When do contrast sensitivity deficits (or enhancements) depend on spatial frequency? Two ways to avoid spurious interactions.

Studies across a broad range of disciplines-from psychiatry to cognitive science to behavioural neuroscience-have reported on whether the magnitude of contrast sensitivity alterations in one group or condition varies with spatial frequency. Significant interactions have often gone unexplained or have been used to argue for impairments in specific processing streams. Here, we show that interactions with spatial frequency may need to be re-evaluated if the inherent skew/heteroscedasticity was not taken into account or if visual acuity could plausibly differ across groups or conditions. By re-analysing a publicly available data set, we show that-when using raw contrast sensitivity data-schizophrenia patients exhibit an apparent contrast sensitivity impairment that lessens with spatial frequency, but that when using log-transformed data or when using generalized estimating equations, this interaction reversed. The reversed interaction, but not the overall contrast sensitivity deficit, disappeared when groups were matched on visual acuity. An analysis of the contrast threshold data yielded similar results. A caveat is that matching groups on acuity is probably only defensible if acuity differences arise from non-neural factors such as optical blur. Taken together, these analyses reconcile seemingly discrepant findings in the literature and demonstrate that reporting contrast sensitivity interactions with spatial frequency requires properly accounting for visual acuity and skew/heteroscedasticity.

Frequency-domain analysis of transient visual evoked potentials in schizophrenia.

PURPOSE: Frequency-domain measures were applied to characterize neural deficits in individuals with schizophrenia using transient visual evoked potentials (tVEP). These measures were compared with conventional time-domain measures to elucidate underlying neurophysiological mechanisms and examine the value of frequency analysis. METHODS: Four frequency bands of activity identified in previous work were explored with respect to magnitude (spectral power), timing (phase), a combined measure, magnitude-squared coherence (MSC), and compared to amplitudes and times of prominent deflections in the response. RESULTS: Band 2 power/MSC (14-28 Hz) captured the major deflections in the waveform and its power predicted N75-P100 amplitude for patients and controls. Band 3 power/MSC (30-40 Hz) correlated highly with the earliest deflection (P60-N75), reflecting input to primary visual cortex (V1) and produced the largest magnitude effect. Phase of the 24th harmonic component predicted P100 peak time for patients and controls and yielded the largest group difference. Cluster analyses including time- and frequency-domain measures identified subgroups of patients with differential neurophysiological effects. A small but significant difference in visual acuity was found between groups that appears to be neurally based: Acuity (range 0.63-1.6) was not correlated with any tVEP measures in controls nor with input timing to V1 (P60 peak time) in patients, but was correlated with later tVEP measures in patients. All but two of the patients were on antipsychotic medication: Medication level (chlorpromazine equivalents) was correlated negatively with tVEP time measures and positively with certain magnitude measures yielding responses similar to controls at high levels. CONCLUSIONS: Overall, frequency-domain measures were shown to be objective and recommended as an alternative to conventional, subjective time-domain measures for analyzing tVEPs and in distinguishing between groups (patients vs. controls and patient subgroups). The findings implicated a loss of excitatory input to V1 in schizophrenia. Acuity as measured in the current study reflected disease status, and medication level was associated with improved tVEP responses. These novel tVEP techniques may be useful in revealing neurophysiological processes affected in schizophrenia and as a clinical tool.

Validation of an Intensive Care Unit Data Mart for Research and Quality Improvement.

Data derived from the electronic health record (EHR) is frequently extracted using undefined approaches that may affect the accuracy of collected variables. Further, efforts to assess data accuracy often suffer from limited collaboration between clinicians and data analysts who perform the extraction. In this manuscript, we describe the methodology behind creation of a structured, rigorously derived intensive care unit (ICU) data mart based on data automatically and routinely derived from the EHR. This ICU data mart includes high-quality data elements commonly used for quality improvement and research purposes. These data elements were identified by physicians working closely with data analysts to iteratively develop and refine algorithmic definitions for complex outcomes and risk factors. We contend that this methodology can be reproduced and applied across other institution or to other clinical domains to create high quality data marts, inclusive of complex outcomes data.

