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IMPAIRED LOW AND HIGH-FREQUENCY OSCILLATORY ACTIVITY DURINGWORKING MEMORY IN ADOLESCENTS WITH SCHIZOPHRENIA
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Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
SESSION IV
June 22nd, 2008
Neural Synchrony as a Pathophysiological Mechanism in Schizophrenia MOLECULAR MARKERS OF CORTICAL GABA NEUROTRANSMISSION IN SCHIZOPHRENIA: REGIONAL AND CELLULAR PHENOTYPES
David A. Lewis, Takanori Hashimoto University of Pittsburgh, Pittsburgh, PA, USA [email protected] Individuals with schizophrenia exhibit disturbances in cognitive, affective, sensory and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) result, at least in part, from abnormalities in GABA neurotransmission as reflected in a specific pattern of altered expression of GABA-related genes. We sought to determine whether this pattern of altered gene expression is restricted to the DLPFC or could also contribute to the dysfunction of other cortical areas in the illness. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (DLPFC, anterior cingulate, primary motor and primary visual cortices) from subjects with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in the subjects with schizophrenia with the magnitude of the reductions for each transcript indistinguishable across the four areas. The largest reductions were detected for the mRNAs encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67 kD isoform of glutamate decarboxylase, the GABA membrane transporter 1, and the α1 and δ subunits of GABAA receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contributes to the pathophysiology, such as altered gamma band oscillations, that may underlie different clinical features of schizophrenia. NEURAL SYNCHRONY DURING PERCEPTUAL ORGANISATION IN SCHIZOPHRENIA: EEG AND MEG-STUDIES
Peter Uhlhaas Max-Planck Institute for Brain Research, Frankfurt, Germany [email protected] Introduction: Synchronization of oscillatory activity is a candidate mechanism for the coordination of neural processes in local and extended cortical circuits. Recent evidence suggests that dysfunctional neural synchrony in patients with schizophrenia may reflect a core deficit that underlies the cognitive impairments as well as the symptoms of the disorder. Methods: In the current study, we sought to extend the evidence on abnormal neural synchrony as a pathophysiological mechanism in schizophrenia through the examination of phase-synchrony and induced spectral power in electroencephalographic (EEG) and magnetoencephalographic (MEG) signals during a Gestalt perception task. We recruited a sample of patients with chronic and first-episode schizophrenia. In addition, we measured neural synchrony in a sample of healthy children and adolescents in the age range from 6-21 years to examine the development of task-related neural synchrony. Results: Behavioral impairments in patients were accompanied by pronounced deficits in local and long-rage synchronization in the theta-, beta- and gamma-band in both first-episode and chronic forms of schizophrenia. Moreover, developmental data indicated that neural
synchrony undergoes profound changes during the transition from adolescence to adulthood, suggesting a critical developmental period that may be related to the expression of psychosis during this period. Conclusions: These findings highlight the role of neural synchrony as a pathophysiological mechanism in schizophrenia that is consistent with dysfunctions in GABAergic and glutamatergic neurotransmission as well as with the neurodevelopmental profile of the disorder. Acknowledgements: This work was supported by the Max Planck Society and the BMBF (Grant: 01GWS055). References [1] Uhlhaas, PJ, Linden, DE, Singer, W, Haenschel, C, Lindner, M, Maurer, K, Rodriguez, E. (2006). Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia. J Neurosci 26: 8168-75. [2] Uhlhaas, PJ, Singer, W. (2006).N eural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron 52: 155-68. IMPAIRED LOW AND HIGH-FREQUENCY OSCILLATORY ACTIVITY DURINGWORKING MEMORY IN ADOLESCENTS WITH SCHIZOPHRENIA
Corinna Haenschel Max-Planck Institute for Brain Resarch, Frankfurt, Germany [email protected] Introduction: Impairments in working memory (WM) are regarded as a core cognitive deficit in schizophrenia. Recent models of cognition have emphasized the role of dysfunctional neural oscillations in schizophrenia. Here we investigated the relations hip between impairments in low- and high-frequency oscillations and WM using a delayed discrimination paradigm. Methods: Fourteen patients with early-onset schizophrenia and fourteen matched controls participated in a visual working memory experiment. Subjects had to encode up to three abstract shapes that were presented sequentially for 600 ms each. After a delay of 12 seconds they had to compare the memorized shapes to a test shape, which was a match in fifty percent of the trials. EEG-data were analysed for both evoked and induced oscillatory activity. Results: During WM encoding patients showed reduced posterior evoked theta, alpha and gamma oscillatory activity. Evoked gamma activity showed a WM load effect in controls only. During WM maintenance induced alpha activity increased from WM load 1 to the higher WM load conditions in controls but not in patients. During WM retrieval evoked and induced low and high-frequency oscillatory activity was again reduced in patients compared to controls. Conclusions: Pervaise deficits in neural oscillations suggest abnormalities of both perceptual and higher order cognitive functions during WM in schizophrenia. Reductions in high frequency activity in SCZ may be related to impaired perceptual integration, whereas reductions in the lower frequency range may indicate deficient long-range coordination of neural activity across the WM network. Acknowledgements: This work was supported by the Max Planck Society. References [1] Haenschel, C., P.J. Uhlhaas and W. Singer (2007)Synchronous oscillatory activity and working memory in schizophrenia. Pharmacopsychiatry, 40 Suppl 1, S54-61.
