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ABSTRACT: Schizophrenia is characterized by widespread cognitive deficits that reflect distributed dysfunction across multiple cortical regions. Here the authors examined the relationship between lower- and higher-level dysfunction within the auditory domain using the event-related brain potentials mismatch negativity (MMN) and P300.
Event-related brain potentials were obtained from 50 schizophrenia patients and 21 healthy subjects in two conditions: a standard condition employing fixed differences between standard tones and pitch deviants and a novel individualized condition employing tones matched to each individual's tone-discrimination threshold. The relationship among measures was assessed by multiple regression analysis and structural equation modeling.
In the standard fixed-deviance condition, schizophrenia patients showed deficits of large effect size in generation of MMN (d>1.26) and P300 (d=1.08) relative to comparison subjects. Assessment of deviance-detection thresholds showed that patients required significantly elevated tone-matching thresholds relative to comparison subjects (d=0.97). When tone differences were individually adjusted to equate tone-matching performance across groups, the groups no longer differed significantly in MMN amplitude during deviant pitch tones, and the degree of deficit in P300 generation was significantly reduced. In both multiple regression analysis and structural equation modeling, MMN and diagnostic group were significant independent predictors of reduced P300 amplitude. MMN generation was well explained (>90% variance) by dipoles seeded within the bilateral auditory cortex.
These findings confirm and extend previous reports of impaired basic sensory processing in schizophrenia and demonstrate significant contributions of early sensory processing dysfunction to higher-order cognitive impairments. Overall, the findings support distributed, hierarchical models of cognitive impairment in schizophrenia, consistent with glutamatergic and other widespread neurochemical models of the disorder.
American Journal of Psychiatry 07/2010; 167(7):818-27. · 12.54 Impact Factor
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ABSTRACT: functional magnetic resonance imaging results all localized the IC effect to bilateral LOC areas. We propose that IC sensitivity described in V2 and V1 may reflect predominantly feedback modulation from higher-tier LOC areas, where IC sensitivity first occurs. Two additional observations further support this proposal. The latency of the IC effect shifted dramatically later (#120 msec) when stimuli were laterally presented, indicating that retinotopic position alters IC processing. Immediately preceding the IC effect, the VEP modulated with inducer eccentricity---the configuration effect. We interpret this to represent contributions from global stimulus parameters to scene analysis. In contrast to the IC effect, the topography of the configuration effect was restricted to central parieto--occipital scalp. Key words: event-related potentials; ERP; VEP; dipoles; fMRI; Kanizsa; lateral--occipital cortex; LOC Object recognition occurs despite ambiguous or incomplete information in the ret
10/2003;
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ABSTRACT: Schizophrenia is associated with well-documented deficits in high-order cognitive processes such as attention and executive functioning. The integrity of sensory-level processing, however, has been evaluated only to a limited degree. Our study evaluated the ability of patients with schizophrenia to recognize complete objects based on fragmentary information, a process termed perceptual closure. Perceptual closure processes are indexed by closure negativity (N(cl)), a recently defined event-related potential (ERP) component that is generated within the visual association cortex. This study assessed the neural integrity of perceptual closure processes in schizophrenia by examining N(cl) generation. Generation of the preceding positive (P1) and negative (N1) ERP components was also examined.
We evaluated 16 patients with chronic schizophrenia and 16 healthy comparison subjects. Successively less fragmented images were presented during high-density ERP recording, which permitted the monitoring of brain activity during perceptual closure processes prior to object recognition. Analyses were performed at parieto-occipital and occipitotemporal sites consistent with dorsal and ventral stream generators of P1, N1, and N(cl).
Patients with schizophrenia showed significant impairment in the ability to recognize fragmented objects, along with impaired generation of N(cl). The amplitude of visual P1 was significantly reduced, particularly over dorsal stream sites. In contrast, the generation of visual N1 was intact.
