sobeih; Tse-Hwei Choo; Melanie M Wall; Lawrence S Kegeles; James Gangwisch; Megan Mayer; Stephanie Brazis; Heloise M De Baun; Stephanie Wolfer; Dalton Bermudez; Molly Arnold; Danielle Rette; Amir M Meftah; Melissa Conant; Jeffrey A Lieberman; Joshua T Kantrowitz Journal: J Psychiatr Brain Sci Date: 2020-08-06
Authors: Pejman Sehatpour; Michael Avissar; Joshua T Kantrowitz; Cheryl M Corcoran; Heloise M De Baun; Gaurav H Patel; Ragy R Girgis; Gary Brucato; Javier Lopez-Calderon; Gail Silipo; Elisa Dias; Antigona Martinez; Daniel C Javitt Journal: Front Psychiatry Date: 2021-02-02 Impact factor: 4.157