Structural white matter abnormalities in Schizophrenia and associations with neurocognitive performance and symptom severity.

Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age±SD=39.02±11.82; 105 males) and healthy controls (HC; n=143, mean age±SD=37.07±10.84; 102 males) were collected as part of the Function Biomedical Informatics Research Network Phase 3 study. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were compared between individuals with schizophrenia and healthy controls, and their relationships with neurocognitive performance and symptomatology assessed. Individuals with SZ had significantly lower FA in forceps minor and the left inferior fronto-occipital fasciculus compared to HC. FA in several tracts were associated with speed of processing and attention/vigilance and the severity of the negative symptom alogia. This study suggests that regional WM abnormalities are fundamentally involved in the pathophysiology of schizophrenia and may contribute to cognitive performance deficits and symptom expression observed in schizophrenia.

Orientation and contrast deviance examined: Contrast effects mimic deviant-related negativity yet neither produce the canonical neural correlate of prediction error.

The visual mismatch negativity (vMMN) is a negative-going event-related potential (ERP) component that is largest somewhere between 100 and 300 ms after the onset of an unpredictable visual event (i.e., a deviant) in an otherwise predictable sequence of visual events (i.e., standards). Many have argued that the vMMN allows us to monitor our ever-changing visual environment for deviants critical to our survival. Recently, however, it has become unclear whether unpredicted changes in low-level features of visual input, like orientation, can evoke the vMMN. I address this by testing isolated orientation changes, to confirm recent findings, and isolated contrast changes, to determine whether other low-level features of visual input do not evoke the vMMN in a traditional oddball paradigm. Eighteen participants saw sequences of rare, unanticipated, and different deviant stimuli, interspersed among frequent, anticipated, and identical standard stimuli. Stimuli were Gabor patches. Neither deviant produced a vMMN. Therefore, changes in low-level visual properties of well-controlled stimuli-a stimulus in which one property can be manipulated while all others remain unaffected-like Gabor patches do not yield a vMMN.

Auditory oddball hypoactivation in schizophrenia.

Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study compares individuals with SZ to healthy volunteers (HVs) using two cross-sectional data sets from multi-center brain imaging studies. It examines brain activation to auditory oddball targets, and their associations with cognitive domain performance, schizophrenia polygenic risk scores (PRS), and genetic variation (loci). Both sample 1 (137 SZ vs. 147 HV) and sample 2 (91 SZ vs. 98 HV), showed hypoactivation in SZ in the left-frontal pole, and right frontal orbital, frontal pole, paracingulate, intracalcarine, precuneus, supramarginal and hippocampal cortices, and right thalamus. In SZ, precuneus activity was positively related to cognitive performance. Schizophrenia PRS showed a negative correlation with brain activity in the right-supramarginal cortex. GWA analyses revealed significant single-nucleotide polymorphisms associated with right-supramarginal gyrus activity. RPL36 also predicted right-supramarginal gyrus activity. In addition to replicating hypoactivation for oddball targets in SZ, this study identifies novel relationships between regional activity, cognitive performance, and genetic loci that warrant replication, emphasizing the need for continued data sharing and collaborative efforts.

Attention is required for canonical brain signature of prediction error despite early encoding of the stimuli.

Prediction error is a basic component of predictive-coding theory of brain processing. According to the theory, each stage of brain processing of sensory information generates a model of the current sensory input; subsequent input is compared against the model and only if there is a mismatch, a prediction error, is further processing performed. Recently, Smout and colleagues found that a signature of prediction error, the visual (v) mismatch negativity (MMN), for a fundamental property of visual input-its orientation-was absent without endogenous attention on the stimuli. This is remarkable because the weight of evidence for MMNs from audition and vision is that they occur without endogenous attention. To resolve this discrepancy, we conducted an experiment addressing 2 alternative explanations for Smout and colleagues' finding: that it was from a lack of reproducibility or that participants' visual systems did not encode the stimuli when attention was on something else. We conducted a similar experiment to that of Smout and colleagues. We showed 21 participants sequences of identically oriented Gabor patches, standards, and, unpredictably, otherwise identical, Gabor patches differing in orientation by ±15°, ±30°, and ±60°, deviants. To test whether participants encoded the orientation of the standards, we varied the number of standards preceding a deviant, allowing us to search for a decrease in activity with the number of repetitions of standards-repetition suppression. We diverted participants' attention from the oriented stimuli with a central, letter-detection task. We reproduced Smout and colleagues' finding of no vMMN without endogenous attention, strengthening their finding. We found that our participants showed repetition suppression: They did encode the stimuli preattentively. We also found early processing of deviants. We discuss various explanations why the earlier processing did not extend into the vMMN time window, including low precision of prediction.