Contrast sensitivity deficits in schizophrenia: A psychophysical investigation.

Individuals with schizophrenia have problems with visual contrast processing. The current study investigated contrast sensitivity (CS) in schizophrenia/schizoaffective disorder to elucidate the underlying neural mechanisms affected by this disorder and to identify critical testing conditions that distinguish individuals with the disorder from healthy individuals. Principal component analysis was applied to the data (N = 143) to separate responses from distinct visual pathways. Participants were 68 patients and 75 age-similar controls. CS was obtained using a forced-choice psychophysical paradigm with grating patterns of low to high spatial frequency presented at short and long durations. Linear mixed-effects models were used to examine differences in log CS with respect to group, duration, and stimulus condition. Lower CSs were found in patients compared to controls over all stimulus conditions with the magnitude of deficits dependent on both spatial frequency and stimulus duration. Log CSs to low and high spatial frequencies loaded onto separate principal components, supporting the existence of two psychophysical mechanisms, transient and sustained. Critical conditions were identified to tap each mechanism. Visual acuity was correlated moderately with log CS to high, but not low, spatial frequencies, and deficits found for acuity and CS to moderate/high spatial frequencies (4-21 cycles/degree) appear to reflect dysfunction in the sustained mechanism. CS deficits found at the lowest spatial frequency tested (0.5 cycles/degree) appear to reflect dysfunction in the transient mechanism. Both types of CS deficits may have diagnostic value and implications for social and neurocognitive deficits in this disorder.

Contributions of low and high spatial frequency processing to impaired object recognition circuitry in schizophrenia.

Patients with schizophrenia exhibit cognitive and sensory impairment, and object recognition deficits have been linked to sensory deficits. The "frame and fill" model of object recognition posits that low spatial frequency (LSF) information rapidly reaches the prefrontal cortex (PFC) and creates a general shape of an object that feeds back to the ventral temporal cortex to assist object recognition. Visual dysfunction findings in schizophrenia suggest a preferential loss of LSF information. This study used functional magnetic resonance imaging (fMRI) and resting state functional connectivity (RSFC) to investigate the contribution of visual deficits to impaired object "framing" circuitry in schizophrenia. Participants were shown object stimuli that were intact or contained only LSF or high spatial frequency (HSF) information. For controls, fMRI revealed preferential activation to LSF information in precuneus, superior temporal, and medial and dorsolateral PFC areas, whereas patients showed a preference for HSF information or no preference. RSFC revealed a lack of connectivity between early visual areas and PFC for patients. These results demonstrate impaired processing of LSF information during object recognition in schizophrenia, with patients instead displaying increased processing of HSF information. This is consistent with findings of a preference for local over global visual information in schizophrenia.

Auditory tasks for assessment of sensory function and affective prosody in schizophrenia.

Schizophrenia patients exhibit impairments in auditory-based social cognition, indicated by deficits in detection of prosody, such as affective prosody and basic pitch perception. However, little is known about the psychometric properties of behavioral tests used to assess these functions. The goal of this paper is to characterize the properties of prosody and pitch perception tasks and to investigate whether they can be shortened. The pitch perception test evaluated is a tone-matching task developed by Javitt and colleagues (J-TMT). The prosody test evaluated is the auditory emotion recognition task developed by Juslin and Laukka (JL-AER). The sample includes 124 schizophrenia patients (SZ) and 131 healthy controls (HC). Properties, including facility and discrimination, of each item were assessed. Effects of item characteristics (e.g., emotion) were also evaluated. Shortened versions of the tests are proposed based on facility, discrimination, and/or ability of item characteristics to discriminate between patients and controls. Test-retest reliability is high for patients and controls for both the original and short forms of the J-TMT and JL-AER. Thus, the original as well as short forms of the J-TMT and JL-AER are suggested for inclusion in clinical trials of social cognitive and perceptual treatments. The development of short forms further increases the utility of these auditory tasks in clinical trials and clinical practice. The large SZ vs. HC differences reported here also highlight the profound nature of auditory deficits and a need for remediation.

Differential deficits in social versus monetary reinforcement learning in schizophrenia: Associations with facial emotion recognition.

