Early Sensory Contributions to Contextual Encoding Deficits in Schizophrenia

Abstract

1. Context The “AX”-version of the visual continuous performance task (AX-CPT) is widely used for investigating visual working memory dysfunction in schizophrenia. Event-related potentials (ERP) provide an objective index of brain function, and can be used to evaluate brain substrates underlying impaired cognition in schizophrenia. 2. Objective To assess mechanisms underlying visual working memory dysfunction in schizophrenia relative to impairment of early visual processing. 3. Design, Setting and Participants Between-group design in a chronic treatment setting, with 30 individuals with schizophrenia and 17 healthy comparison subjects. Three versions of AX-CPT, with parametric variations of the proportions of trial types, were used to test performance and underlying neural activity under differential challenge situations. Contrast sensitivity measures were obtained from the majority of subjects. 7. Main Outcome Measures Behavioral performance was assessed using d’-context scores. Integrity of stimulus- and task-related cortical activation to both cue and probe stimuli was assessed using sensory (C1, P1, N1) and cognitive (N2, CNV) ERP components. Early magnocellular/parvocellular function was assessed using contrast sensitivity. Linear regression and path analyses were used to assess relations between physiological and behavioral parameters. 8. Results Patients showed reduced amplitude of both early sensory (P1, N1) and later cognitive (N2, CNV) ERP components. Deficits in sensory (N1) and cognitive (N2) components to cue stimuli contributed independently to impaired behavioral performance. In addition, sensory deficits predicted impaired cognitive ERP generation. Finally, deficits in performance correlated with impairments in contrast sensitivity to low, but not high, spatial frequency stimuli. 9. Conclusions Working memory deficits in schizophrenia have increasingly been attributed to impairments in stimulus encoding, rather than to failures in memory retention. The present study provides objective physiological support for encoding hypotheses. Further, deficits in sensory processing contribute significantly to impaired working memory performance, consistent with generalized neurochemical models of schizophrenia.

Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia

“…37 Over recent years, deficits in magnocellular function have been confirmed in schizophrenia using psychophysical-, neurophysiological-, and functional imaging-based approaches. [38][39][40][41] Finally, deficits in both auditory and visual processing in schizophrenia have been linked to impairments in higher order cognitive. Thus, deficits in auditory tone matching ability in schizophrenia lead to impairments in detection of tonal modulations in voice ("prosody") which, in turn, lead to impairments in auditory emotion recognition and social cognition (figure 2A) 42 (Disturbances in visual processing lead to impairments in coding of visual information, which in turn affect such processes as face emotion recognition, 43,44 perceptual closure 40 (figure 2B) or continuous performance task performance 41 ( figure 2C).…”

“…[38][39][40][41] Finally, deficits in both auditory and visual processing in schizophrenia have been linked to impairments in higher order cognitive. Thus, deficits in auditory tone matching ability in schizophrenia lead to impairments in detection of tonal modulations in voice ("prosody") which, in turn, lead to impairments in auditory emotion recognition and social cognition (figure 2A) 42 (Disturbances in visual processing lead to impairments in coding of visual information, which in turn affect such processes as face emotion recognition, 43,44 perceptual closure 40 (figure 2B) or continuous performance task performance 41 ( figure 2C). Most recently, ketamine-induced reductions in a visual oddball task was associated primarily with activation reductions in sensory, as opposed to frontal, brain regions, 45 suggesting that many deficits that have been attributed to Fig.…”

“…In the auditory system, structural and functional disturbances at the level of primary auditory cortex correlate with impairments in higher auditory auditory function such as auditory emotion recognition 73 (A). In the visual system, deficits in early visual activation lead to impairments in frontal activation during tasks such as perceptual closure 40 (B) or AX-type continuous performance task (C) 41 performance.…”

Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia

“…Indeed, insufficient suppression of DMN activity during task engagement may independently contribute to cognitive deficits in schizophrenia beyond dysfunction of task-specific substrates (Anticevic et al, 2012). Given that the posterior cortical slope difference findings extend well into extrastriatal regions of the occipital cortices, an alternative or additional explanation to DMN dysfunction may be that the altered LFO-cognition relationships observed relate to early sensory processing deficits that have been described in schizophrenia and shown to contribute to higher-order cognitive impairments (Dias et al, 2011).…”

Disturbed theta and gamma coupling as a potential mechanism for visuospatial working memory dysfunction in people with schizophrenia

“…PSZ have been found to demonstrate deficits in ERPs elicited from WM tasks [17][18][19] and tasks probing sustained attention [20][21][22][23][24], among others; similar deficits have been observed in first-degree relatives of people with the disorder [22,25,26]. More recently, EEG research has examined oscillatory activity in the brain associated with WM.…”