Five negative symptom domains are differentially associated with resting state amplitude of low frequency fluctuations in Schizophrenia.

This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need in schizophrenia.

An ERP study of hemispheric differences in perceptual representations of language reveals meaning attribution in the right hemisphere and constituents of the N400-effect.

Recent findings have revealed that the right hemisphere (RH) is uniquely involved in integrating perceptual information from linguistic input to simulate a mental model of that input. We extend on these findings by testing whether meaning is generated from such models. Participants (N = 37) heard auditory passages describing the visuospatial arrangement of elements into a perceptual representation of a familiar object, then judged whether a laterally-presented target word matched the object. We found a central N400-effect for left visual-field targets, suggesting that meaning was also accessible to the RH. There was no statistical difference for right visual-field targets. Principle component analysis of the data revealed that the N400-effect was driven by positive components. Consequently, the results suggest that i) RH contributions to language comprehension include integrative and perceptual processes that enable overall meaning to be generated from representations of discourse, and ii) positive ERP components may produce N400-effects.

Perceptual elaboration paradigm (PEP): A new approach for investigating mental representations of language.

To examine hemispheric differences in accessing a mental representation that embodies perceptual elements and their spatial relationships (i.e., perceptual elaboration and integration), we developed a cross-modal perceptual elaboration paradigm (PEP) in which an imagined percept, rather than a propositional concept, determined congruency. Three target image conditions allow researchers to test which mental representation is primarily accessed when the target is laterally presented. For example, the "Integrated" condition is congruent with either propositional or perceptual mental representations; therefore, results from both hemifield conditions (RVF/LH vs. LVF/RH) should be comparable. Similarly, the "Unrelated" condition is incongruent with either propositional or perceptual mental representations; therefore, results from both hemifield conditions should be comparable as well. However, the "Unintegrated" condition is congruent with the propositional mental representation but not the perceptual mental representation. Should either hemisphere access one representation initially, differences will be revealed in either behavioural or electroencephalography results. This paradigm:•is distinct from existing paired paradigms that emphasize semantic associations.•is important given increasing evidence that discourse comprehension involves accessing perceptual information.•allows researchers to examine the extent to which a mental representation of discourse can embody perceptual elaboration and integration.

The quest for the genuine visual mismatch negativity (vMMN): Event-related potential indications of deviance detection for low-level visual features.

Research shows that the visual system monitors the environment for changes. For example, a left-tilted bar, a deviant, that appears after several presentations of a right-tilted bar, standards, elicits a classic visual mismatch negativity (vMMN): greater negativity for deviants than standards in event-related potentials (ERPs) between 100 and 300 ms after onset of the deviant. The classic vMMN is contributed to by adaptation; it can be distinguished from the genuine vMMN that, through use of control conditions, compares standards and deviants that are equally adapted and physically identical. To determine whether the vMMN follows similar principles to the auditory mismatch negativity (MMN), in two experiments we searched for a genuine vMMN from simple, physiologically plausible stimuli that change in fundamental dimensions: orientation, contrast, phase, and spatial frequency. We carefully controlled for attention and eye movements. We found no evidence for the genuine vMMN, despite adequate statistical power. We conclude that either the genuine vMMN is a rather unstable phenomenon that depends on still-to-be-identified experimental parameters, or it is confined to visual stimuli for which monitoring across time is more natural than monitoring over space, such as for high-level features. We also observed an early deviant-related positivity that we propose might reflect earlier predictive processing.

Hemispheric differences in perceptual integration during language comprehension: An ERP study.

The left hemisphere (LH) is responsible for many fundamental aspects of language; however, converging evidence suggests the right hemisphere (RH) is critically involved in higher-level language comprehension. We examined the extent of each hemispheres' access to a meaningful mental representation of language by recording electroencephalography while participants (N = 44) completed a computer-based task where auditory sentences described individual elements of an image. If integrated successfully, this allowed the construction of a meaningful mental representation. If unsuccessful, the individual elements were in themselves meaningless. Participants saw a lateralised image that was either an integrated representation of the object described in the previous auditory passage ("integrated"), an unintegrated representation of each of the individual elements ("unintegrated"), or an integrated representation of an object that did not match the previous passage ("unrelated"). Evidenced by the trend in N300 amplitudes, we found that both hemispheres accessed a mental representation that embodied the elements described in the preceding passage. However, only the RH distinguished integrated versus unintegrated targets, suggesting that the RH accessed a mental representation that embodied the correct spatial relationships between elements (i.e., perceptual integration) as well as the individual imagined elements (i.e., perceptual elaboration). These results provide evidence of a clear RH contribution to the integration of perceptual information during language comprehension.