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; · 4.43 Impact Factor
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ABSTRACT: Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker - the auditory brain-stem response (ABR) to complex sounds (cABR) - that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions.Frontiers in Psychiatry 10/2014; 5:142.
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ABSTRACT: Deficits in auditory and visual unisensory responses are well documented in patients with schizophrenia; however, potential abnormalities elicited from multisensory audio-visual stimuli are less understood. Further, schizophrenia patients have shown abnormal patterns in task-related and task-independent oscillatory brain activity, particularly in the gamma frequency band. We examined oscillatory responses to basic unisensory and multisensory stimuli in schizophrenia patients (N = 46) and healthy controls (N = 57) using magnetoencephalography (MEG). Time-frequency decomposition was performed to determine regions of significant changes in gamma band power by group in response to unisensory and multisensory stimuli relative to baseline levels. Results showed significant behavioral differences between groups in response to unisensory and multisensory stimuli. In addition, time-frequency analysis revealed significant decreases and increases in gamma-band power in schizophrenia patients relative to healthy controls, which emerged both early and late over both sensory and frontal regions in response to unisensory and multisensory stimuli. Unisensory gamma-band power predicted multisensory gamma-band power differently by group. Furthermore, gamma-band power in these regions predicted performance in select measures of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) test battery differently by group. These results reveal a unique pattern of task-related gamma-band power in schizophrenia patients relative to controls that may indicate reduced inhibition in combination with impaired oscillatory mechanisms in patients with schizophrenia.Frontiers in Human Neuroscience 11/2014; 8:788. · 2.90 Impact Factor