Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia

OBJECTIVE Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia. METHODS Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired-stimulus conditioning-test paradigm were obtained from the same subjects. RESULTS Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure. CONCLUSIONS Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia.

[1]  K. Kultas‐Ilinsky,et al.  Distribution of GABAB binding sites in the thalamus and basal ganglia of the rhesus monkey (Macaca mulatta) , 1999, Neuropharmacology.

[2]  O. Vinogradova,et al.  [Sensory characteristics of the cortical input to the hippocampus: the entorhinal cortex]. , 1975, Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova.

[3]  P. Teale,et al.  Source origin of a 50-msec latency auditory evoked field component in young schizophrenic men , 1988, Biological Psychiatry.

[4]  Robert Freedman,et al.  Varied effects of atypical neuroleptics on P50 auditory gating in schizophrenia patients. , 2004, The American journal of psychiatry.

[5]  Robert T. Knight,et al.  Prefrontal cortex gating of auditory transmission in humans , 1989, Brain Research.

[6]  J S Buchwald,et al.  Midlatency auditory evoked responses in the human and the cat model. , 1987, Electroencephalography and clinical neurophysiology. Supplement.

[7]  R. Freedman,et al.  Medial septal neuron activity in relation to an auditory sensory gating paradigm , 1993, Neuroscience.

[8]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[9]  C. Elger,et al.  Short-term habituation of the intracranially recorded auditory evoked potentials P50 and N100 , 2004, Neuroscience Letters.

[10]  Lei Wang,et al.  Abnormalities of thalamic activation and cognition in schizophrenia. , 2006, The American journal of psychiatry.

[11]  B. Maher,et al.  Progress in experimental personality research , 1964 .

[12]  Erwin Rj,et al.  Midlatency auditory evoked responses in the human and the cat model. , 1987 .

[13]  E Jefferson Sensory gating in the human hippocampal and rhinal regions , 2005 .

[14]  E. Bramon,et al.  Meta-analysis of the P300 and P50 waveforms in schizophrenia , 2004, Schizophrenia Research.

[15]  F. Benes,et al.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. , 1991, Archives of general psychiatry.

[16]  Gregory A. Miller,et al.  M50 sensory gating predicts negative symptoms in schizophrenia , 2005, Schizophrenia Research.

[17]  L Kruglyak,et al.  Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Robert Freedman,et al.  Elementary neuronal dysfunctions in schizophrenia , 1991, Schizophrenia Research.

[19]  R. Freedman,et al.  Neurophysiologic studies of sensory gating in schizophrenia: Comparison of auditory and visual responses , 1985, Biological Psychiatry.

[20]  J. Buchwald,et al.  Depth evoked potential and single unit correlates of vertex midlatency auditory evoked responses , 1983, Brain Research.

[21]  A. Mcghie,et al.  Disorders of attention and perception in early schizophrenia. , 1961, The British journal of medical psychology.

[22]  P. Venables,et al.  INPUT DYSFUNCTION IN SCHIZOPHRENIA. , 1964, Progress in experimental personality research.

[23]  J. Stein Progress in clinical neurophysiology Vol. 4. Cerebral motor control in man: Long loop mechanisms. Edited by J. E. Desmedt. S. Karger, Basel, 1979, 394 pp. $70.75 , 1980, Neuropsychologia.

[24]  A. Scheibel,et al.  The organization of the nucleus reticularis thalami: a Golgi study. , 1966, Brain research.

[25]  G. A. Miller,et al.  Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia. , 2003, The American journal of psychiatry.

[26]  Stephan Heckers,et al.  Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia , 2006, Schizophrenia Research.

[27]  R. Freedman,et al.  Effects of sound intensity on a midlatency evoked response to repeated auditory stimuli in schizophrenic and normal subjects. , 1995, Psychophysiology.

[28]  G. V. Simpson,et al.  Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems , 1993, Brain Research.

[29]  Ruben C. Gur,et al.  Midlatency auditory evoked responses in schizophrenia , 1991, Biological Psychiatry.

[30]  R Freedman,et al.  Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. , 1983, Biological psychiatry.

[31]  R. Freedman,et al.  The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli , 1995, Neuroscience.

[32]  G. A. Miller,et al.  Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia , 2003, Clinical Neurophysiology.

[33]  D. Glahn,et al.  Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia , 2005, Human brain mapping.

[34]  Vinogradova Os,et al.  [Sensory characteristics of the cortical input to the hippocampus: the entorhinal cortex]. , 1975 .

[35]  H. Holcomb,et al.  Probing the human hippocampus using rCBF: Contrasts in schizophrenia , 2001, Hippocampus.

[36]  G. A. Miller,et al.  Cross-modal generality of the gating deficit. , 2005, Psychophysiology.

[37]  H. Holcomb,et al.  Correlations Between rCBF and Symptoms in Two Independent Cohorts of Drug-Free Patients with Schizophrenia , 2006, Neuropsychopharmacology.

[38]  R. Weisskoff,et al.  Improved auditory cortex imaging using clustered volume acquisitions , 1999, Human brain mapping.

[39]  N. Alpert,et al.  Impaired recruitment of the hippocampus during conscious recollection in schizophrenia , 1998, Nature Neuroscience.

[40]  R Freedman,et al.  Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. , 1982, Biological psychiatry.

[41]  Thomas Grunwald,et al.  Neuronal substrates of sensory gating within the human brain , 2003, Biological Psychiatry.

[42]  K. Kultas‐Ilinsky,et al.  Distribution of GABA(B) binding sites in the thalamus and basal ganglia of the rhesus monkey (Macaca mulatta). , 1999, Neuropharmacology.

[43]  B Kollmeier,et al.  Auditory brainstem responses with optimized chirp signals compensating basilar-membrane dispersion. , 2000, The Journal of the Acoustical Society of America.

[44]  Robert Freedman,et al.  Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study. , 2004, The American journal of psychiatry.