Patients with schizophrenia are profoundly impaired in perceptual closure as indicated by both impaired performance and impaired N(cl) generation. The selective impairment in dorsal stream P1 is consistent with prior reports of impaired magnocellular processing in schizophrenia. By contrast, intact ventral N1 generation suggests that the initial stages of ventral stream processing are relatively preserved and that impaired magnocellular dorsal stream functioning in schizophrenia may lead to secondary dysregulation of ventral stream object recognition processing.
Archives of General Psychiatry 12/2002; 59(11):1011-20. · 12.02 Impact Factor
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ABSTRACT: Because environmental information is often suboptimal, visual perception must frequently rely on the brain's reconstruction of contours absent from retinal images. Illusory contour (IC) stimuli have been used to investigate these "filling-in" processes. Intracranial recordings and neuroimaging studies show IC sensitivity in lower-tier area V2, and to a lesser extent V1. Some interpret these data as evidence for feedforward processing of IC stimuli, beginning at lower-tier visual areas. On the basis of lesion, visual evoked potentials (VEP), and neuroimaging evidence, others contend that IC sensitivity is a later, higher-order process. Whether IC sensitivity seen in lower-tier areas indexes feedforward or feedback processing remains unresolved. In a series of experiments, we addressed the spatiotemporal dynamics of IC processing. Centrally presented IC stimuli resulted in early VEP modulation (88-100 msec) over lateral-occipital (LOC) scalp--the IC effect. The IC effect followed visual response onset by 40 msec. Scalp current density topographic mapping, source analysis, and functional magnetic resonance imaging results all localized the IC effect to bilateral LOC areas. We propose that IC sensitivity described in V2 and V1 may reflect predominantly feedback modulation from higher-tier LOC areas, where IC sensitivity first occurs. Two additional observations further support this proposal. The latency of the IC effect shifted dramatically later (approximately 120 msec) when stimuli were laterally presented, indicating that retinotopic position alters IC processing. Immediately preceding the IC effect, the VEP modulated with inducer eccentricity--the configuration effect. We interpret this to represent contributions from global stimulus parameters to scene analysis. In contrast to the IC effect, the topography of the configuration effect was restricted to central parieto-occipital scalp.
Journal of Neuroscience 07/2002; 22(12):5055-73. · 7.11 Impact Factor
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ABSTRACT: : Ingestion of the nonproteinic amino acid theanine (5-N-ethylglutamine) has been shown to increase oscillatory brain activity in the so-called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established.
: Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task.
: As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition.
: This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system.
Clinical Neuropharmacology 30(1):25-38. · 2.17 Impact Factor
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ABSTRACT: Recent studies show that in addition to enhancing neural processing for attentionally relevant stimuli, selective attention also operates by suppressing the processing of distracter stimuli. When subjects are pre-cued to selectively deploy attention during voluntary (endogenous) attentional tasks, these mechanisms can be set up in advance of actual stimulus processing. That is, the brain can be placed in a biased attentional state. Two recent cueing studies have provided evidence for the deployment of such biased attentional states [J.J. Foxe, G.V. Simpson, S.P. Ahlfors, Neuroreport 9 (1998) 3929–3933; M.S. Worden, J.J. Foxe, N. Wang, G.V. Simpson, J. Neurosci. 20:RC63 (2000) 1–6]. Specifically, these studies implicated oscillatory activity in the alpha frequency-band (8–14 Hz) as an anticipatory mechanism for suppressing distracter visual stimulation. The current study extends these findings by showing that this alpha-suppressive effect is also invoked by cross-modal cues. Auditory symbolic cues were used in an intermodal attention task, to direct subjects’ attention to a subsequent task in either the visual or auditory modality. Cueing attention to the auditory features of the imminent task stimuli resulted in significantly higher parieto–occipital alpha amplitude in the period preceding onset of this stimulus than when attention was cued to the visual features. Topographic mapping suggests that this effect is generated in regions of the inferior parietal cortex, areas that have been repeatedly implicated in the engagement and maintenance of visual attention. Taken together, the results of this series of studies suggest that these parietal regions are capable of integrating sensory cues from multiple sensory modalities in order to program the subsequent deployment of visual attention.
Cognitive Brain Research.