Left temporo-limbic and orbital dysfunction in schizophrenia during odor familiarity and hedonicity judgments

Impairments of olfactory processing in patients with schizophrenia (SZ) have been reported in various olfactory tasks such as detection, discrimination, recognition memory, identification, and naming. The purpose of our study was to determine whether impairments in odor familiarity and hedonicity judgments observed in SZ patients during a previous behavioral study are associated with modifications of the activation patterns in olfactory areas. Twelve SZ patients, and 12 healthy comparison (HC) subjects, were tested using the H2(15)O-PET technique and 48 different odorants delivered during 8 scans. In addition to an odorless baseline condition, they had either to detect odor, or to judge odor familiarity or hedonicity, giving their responses by pressing a button. Regional cerebral blood flows during olfactory conditions were compared with those for baseline condition. Between-group analyses were then performed, and completed by regions of interest analyses. Both groups had equivalent ability for the detection of suprathreshold odorants, but patients found odors less familiar, and pleasant odors less pleasant than HC subjects. These behavioral results were related to functional abnormalities in temporo-limbic and orbital olfactory regions lateralized in the left hemisphere: the posterior part of the piriform cortex and orbital regions for familiarity judgments, the insular gyrus for hedonicity judgments, and the left inferior frontal gyrus and anterior piriform cortex/putamen region for the three olfactory tasks. They mainly resulted from a lack of activation during task conditions in the SZ patients. These data could explain olfactory disturbances and other clinical features of schizophrenia such as anhedonia.

[1]  J. Pardo,et al.  Elucidating Dynamic Brain Interactions with Across-Subjects Correlational Analyses of Positron Emission Tomographic Data: The Functional Connectivity of the Amygdala and Orbitofrontal Cortex during Olfactory Tasks , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  Carlo Caltagirone,et al.  Chronic schizophrenia as a brain misconnection syndrome: a white matter voxel-based morphometry study , 2003, Schizophrenia Research.

[3]  R. McCarley,et al.  A review of MRI findings in schizophrenia , 2001, Schizophrenia Research.

[4]  R. Bressan,et al.  Validity study of the Brazilian version of the Calgary Depression Scale for Schizophrenia , 1998, Schizophrenia Research.

[5]  C. Huron,et al.  Impairment of constructive memory in schizophrenia , 2002, International clinical psychopharmacology.

[6]  N. Edelstyn,et al.  Investigation of Conscious Recollection, False Recognition and Delusional Misidentification in Patients with Schizophrenia , 2003, Psychopathology.

[7]  N. Andreasen,et al.  Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients , 2000, Schizophrenia Research.

[8]  Ivanka Savic,et al.  Imaging of brain activation by odorants in humans , 2002, Current Opinion in Neurobiology.

[9]  G. Paxinos,et al.  Atlas of the Human Brain , 2000 .

[10]  J. Royet,et al.  A stimulation method using odors suitable for PET and fMRI studies with recording of physiological and behavioral signals , 2005, Journal of Neuroscience Methods.

[11]  Matthew Flatt,et al.  PsyScope: An interactive graphic system for designing and controlling experiments in the psychology laboratory using Macintosh computers , 1993 .

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

[13]  I. Tendolkar,et al.  Remembering or knowing: electrophysiological evidence for an episodic memory deficit in schizophrenia , 2002, Psychological Medicine.

[14]  Brain imaging studies of the functional organization of human olfaction. , 2002, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[15]  Robert J Zatorre,et al.  Olfactory learning: convergent findings from lesion and brain imaging studies in humans. , 2002, Brain : a journal of neurology.

[16]  D. Zald The human amygdala and the emotional evaluation of sensory stimuli , 2003, Brain Research Reviews.

[17]  G. Rizzolatti,et al.  Both of Us Disgusted in My Insula The Common Neural Basis of Seeing and Feeling Disgust , 2003, Neuron.

[18]  W. Honer,et al.  Olfactory hallucinations and olfactory identification ability in patients with schizophrenia and other psychiatric disorders , 1994, Schizophrenia Research.

[19]  M R Sperling,et al.  Olfactory dysfunction in schizophrenia and temporal lobe epilepsy. , 2001, Neuropsychiatry, neuropsychology, and behavioral neurology.

[20]  Vincent Magnotta,et al.  Regional frontal abnormalities in schizophrenia: a quantitative gray matter volume and cortical surface size study , 2000, Biological Psychiatry.

[21]  Ron Kikinis,et al.  Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter , 1999, Biological Psychiatry.

[22]  Karl J. Friston,et al.  The left medial temporal region and schizophrenia. A PET study. , 1992, Brain : a journal of neurology.

[23]  Bruce R. Rosen,et al.  Activation and Habituation in Olfaction—An fMRI Study , 2001, NeuroImage.

[24]  J. Daléry,et al.  Ratings of different olfactory judgements in schizophrenia. , 2002, Chemical senses.

[25]  J. Royet,et al.  Lateralization of olfactory processes. , 2004, Chemical senses.

[26]  Gilles Sicard,et al.  Functional Anatomy of Perceptual and Semantic Processing for Odors , 1999, Journal of Cognitive Neuroscience.

[27]  N. Makris,et al.  Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. , 1999, Archives of general psychiatry.

[28]  M. Lepage,et al.  Is associative recognition more impaired than item recognition memory in Schizophrenia? A meta-analysis , 2003, Brain and Cognition.

[29]  B. Turetsky,et al.  Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. , 2000, Archives of general psychiatry.