Despite evidence that individuals with schizophrenia (SZ) have an intact desire for social relationships, they have small social networks and report high levels of loneliness. Difficulty with reinforcement learning (RL), the ability to update behavior based on feedback, may inhibit the formation and maintenance of social relationships in SZ. However, impaired RL in SZ has largely been demonstrated via monetary tasks. Thus, it remains unclear whether SZ are similarly impaired in social and monetary RL, or whether social-specific factors may further inhibit their ability to learn from social feedback. Thirty-one individuals with SZ and 31 healthy controls (HCs) participated in a RL paradigm to test hypotheses about social versus monetary RL. SZ exhibited impaired RL compared to HCs in both social and monetary tasks. Further, a Group × Task interaction demonstrated that SZ was more impaired when learning from social than monetary reinforcement, F(1, 59) = 5.99, p = .017. This differential deficit to social RL was not accounted for by reported pleasure from social feedback, which did not differ between groups. Instead, SZ had poorer emotion recognition than HCs, t(1, 60) = 4.80, p < .001, particularly for negative emotions, and controlling for this eliminated the differential social RL impairment. These results suggest the possibility that difficulty recognizing social cues, especially those indicating negative feedback, may relate to a reduced ability to learn from others' feedback. Thus, future research could elucidate whether targeting these emotion recognition difficulties in treatment could serve as a potential mechanism for improving social functioning in SZ. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Performance on a contour integration task as a function of contour shape in schizophrenia and controls.

Contour Integration (CI) is the ability to integrate elemental features into objects and is a basic visual process essential for object perception and recognition, and for functioning in visual environments. It is now well documented that people with schizophrenia (SZ), in addition to having cognitive impairments, also have several visual perceptual deficits, including in CI. Here, we retrospectively characterize the performance of both SZ and neurotypical individuals (NT) on a series of contour shapes, made up of Gabor elements, that varied in terms of closure and curvature. Participants in both groups performed a CI training task that included 7 different families of shapes (Lines, Ellipse, Blobs, Squiggles, Spiral, Circle and Letters) for up to 40 sessions. Two parameters were manipulated in the training task: Orientation Jitter (OJ, i.e., orientation deviations of individual Gabor elements from ideal for each shape) and Inducer Number (IN, i.e., number of Gabor elements defining the shape). Results show that both OJ and IN thresholds significantly differed between the groups, with higher (OJ) and lower (IN) thresholds observed in the controls. Furthermore, we found significant effects as a function of the contour shapes, with differences between groups emerging with contours that were considered more complex, e.g., due to having a higher degree of curvature (Blobs, Spiral, Letters). These data can inform future work that aims to characterize visual integration impairments in schizophrenia.

Comparison of psychophysical, electrophysiological, and fMRI assessment of visual contrast responses in patients with schizophrenia.

Perception has been identified by the NIMH-sponsored Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group as a useful domain for assessing cognitive deficits in patients with schizophrenia. Specific measures of contrast gain derived from recordings of steady-state visual evoked potentials (ssVEP) have demonstrated neural deficits within the visual pathways of patients with schizophrenia. Psychophysical measures of contrast sensitivity have also shown functional loss in these patients. In the current study, functional magnetic resonance imaging (fMRI) was used in conjunction with ssVEP and contrast sensitivity testing to elucidate the neural underpinnings of these deficits. During fMRI scanning, participants viewed 1) the same low and higher spatial frequency stimuli used in the psychophysical contrast sensitivity task, at both individual detection threshold contrast and at a high contrast; and 2) the same stimuli used in the ssVEP paradigm, which were designed to be biased toward either the magnocellular or parvocellular visual pathway. Patients showed significant impairment in contrast sensitivity at both spatial frequencies in the psychophysical task, but showed reduced occipital activation volume for low, but not higher, spatial frequency at the low and high contrasts tested in the magnet. As expected, patients exhibited selective deficits under the magnocellular-biased ssVEP condition. However, occipital lobe fMRI responses demonstrated the same general pattern for magnocellular- and parvocellular-biased stimuli across groups. These results indicate dissociation between the fMRI measures and the psychophysical/ssVEP measures. These latter measures appear to have greater value for the functional assessment of the contrast deficits explored here.

