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Increased hippocampal, thalamic, and prefrontal hemodynamic response to an urban noise stimulus in schizophrenia.

ABSTRACT: People with schizophrenia often have difficulty ignoring unimportant noises in the environment. While experimental measures of sensory gating have yielded insight into neurobiological mechanisms related to this deficit, the degree to which these measures reflect the real-world experience of people with schizophrenia is unknown. The goal of this study was to develop a clinically relevant sensory gating paradigm and to assess differences in brain hemodynamic responses during the task in schizophrenia.Thirty-five participants, including 18 outpatients with schizophrenia and 17 healthy comparison subjects, underwent scanning on a 3-T MR system while passively listening to an "urban white noise" stimulus, a mixture of common sounds simulating a busy urban setting, including multiple conversations and events recorded from a neighborhood gathering, music, and talk radio. P50 evoked responses from a typical paired-click sensory gating task also were measured.Listening to the urban white noise stimulus produced robust activation of the auditory pathway in all participants. Activation was observed in the bilateral primary and secondary auditory cortices, medial geniculate nuclei, and inferior colliculus. Greater activation was observed in the schizophrenia patients relative to the comparison subjects in the hippocampus, thalamus, and prefrontal cortex. Higher P50 test/conditioning ratios also were observed in the schizophrenia patients. These evoked responses correlated with hemodynamic responses in the hippocampus and the prefrontal cortex.The finding of greater activation of the hippocampus, thalamus, and prefrontal cortex during a sensory gating task with high face validity further supports the involvement of these brain regions in gating deficits in schizophrenia. This link is strengthened by the observed correlation between evoked responses in the paired-click paradigm and hemodynamic responses in a functional MRI sensory gating paradigm.

SUBMITTER: Tregellas JR

PROVIDER: S-EPMC2886660 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Increased hippocampal, thalamic, and prefrontal hemodynamic response to an urban noise stimulus in schizophrenia.

Tregellas Jason R JR Ellis Jamey J Shatti Shireen S Du Yiping P YP Rojas Donald C DC

The American journal of psychiatry 20090115 3

<h4>Objective</h4>People with schizophrenia often have difficulty ignoring unimportant noises in the environment. While experimental measures of sensory gating have yielded insight into neurobiological mechanisms related to this deficit, the degree to which these measures reflect the real-world experience of people with schizophrenia is unknown. The goal of this study was to develop a clinically relevant sensory gating paradigm and to assess differences in brain hemodynamic responses during the ...[more]

PMID: 19147695

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Project description:Background"Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS).Methodology/principal findingsStudy participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls.Conclusions/significanceThese data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging.

Project description:BACKGROUND:Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses. METHODS:Forty-five healthy subjects and 62 patients with a schizophrenia spectrum disorder completed a battery of tests of executive function and underwent diffusion-weighted imaging. Probabilistic tractography was used to quantify anatomical connectivity between six cortical regions, including PFC, and the thalamus. Thalamocortical anatomical connectivity was compared between healthy subjects and patients with schizophrenia using region-of-interest and voxelwise approaches, and the association between PFC-thalamic anatomical connectivity and severity of executive function impairment was examined in patients. RESULTS:Anatomical connectivity between the thalamus and PFC was reduced in schizophrenia. Voxelwise analysis localized the reduction to areas of the mediodorsal thalamus connected to lateral PFC. Reduced PFC-thalamic connectivity in schizophrenia correlated with impaired working memory but not cognitive flexibility and inhibition. In contrast to reduced PFC-thalamic connectivity, thalamic connectivity with somatosensory and occipital cortices was increased in schizophrenia. CONCLUSIONS:The results are consistent with models implicating disrupted PFC-thalamic connectivity in the pathophysiology of schizophrenia and mechanisms of cognitive impairment. PFC-thalamic anatomical connectivity may be an important target for procognitive interventions. Further work is needed to determine the implications of increased thalamic connectivity with sensory cortex.

Dataset Information

Increased hippocampal, thalamic, and prefrontal hemodynamic response to an urban noise stimulus in schizophrenia.

Publications

Increased hippocampal, thalamic, and prefrontal hemodynamic response to an urban noise stimulus in schizophrenia.

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