[30]  A. Clair,et al.  Neuropsychological, neurological and symptom correlates of impaired olfactory identification in schizophrenia , 1998, Schizophrenia Research.

[31]  Ralf Deichmann,et al.  Functional Heterogeneity in Human Olfactory Cortex: An Event-Related Functional Magnetic Resonance Imaging Study , 2002, The Journal of Neuroscience.

[32]  N. Costes,et al.  Emotional Responses to Pleasant and Unpleasant Olfactory, Visual, and Auditory Stimuli: a Positron Emission Tomography Study , 2000, The Journal of Neuroscience.

[33]  B. Turetsky,et al.  Reduced olfactory bulb volume in patients with schizophrenia. , 2000, The American journal of psychiatry.

[34]  M. Hautzinger,et al.  Olfactory event-related potentials in psychosis-prone subjects. , 1993, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[35]  B. Turetsky,et al.  Dysregulation of olfactory receptor neuron lineage in schizophrenia. , 2001, Archives of general psychiatry.

[36]  A. Holley,et al.  Functional Neuroanatomy of Different Olfactory Judgments , 2001, NeuroImage.

[37]  B T Hyman,et al.  Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. , 1991, Archives of general psychiatry.

[38]  J. D. E. Gabrieli,et al.  Sniffing and smelling: separate subsystems in the human olfactory cortex , 1998, Nature.

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

[40]  M. Serby,et al.  Olfactory sense in psychoses , 1990, Biological Psychiatry.

[41]  J. Pardo,et al.  Functional neuroimaging of the olfactory system in humans. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[42]  Robin M. Murray,et al.  Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation , 1997, Psychological Medicine.

[43]  W. Honer,et al.  Left nostril olfactory identification impairment in a subgroup of male patients with schizophrenia , 1998, Schizophrenia Research.

[44]  Karl J. Friston,et al.  453 Mapping of gray matter changes in schizophrenia , 1997, Schizophrenia Research.

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

[46]  G Kobal,et al.  Olfactory functional imaging and physiology. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[47]  L. Kopala,et al.  Regional Metabolism in Microsmic Patients with Schizophrenia * , 1991, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

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

[49]  Yasushi Miyashita,et al.  From Perception to Sentence Comprehension: The Convergence of Auditory and Visual Information of Language in the Left Inferior Frontal Cortex , 2002, NeuroImage.

[50]  Robert J. Zatorre,et al.  Functional Imaging of the Chemical Senses , 2000 .

[51]  R. Gervais,et al.  Learning‐induced Changes in Rat Piriform Cortex Activity Mapped Using Multisite Recording With Voltage Sensitive Dye , 1997, The European journal of neuroscience.

[52]  G. Mandler Recognizing: The judgment of previous occurrence. , 1980 .

[53]  B. Turetsky,et al.  Impairment of odor hedonics in men with schizophrenia. , 2003, The American journal of psychiatry.

[54]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[55]  N. Ravel,et al.  Spatiotemporal distribution of a late synchronized activity in olfactory pathways following stimulation of the olfactory bulb in rats , 1998, The European journal of neuroscience.

[56]  Richard S. J. Frackowiak,et al.  Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. , 2002, The American journal of psychiatry.

[57]  L. Kopala,et al.  Sex differences in olfactory function in schizophrenia , 1989 .

[58]  J. Mazziotta,et al.  Brain mapping : the systems , 2000 .

[59]  J. Daléry,et al.  Olfactory identification deficiency and WCST performance in men with schizophrenia , 1998, Psychiatry Research.

[60]  R. Huws,et al.  Olfactory acuity in the positive and negative syndromes of schizophrenia , 1991, Biological Psychiatry.

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

[62]  I. Savic,et al.  Passive perception of odors and semantic circuits , 2004, Human brain mapping.

[63]  Ivanka Savic,et al.  Processing of odorous signals in humans , 2001, Brain Research Bulletin.

[64]  Chantal Delon-Martin,et al.  Involvement of right piriform cortex in olfactory familiarity judgments , 2005, NeuroImage.

[65]  S. Paradiso,et al.  Emotions in unmedicated patients with schizophrenia during evaluation with positron emission tomography. , 2003, The American journal of psychiatry.

[66]  J. Pardo,et al.  Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[67]  David A. Kareken,et al.  Olfactory system activation from sniffing: effects in piriform and orbitofrontal cortex , 2004, NeuroImage.

[68]  A. Levy,et al.  Hypometabolism in olfactory cortical projection areas of male patients with schizophrenia: an initial positron emission tomography study , 1996, Psychiatry Research.

[69]  B. Turetsky,et al.  Physiologic impairment of olfactory stimulus processing in schizophrenia , 2003, Biological Psychiatry.

[70]  Michael D Rugg,et al.  Remembrance of Odors Past Human Olfactory Cortex in Cross-Modal Recognition Memory , 2004, Neuron.

[71]  S. Carmichael,et al.  Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys , 1996 .

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

[73]  M. Strauss,et al.  Emotional response as a function of symptoms in schizophrenia , 1998, Schizophrenia Research.

[74]  J. Gorman,et al.  SPECT imaging of odor identification in schizophrenia , 1998, Psychiatry Research: Neuroimaging.

[75]  Chantal Delon-Martin,et al.  fMRI of emotional responses to odors: influence of hedonic valence and judgment, handedness, and gender , 2003, NeuroImage.

[76]  D. Kareken,et al.  Functional anatomy of human odor sensation, discrimination, and identification in health and aging. , 2003, Neuropsychology.