Consequences of magnocellular dysfunction on processing attended information in schizophrenia.

Schizophrenia is associated with perceptual and cognitive dysfunction including impairments in visual attention. These impairments may be related to deficits in early stages of sensory/perceptual processing, particularly within the magnocellular/dorsal visual pathway. In the present study, subjects viewed high and low spatial frequency (SF) gratings designed to test functioning of the parvocellular/magnocellular pathways, respectively. Schizophrenia patients and healthy controls attended to either the low SF (magnocellularly biased) or high SF (parvocellularly biased) gratings. Functional magnetic resonance imaging (fMRI) and recordings of event-related potentials (ERPs) were carried out during task performance. Patients were impaired at detecting low-frequency targets. ERP amplitudes to low-frequency gratings were diminished, both for the early sensory-evoked components and for the attend minus unattend difference component (the selection negativity), which is regarded as a neural index of feature-selective attention. Similarly, fMRI revealed that activity in extrastriate visual cortex was reduced in patients during attention to low, but not high, SF. In contrast, activity in frontal and parietal areas, previously implicated in the control of attention, did not differ between patients and controls. These findings suggest that impaired sensory processing of magnocellularly biased stimuli lead to impairments in the effective processing of attended stimuli, even when the attention control systems themselves are intact.

The spatial contrast sensitivity function and its neurophysiological bases.

Contrast processing is a fundamental function of the visual system, and contrast sensitivity as a function of spatial frequency (CSF) provides critical information about the integrity of the system. Here, we used a novel iPad-based instrument to collect CSFs and fitted the data with a difference of Gaussians model to investigate the neurophysiological bases of the spatial CSF. The reliability of repeat testing within and across sessions was evaluated in a sample of 22 adults for five spatial frequencies (0.41-13 cycles/degree) and two temporal durations (33 and 500 ms). Results demonstrate that the shape of the CSF, lowpass versus bandpass, depends on the temporal stimulus condition. Comparisons with previous psychophysical studies and with single-cell data from macaques and humans indicate that the major portion of the CSF, spatial frequencies >1.5 cycles/degree regardless of temporal condition, is determined by a 'sustained' mechanism (presumably parvocellular input to primary visual cortex [V1]). Contrast sensitivity to the lowest spatial frequency tested appears to be generated by a 'transient' mechanism (presumably magnocellular input to V1). The model fits support the hypothesis that the high spatial frequency limb of the CSF reflects the receptive field profile of the center mechanism of the smallest cells in the parvocellular pathway. These findings enhance the value of contrast sensitivity testing in general and increase the accessibility of this technique for use by clinicians through implementation on a commercially-available device.

Computational modeling of excitatory/inhibitory balance impairments in schizophrenia.

Deficits in glutamatergic function are well established in schizophrenia (SZ) as reflected in "input" dysfunction across sensory systems. By contrast, less is known about contributions of the GABAergic system to impairments in excitatory/inhibitory balance. We investigated this issue by measuring contrast thresholds for orientation detection, orientation discriminability, and orientation-tilt-aftereffect curves in schizophrenia subjects and matched controls. These measures depend on the amplitude and width of underlying orientation tuning curves, which, in turn, depend on excitatory and inhibitory interactions. By simulating a well-established V1 orientation selectivity model and its link to perception, we demonstrate that reduced cortical excitation and inhibition are both necessary to explain our psychophysical data. Reductions in GABAergic feedback may represent a compensatory response to impaired glutamatergic input in SZ, or a separate pathophysiological event. We also found evidence for the widely accepted, but rarely tested, inverse relationship between orientation discriminability and tuning width.

Cognitive function mediates the relationship between visual contrast sensitivity and functional outcome in schizophrenia.