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
SESSION IV
June 22nd, 2008
Neural Synchrony as a Pathophysiological Mechanism in Schizophrenia MOLECULAR MARKERS OF CORTICAL GABA NEUROTRANSMISSION IN SCHIZOPHRENIA: REGIONAL AND CELLULAR PHENOTYPES
David A. Lewis, Takanori Hashimoto University of Pittsburgh, Pittsburgh, PA, USA [email protected] Individuals with schizophrenia exhibit disturbances in cognitive, affective, sensory and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) result, at least in part, from abnormalities in GABA neurotransmission as reflected in a specific pattern of altered expression of GABA-related genes. We sought to determine whether this pattern of altered gene expression is restricted to the DLPFC or could also contribute to the dysfunction of other cortical areas in the illness. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (DLPFC, anterior cingulate, primary motor and primary visual cortices) from subjects with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in the subjects with schizophrenia with the magnitude of the reductions for each transcript indistinguishable across the four areas. The largest reductions were detected for the mRNAs encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67 kD isoform of glutamate decarboxylase, the GABA membrane transporter 1, and the α1 and δ subunits of GABAA receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contributes to the pathophysiology, such as altered gamma band oscillations, that may underlie different clinical features of schizophrenia. NEURAL SYNCHRONY DURING PERCEPTUAL ORGANISATION IN SCHIZOPHRENIA: EEG AND MEG-STUDIES
Peter Uhlhaas Max-Planck Institute for Brain Research, Frankfurt, Germany [email protected] Introduction: Synchronization of oscillatory activity is a candidate mechanism for the coordination of neural processes in local and extended cortical circuits. Recent evidence suggests that dysfunctional neural synchrony in patients with schizophrenia may reflect a core deficit that underlies the cognitive impairments as well as the symptoms of the disorder. Methods: In the current study, we sought to extend the evidence on abnormal neural synchrony as a pathophysiological mechanism in schizophrenia through the examination of phase-synchrony and induced spectral power in electroencephalographic (EEG) and magnetoencephalographic (MEG) signals during a Gestalt perception task. We recruited a sample of patients with chronic and first-episode schizophrenia. In addition, we measured neural synchrony in a sample of healthy children and adolescents in the age range from 6-21 years to examine the development of task-related neural synchrony. Results: Behavioral impairments in patients were accompanied by pronounced deficits in local and long-rage synchronization in the theta-, beta- and gamma-band in both first-episode and chronic forms of schizophrenia. Moreover, developmental data indicated that neural
synchrony undergoes profound changes during the transition from adolescence to adulthood, suggesting a critical developmental period that may be related to the expression of psychosis during this period. Conclusions: These findings highlight the role of neural synchrony as a pathophysiological mechanism in schizophrenia that is consistent with dysfunctions in GABAergic and glutamatergic neurotransmission as well as with the neurodevelopmental profile of the disorder. Acknowledgements: This work was supported by the Max Planck Society and the BMBF (Grant: 01GWS055). References [1] Uhlhaas, PJ, Linden, DE, Singer, W, Haenschel, C, Lindner, M, Maurer, K, Rodriguez, E. (2006). Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia. J Neurosci 26: 8168-75. [2] Uhlhaas, PJ, Singer, W. (2006).N eural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron 52: 155-68. IMPAIRED LOW AND HIGH-FREQUENCY OSCILLATORY ACTIVITY DURINGWORKING MEMORY IN ADOLESCENTS WITH SCHIZOPHRENIA
Corinna Haenschel Max-Planck Institute for Brain Resarch, Frankfurt, Germany [email protected] Introduction: Impairments in working memory (WM) are regarded as a core cognitive deficit in schizophrenia. Recent models of cognition have emphasized the role of dysfunctional neural oscillations in schizophrenia. Here we investigated the relations hip between impairments in low- and high-frequency oscillations and WM using a delayed discrimination paradigm. Methods: Fourteen patients with early-onset schizophrenia and fourteen matched controls participated in a visual working memory experiment. Subjects had to encode up to three abstract shapes that were presented sequentially for 600 ms each. After a delay of 12 seconds they had to compare the memorized shapes to a test shape, which was a match in fifty percent of the trials. EEG-data were analysed for both evoked and induced oscillatory activity. Results: During WM encoding patients showed reduced posterior evoked theta, alpha and gamma oscillatory activity. Evoked gamma activity showed a WM load effect in controls only. During WM maintenance induced alpha activity increased from WM load 1 to the higher WM load conditions in controls but not in patients. During WM retrieval evoked and induced low and high-frequency oscillatory activity was again reduced in patients compared to controls. Conclusions: Pervaise deficits in neural oscillations suggest abnormalities of both perceptual and higher order cognitive functions during WM in schizophrenia. Reductions in high frequency activity in SCZ may be related to impaired perceptual integration, whereas reductions in the lower frequency range may indicate deficient long-range coordination of neural activity across the WM network. Acknowledgements: This work was supported by the Max Planck Society. References [1] Haenschel, C., P.J. Uhlhaas and W. Singer (2007)Synchronous oscillatory activity and working memory in schizophrenia. Pharmacopsychiatry, 40 Suppl 1, S54-61.