Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study

Abstract Background Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. Methods We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. Results The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. Conclusions The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia.

[1]  A. Sawa,et al.  Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium , 2016, Translational psychiatry.

[2]  B. Turetsky,et al.  Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia , 2015, Schizophrenia Research.

[3]  G. Cagney,et al.  Reduced protein synthesis in schizophrenia patient-derived olfactory cells , 2015, Translational Psychiatry.

[4]  G. Juckel,et al.  Olfactory function and morphology of olfactory epithelium in an adult population with schizophrenia , 2015, Schizophrenia Research.

[5]  Jonathan D. Power,et al.  Recent progress and outstanding issues in motion correction in resting state fMRI , 2015, NeuroImage.

[6]  Yaakov Stern,et al.  Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community , 2015, Neurology.

[7]  Vince D. Calhoun,et al.  Thalamus and posterior temporal lobe show greater inter-network connectivity at rest and across sensory paradigms in schizophrenia , 2014, NeuroImage.

[8]  Jonathan D. Power,et al.  Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high‐motion data points , 2014, Human brain mapping.

[9]  S. Berretta,et al.  Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia , 2013, Schizophrenia Research.

[10]  Michael Schocke,et al.  Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease. , 2013, Brain : a journal of neurology.

[11]  H. Bickeböller,et al.  Odor naming and interpretation performance in 881 schizophrenia subjects: association with clinical parameters , 2013, BMC Psychiatry.

[12]  J. Ogloff,et al.  A case-linkage study of crime victimisation in schizophrenia-spectrum disorders over a period of deinstitutionalisation , 2013, BMC Psychiatry.

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

[14]  J. Gottfried Central mechanisms of odour object perception , 2010, Nature Reviews Neuroscience.

[15]  Karin E. Borgmann-Winter,et al.  Scents and nonsense: olfactory dysfunction in schizophrenia. , 2009, Schizophrenia bulletin.

[16]  John-Dylan Haynes,et al.  Odor quality coding and categorization in human posterior piriform cortex , 2009, Nature Neuroscience.

[17]  D. Dietrich,et al.  Audiovisual integration of speech is disturbed in schizophrenia: An fMRI study , 2009, Schizophrenia Research.

[18]  C. Tanner,et al.  Association of olfactory dysfunction with risk for future Parkinson's disease , 2008, Annals of neurology.

[19]  R. Kikinis,et al.  Occipital lobe gray matter volume in male patients with chronic schizophrenia: A quantitative MRI study , 2007, Schizophrenia Research.

[20]  C. Pantelis,et al.  Olfactory sensitivity through the course of psychosis: Relationships to olfactory identification, symptomatology and the schizophrenia odour , 2007, Psychiatry Research.

[21]  Jane Plailly,et al.  Left temporo-limbic and orbital dysfunction in schizophrenia during odor familiarity and hedonicity judgments , 2006, NeuroImage.

[22]  R. Woods,et al.  Cortical Thinning in Cingulate and Occipital Cortices in First Episode Schizophrenia , 2005, Biological Psychiatry.

[23]  T. R. Stratford Activation of feeding-related neural circuitry after unilateral injections of muscimol into the nucleus accumbens shell , 2005, Brain Research.

[24]  David R Roalf,et al.  Decrements in volume of anterior ventromedial temporal lobe and olfactory dysfunction in schizophrenia. , 2003, Archives of general psychiatry.

[25]  C. Pantelis,et al.  Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia. , 2003, The American journal of psychiatry.

[26]  G. Glover,et al.  Dissociated neural representations of intensity and valence in human olfaction , 2003, Nature Neuroscience.

[27]  L. Magrum,et al.  GABAA and GABAB receptors in the anterior piriform cortex modulate feeding in rats , 2002, Brain Research.

[28]  S. Paradiso,et al.  Neural mechanisms of anhedonia in schizophrenia: a PET study of response to unpleasant and pleasant odors. , 2001, JAMA.

[29]  Raquel E Gur,et al.  Olfactory Dysfunction in Schizophrenia: A Qualitative and Quantitative Review , 1999, Neuropsychopharmacology.

[30]  K. Davis,et al.  Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. , 1997, Archives of general psychiatry.

[31]  C. Pantelis,et al.  Neuropsychological, olfactory, and hygiene deficits in men with negative symptom schizophrenia , 1996, Biological Psychiatry.

[32]  J. Price,et al.  Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys , 1995, The Journal of comparative neurology.

[33]  J. Price,et al.  Central olfactory connections in the macaque monkey , 1994, The Journal of comparative neurology.

[34]  D. S. Zahm,et al.  The patterns of afferent innervation of the core and shell in the “Accumbens” part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro‐gold , 1993, The Journal of comparative neurology.

[35]  L. Kopala,et al.  Olfactory deficits in neuroleptic naive patients with schizophrenia , 1993, Schizophrenia Research.

[36]  S. Potkin,et al.  Olfactory memory in unmedicated schizophrenics , 1993, Schizophrenia Research.

[37]  D. Javitt,et al.  Recent advances in the phencyclidine model of schizophrenia. , 1991, The American journal of psychiatry.

[38]  David P. Salmon,et al.  Olfactory thresholds are associated with degree of dementia in Alzheimer's disease , 1990, Neurobiology of Aging.

[39]  L. Kopala,et al.  Olfactory deficits in schizophrenia , 1988, Biological Psychiatry.

[40]  A. Hoffer,et al.  Olfactory changes in schizophrenia. , 1962, The American journal of psychiatry.

[41]  N. E. Stratas Fluphenazine in chronic refractory schizophrenics. , 1962, The American journal of psychiatry.

[42]  R. Jardri,et al.  Resting-state functional connectivity of the nucleus accumbens in auditory and visual hallucinations in schizophrenia. , 2015, Schizophrenia bulletin.

[43]  Karin E. Borgmann-Winter,et al.  Meta-analysis of olfactory function in schizophrenia, first-degree family members, and youths at-risk for psychosis. , 2014, Schizophrenia bulletin.

[44]  B. Turetsky,et al.  Odor hedonic capacity and anhedonia in schizophrenia and unaffected first-degree relatives of schizophrenia patients. , 2013, Schizophrenia bulletin.

[45]  M. Jones-Gotman,et al.  The human brain distinguishes between single odorants and binary mixtures. , 2009, Cerebral cortex.

[46]  Noam Sobel,et al.  Attentional modulation in human primary olfactory cortex , 2005, Nature Neuroscience.