BACKGROUND: Individuals with schizophrenia exhibit deficits in visual contrast processing, though less is known about how these deficits impact neurocognition and functional outcomes. This study investigated effects of contrast sensitivity (CS) on cognition and capacity for independent living in schizophrenia. METHODS: Participants were 58 patients with schizophrenia (n = 49) and schizoaffective disorder (n = 9). Patients completed a psychophysical paradigm to obtain CS with stimuli consisting of grating patterns of low (0.5 and 1 cycles/degree) and high spatial frequencies (4, 7, 21 cycles/degree). Patients completed the MATRICS Consensus Cognitive Battery and Wechsler Adult Intelligence Scales, Third Edition to assess cognition, and the problem-solving factor of the Independent Living Scales to assess functional capacity. We computed bivariate correlation coefficients for all pairs of variables and tested mediation models with CS to low (CS-LSF) and high spatial frequencies (CS-HSF) as predictors, cognitive measures as mediators, and capacity for independent living as an outcome. RESULTS: Cognition mediated the relationship between CS and independent living with CS-LSF a stronger predictor than CS-HSF. Mediation effects were strongest for perceptual organization and memory-related domains. In an expanded moderated mediation model, CS-HSF was found to be a significant predictor of independent living through perceptual organization as a mediator and CS-LSF as a moderator of this relationship. CONCLUSION: CS relates to functional capacity in schizophrenia through neurocognition. These relationships may inform novel visual remediation interventions.

Comparison of Scalp ERP to Faces in Macaques and Humans.

Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.

Visual processing and BDNF levels in first-episode schizophrenia.

Previous studies have shown that patients diagnosed with schizophrenia (SCZ) have deficits in early visual processing, namely contrast processing. The brain-derived neurotropic factor (BDNF) is an important measure to investigate neuroplasticity in some visual functions like visual perception. In this study, we investigated the relationship between visual processing and BDNF levels in first-episode SCZ patients. Thirty-nine healthy controls and 43 first-episode SCZ patients were enrolled. Contrast sensitivity measurements were conducted using low, mid- and high spatial frequencies. First-episode SCZ patients had higher contrast sensitivity than healthy controls for all frequencies, except for the middle spatial frequency. Negative correlations were found between BDNF, contrast sensitivity and clinical variables, mostly for middle and high spatial frequencies among females. Our results provide support for (i) the association of SCZ with alterations of magno- and parvocellular pathway functioning and (ii) decreased BDNF levels in first-episode SCZ patients. This study highlights the importance of using biomarkers along with other measures to investigate visual processing in SCZ and other disorders.

Neurophysiological, Oculomotor, and Computational Modeling of Impaired Reading Ability in Schizophrenia.

Schizophrenia (Sz) is associated with deficits in fluent reading ability that compromise functional outcomes. Here, we utilize a combined eye-tracking, neurophysiological, and computational modeling approach to analyze underlying visual and oculomotor processes. Subjects included 26 Sz patients (SzP) and 26 healthy controls. Eye-tracking and electroencephalography data were acquired continuously during the reading of passages from the Gray Oral Reading Tests reading battery, permitting between-group evaluation of both oculomotor activity and fixation-related potentials (FRP). Schizophrenia patients showed a marked increase in time required per word (d = 1.3, P < .0001), reflecting both a moderate increase in fixation duration (d = .7, P = .026) and a large increase in the total saccade number (d = 1.6, P < .0001). Simulation models that incorporated alterations in both lower-level visual and oculomotor function as well as higher-level lexical processing performed better than models that assumed either deficit-type alone. In neurophysiological analyses, amplitude of the fixation-related P1 potential (P1f) was significantly reduced in SzP (d = .66, P = .013), reflecting reduced phase reset of ongoing theta-alpha band activity (d = .74, P = .019). In turn, P1f deficits significantly predicted increased saccade number both across groups (P = .017) and within SzP alone (P = .042). Computational and neurophysiological methods provide increasingly important approaches for investigating sensory contributions to impaired cognition during naturalistic processing in Sz. Here, we demonstrate deficits in reading rate that reflect both sensory/oculomotor- and semantic-level impairments and that manifest, respectively, as alterations in saccade number and fixation duration. Impaired P1f generation reflects impaired fixation-related reset of ongoing brain rhythms and suggests inefficient information processing within the early visual system as a basis for oculomotor dyscontrol during fluent reading in Sz.

Short-term effects of nicotine gum on facial detection in healthy nonsmokers: a pilot randomized controlled trial.

