Cerebellar hypoactivation is associated with impaired sensory integration in schizophrenia.

To clarify the involvement of the cerebellum in impaired sensory integration in patients with schizophrenia, 52 first-episode patients with schizophrenia and 52 age- and sex-matched healthy controls underwent a verified sensory integration imaging task to examine the whole-brain dysfunction underlying impaired sensory integration. The familiality of cerebellar activation when integrating sensory stimuli was investigated in 25 siblings of the patients with schizophrenia, while the heritability of cerebellar activation was estimated in 56 monozygotic twins and 56 dizygotic twins. In addition, the functional connectivity between the cerebellum and the remaining regions of the whole brain was explored with psychophysiological interaction analysis. Relative to healthy controls, patients with schizophrenia showed reduced cerebellar activation when performing the sensory integration task in the whole-brain analysis. This reduced cerebellar activation was also found in the siblings of patients with schizophrenia, but to a lesser extent compared with schizophrenia patients. Cerebellar activation during sensory integration was also found to be significantly heritable. Furthermore, dysconnectivity within the cerebellum was found in patients with schizophrenia when integrating auditory and visual stimuli. These findings highlight the role of cerebellar dysfunction in the pathophysiology of schizophrenia symptoms and its potential role as an endophenotype of schizophrenia spectrum disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

[1]  Sharlene D. Newman,et al.  Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia , 2019, Schizophrenia bulletin.

[2]  D. Glahn,et al.  Neural mechanism and heritability of complex motor sequence and audiovisual integration: A healthy twin study , 2018, Human brain mapping.

[3]  Jia Huang,et al.  Neural Correlates of Audiovisual Sensory Integration , 2018, Neuropsychology.

[4]  R. Chan,et al.  Neurological soft signs precede the onset of schizophrenia: a study of individuals with schizotypy, ultra-high-risk individuals, and first-onset schizophrenia , 2018, European Archives of Psychiatry and Clinical Neuroscience.

[5]  R. Borgatti,et al.  When one is Enough: Impaired Multisensory Integration in Cerebellar Agenesis , 2016, Cerebral cortex.

[6]  R. Gur,et al.  Heritability and familiality of neurological soft signs: evidence from healthy twins, patients with schizophrenia and non-psychotic first-degree relatives , 2015, Psychological Medicine.

[7]  V. Mittal,et al.  Dysfunctional Activation of the Cerebellum in Schizophrenia , 2015, Clinical psychological science : a journal of the Association for Psychological Science.

[8]  Joseph M. Orr,et al.  Cerebellar networks in individuals at ultra high‐risk of psychosis: Impact on postural sway and symptom severity , 2014, Human brain mapping.

[9]  John Suckling,et al.  A wavelet method for modeling and despiking motion artifacts from resting-state fMRI time series , 2014, NeuroImage.

[10]  Jia Huang,et al.  Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis. , 2014, Schizophrenia bulletin.

[11]  Wen-hua Liu,et al.  Neurological soft signs discriminate schizophrenia from major depression but not bipolar disorder , 2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[12]  Jennifer K. Forsyth,et al.  Motor Deficits in Schizophrenia Quantified by Nonlinear Analysis of Postural Sway , 2012, PloS one.

[13]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[14]  A. Cachia,et al.  Correlations of cerebello‐thalamo‐prefrontal structure and neurological soft signs in patients with first‐episode psychosis , 2011, Acta psychiatrica Scandinavica.

[15]  Yue Yu,et al.  Neurological soft signs in schizophrenia: a meta-analysis. , 2010, Schizophrenia bulletin.

[16]  Jeremy D. Schmahmann,et al.  The Role of the Cerebellum in Cognition and Emotion: Personal Reflections Since 1982 on the Dysmetria of Thought Hypothesis, and Its Historical Evolution from Theory to Therapy , 2010, Neuropsychology Review.

[17]  Q. Gong,et al.  Neurological Soft Signs and Their Relationships to Neurocognitive Functions: A Re-Visit with the Structural Equation Modeling Design , 2009, PloS one.

[18]  M. Essig,et al.  Cerebellar substructures and neurological soft signs in first-episode schizophrenia , 2009, Psychiatry Research: Neuroimaging.

[19]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[20]  B. Gelder,et al.  Audiovisual emotion recognition in schizophrenia: Reduced integration of facial and vocal affect , 2009, Schizophrenia Research.

[21]  N. Andreasen,et al.  The Role of the Cerebellum in Schizophrenia , 2008, Biological Psychiatry.

[22]  Irving I. Gottesman,et al.  Neurological soft signs as candidate endophenotypes for schizophrenia: A shooting star or a Northern star? , 2008, Neuroscience & Biobehavioral Reviews.

[23]  John J. Foxe,et al.  Impaired multisensory processing in schizophrenia: Deficits in the visual enhancement of speech comprehension under noisy environmental conditions , 2007, Schizophrenia Research.

[24]  Marie-Odile Krebs,et al.  The Role of the Cerebellum in Schizophrenia: an Update of Clinical, Cognitive, and Functional Evidences , 2007, Schizophrenia bulletin.

[25]  A. Cachia,et al.  Sensory dysfunction is correlated to cerebellar volume reduction in early schizophrenia , 2007, Schizophrenia Research.

[26]  G. Venkatasubramanian,et al.  Cerebellar and other neurological soft signs in antipsychotic‐naïve schizophrenia , 2006, Acta psychiatrica Scandinavica.

[27]  L. Schad,et al.  Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia , 2005, Psychiatry Research: Neuroimaging.

[28]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[29]  J. Vroomen,et al.  Multisensory integration of emotional faces and voices in schizophrenics , 2005, Schizophrenia Research.

[30]  Robin M. Murray,et al.  Neurological soft signs in first-episode psychosis: A systematic review , 2002, British Journal of Psychiatry.

[31]  M. Hallett,et al.  Neural Correlates of Auditory–Visual Stimulus Onset Asynchrony Detection , 2001, The Journal of Neuroscience.

[32]  Yoshiro Okubo,et al.  Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia , 2001, Biological Psychiatry.

[33]  Nikos Makris,et al.  Thalamic and amygdala–hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis , 1999, Biological Psychiatry.

[34]  E. Courchesne,et al.  Prediction and preparation, fundamental functions of the cerebellum. , 1997, Learning & memory.

[35]  N C Andreasen,et al.  Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  German E Berrios,et al.  The Cambridge Neurological Inventory: A clinical instrument for assessment of soft neurological signs in psychiatric patients , 1995, Psychiatry Research.

[37]  Michael C. Neale,et al.  Methodology for Genetic Studies of Twins and Families , 1992 .

[38]  S. Resnick.  Matching for education in studies of schizophrenia. , 1992, Archives of general psychiatry.

[39]  Robert W. Buchanan,et al.  The neurological evaluation scale (NES): A structured instrument for the assessment of neurological signs in schizophrenia , 1989, Psychiatry Research.

[40]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[41]  J. Schmahmann,et al.  The neuropsychiatry of the cerebellum — insights from the clinic , 2008, The Cerebellum.

[42]  D. Manzoni,et al.  The cerebellum may implement the appropriate coupling of sensory inputs and motor responses: Evidence from vestibular physiology , 2008, The Cerebellum.

[43]  M. First,et al.  User's guide for the structured clinical interview for DSM-IV axis I disorders : SCID-I : clinical version , 1997 .

[44]  Heinrichs Dw,et al.  Significance and meaning of neurological signs in schizophrenia. , 1988 .

[45]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.