When doors of perception close: bottom-up models of disrupted cognition in schizophrenia
ABSTRACT Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of schizophrenia and a primary cause of long-term disability. Current neurophysiological models of schizophrenia focus on distributed brain dysfunction with bottom-up as well as top-down components. Bottom-up deficits in cognitive processing are driven by impairments in basic perceptual processes that localize to primary sensory brain regions. Within the auditory system, deficits are apparent in elemental sensory processing, such as tone matching following brief delay. Such deficits lead to impairments in higher-order processes such as phonological processing and auditory emotion recognition. Within the visual system, deficits are apparent in functioning of the magnocellular visual pathway, leading to higher-order deficits in processes such as perceptual closure, object recognition, and reading. In both auditory and visual systems, patterns of deficit are consistent with underlying impairment of brain N-methyl-d-aspartate receptor systems.
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ABSTRACT: Background: Superior temporal cortices include brain regions dedicated to auditory processing and several lines of evidence suggest structural and functional abnormalities in both schizophrenia and bipolar disorder within this brain region. However, possible glutamatergic dysfunction within this region has not been investigated in adult patients. Methods: Thirty patients with schizophrenia (38.67 ± 12.46 years of age), 28 euthymic patients with bipolar I disorder (35.32 ± 9.12 years of age), and 30 age-, gender- and education- matched healthy controls were enrolled. Proton Magnetic Resonance Spectroscopy data were acquired using a 3.0T Siemens MAGNETOM TIM Trio MR system and single voxel Point Resolved Spectroscopy Sequence (PRESS) in order to quantify brain metabolites within the left and right Heschl Gyrus and Planum Temporale of superior temporal cortices. Results: There were significant abnormalities in Glutamate (Glu) (F(2,78)=8.52, p<0.0001), n- Acetyl Aspartate (tNAA) (F(2,81)=5.73, p=0.005), Creatine (tCr) (F(2,83)=5.91, p=0.004) and Inositol (Ins) (F(2,82)=8.49, p<0.0001) concentrations in the left superior temporal cortex. In general, metabolite levels were lower for bipolar disorder patients when compared to healthy participants. Moreover, patients with bipolar disorder exhibited significantly lower tCr and Ins concentrations when compared to schizophrenia patients. In addition, we have found significant correlations between the superior temporal cortex metabolites and clinical measures. Conclusion: As the left auditory cortices are associated with language and speech, left hemisphere specific abnormalities may have clinical significance. Our findings are suggestive of shared glutamatergic abnormalities in schizophrenia and bipolar disorder.Schizophrenia Research 02/2015; 161(2-3). DOI:10.1016/j.schres.2014.11.012 · 4.43 Impact Factor
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ABSTRACT: Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test–retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n = 824, SZ n = 966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP recordings were obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d = 0.96) and P3a (d = 0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies.Schizophrenia Research 10/2014; 163(1-3). DOI:10.1016/j.schres.2014.09.042 · 4.43 Impact Factor
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ABSTRACT: An increasing number of studies investigate the visual mismatch negativity (vMMN) or use the vMMN as a tool to probe various aspects of human cognition. This paper reviews the theoretical underpinnings of vMMN in the light of methodological considerations and provides recommendations for measuring and interpreting the vMMN. The following key issues are discussed from the experimentalist's point of view in a predictive coding framework: (1) experimental protocols and procedures to control "refractoriness" effects; (2) methods to control attention; (3) vMMN and veridical perception.Frontiers in Human Neuroscience 01/2014; 8:666. DOI:10.3389/fnhum.2014.00666 · 2.90 Impact Factor