Objective: The main purpose of this study was to investigate short-term effects of nicotine gum on facial detection. Methods: Fourteen participants (mean age = 26.8 years, SD = 2.5 years; eight males) were enrolled in this pilot randomized controlled trial of nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants were instructed to detect the location of a face when it was presented in a face/nonface pair on the screen. A repeated multivariate analysis of variance was conducted to analyze the results for reaction time and discrimination index. Demographics were used to explore significant association on facial detection. Bayesian analyses were also carried out considering maximum robustness to avoid bias. Results: The results indicated that the 2-mg dose resulted in faster reaction time and better discrimination than the 4-mg dose (p < 0.001). The 4-mg dose resulted in slower reaction time and lower discrimination index compared to both placebo (p < 0.01) and 2-mg doses (p < 0.001). Demographic data were not related to the outcomes. Conclusions: The results indicate that nicotine improved facial detection, but only at low doses (i.e., 2-mg), following a U-shaped curve. We trust future studies will continue to advance this research field, and if further work supports these preliminary findings, nicotine can act as therapeutic target in populations such as those with low vision.

Grant Report on Social Reward Learning in Schizophrenia †.

We report on the ongoing R21 project "Social Reward Learning in Schizophrenia". Impairments in social cognition are a hallmark of schizophrenia. However, little work has been done on social reward learning deficits in schizophrenia. The overall goal of the project is to assess social reward learning in schizophrenia. A probabilistic reward learning (PRL) task is being used in the MRI scanner to evaluate reward learning to negative and positive social feedback. Monetary reward learning is used as a comparison to assess specificity. Behavioral outcomes and brain areas, included those involved in reward, are assessed in patients with schizophrenia or schizoaffective disorder and controls. It is also critical to determine whether decreased expected value (EV) of social stimuli and/or reward prediction error (RPE) learning underlie social reward learning deficits to inform potential treatment pathways. Our central hypothesis is that the pattern of social learning deficits is an extension of a more general reward learning impairment in schizophrenia and that social reward learning deficits critically contribute to deficits in social motivation and pleasure. We hypothesize that people with schizophrenia will show impaired behavioral social reward learning compared to controls, as well as decreased ventromedial prefrontal cortex (vmPFC) EV signaling at time of choice and decreased striatal RPE signaling at time of outcome, with potentially greater impairment to positive than negative feedback. The grant is in its second year. It is hoped that this innovative approach may lead to novel and more targeted treatment approaches for social cognitive impairments, using cognitive remediation and/or brain stimulation.

Optical coherence tomography of the retina in schizophrenia: Inter-device agreement and relations with perceptual function.

BACKGROUND: Optical coherence tomography (OCT) studies have demonstrated differences between people with schizophrenia and controls. Many questions remain including the agreement between scanners. The current study seeks to determine inter-device agreement of OCT data in schizophrenia compared to controls and to explore the relations between OCT and visual function measures. METHODS: Participants in this pilot study were 12 individuals with schizophrenia spectrum disorders and 12 age- and sex-matched controls. Spectralis and Cirrus OCT machines were used to obtain retinal nerve fiber layer (RNFL) thickness and macular volume. Cirrus was used to obtain ganglion cell layer + inner plexiform layer (GCL + IPL) thickness. Visual function was assessed with low-contrast visual acuity and the King-Devick test of rapid number naming. RESULTS: There was excellent relative agreement in OCT measurements between the two machines, but poor absolute agreement, for both patients and controls. On both machines, people with schizophrenia showed decreased macular volume but no difference in RNFL thickness compared to controls. No between-group difference in GCL + IPL thickness was found on Cirrus. Controls showed significant associations between King-Devick performance and RNFL thickness and macular volume, and between low-contrast visual acuity and GCL + IPL thickness. Patients did not show significant associations between OCT measurements and visual function. CONCLUSIONS: Good relative agreement suggests that the offset between machines remains constant and should not affect comparisons between groups. Decreased macular volume in individuals with schizophrenia on both machines supports findings of prior studies and provides further evidence that similar results may be found irrespective of OCT device.