Faculty Bibliography

BACKGROUND AND HYPOTHESIS/OBJECTIVE:Individuals with schizophrenia (SZ) have well-documented behavioral and neural deficits to reinforcement learning (RL) from monetary feedback. Although they have a range of social functioning deficits, limited research has examined neural processes related to learning from social feedback. The present study examined how neural activation to social RL in SZ compares to activation to monetary RL. STUDY DESIGN/METHODS:Thirty participants with SZ and 31 healthy controls completed a Probabilistic RL paradigm that included both social and monetary RL tasks in the scanner, each with positively and negatively valenced trials. Analyses included a region of interest-based approach to examine activation in areas associated with reward, learning, and social processes and assessed neural activation when making task choices (Choice) and upon feedback receipt (Outcome) for social versus monetary RL. STUDY RESULTS/RESULTS:Results indicated that across tasks, SZ had reduced signal in regions such as caudate and orbitofrontal cortex during Choice but not Outcome. In addition, patterns of neural activation were similar during social and monetary RL, for both valences, and brain activation during RL was largely unrelated to behavioral RL performance in either group. CONCLUSIONS:Overall, the findings indicate that although SZ appear to have intact brain activation when receiving feedback about their choices, they may struggle to recruit the necessary circuitry in regions associated with generating expected values to successfully modulate their choices based on the received feedback. This aligns with literature on monetary RL in SZ and suggests that activation patterns may be similar during social RL.

BACKGROUND/UNASSIGNED:Schizophrenia (Sz) and autism spectrum disorder (ASD) are associated with reduced accuracy offace emotion recognition (FER). Nevertheless, the underlying pathophysiological mechanisms may diverge, potentially related to differential processing patterns within the early visual system. Here, we investigated physiological-level responses to emotional faces. We hypothesized that Sz and ASD would be associated with convergent behavioral performance, but divergent pathophysiological mechanisms. STUDY DESIGN/UNASSIGNED:Simultaneous eye-tracking and continuous EEG data were obtained from 23 adults diagnosed with schizophrenia (Sz), 21 autistic adults, and 24 neurotypical controls (NC) in response to intact and chimeric emotion faces. Event-related potentials (ERP) were calculated from the ongoing EEG data using time- and time-frequency (TF) domain approaches. Symptoms were rated using the Positive and Negative Symptom Scale (PANSS) and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) in Sz and ASD, respectively. STUDY RESULTS/UNASSIGNED:As predicted, Sz and ASD were associated with similar levels of reduced FER accuracy relative to NC, but differential patterns of eye tracking and EEG-related activity. Rates of eye- vs. mouth-fixations were reduced across groups but did not correlate with FER. Nevertheless, the ability to utilize eye-information diverged across groups. Thus, when viewing chimeric faces, Sz was associated with reduced tendency to utilize eye information and increased tendency to utilize mouth information even when fixation location was considered. In TF analyses, reduced FER accuracy was associated with reduced initial sensory responses in Sz, as reflected in the theta-band time-frequency response. In contrast, in ASD, reduced FER accuracy was associated with increased alpha-frequency event-related desynchronization (alpha-ERD) consistent with hyper-engagement of secondary visual regions (V2). A combination of physiological and eye-tracking measures differentiated schizophrenia and ASD with >90% accuracy. V2 hyper-engagement in ASD correlated with both reduced FER accuracy and ADOS Social Interaction domain scores. CONCLUSION/UNASSIGNED:Schizophrenia and ASD are associated with divergent physiological-level alterations within the early visual system during emotional face processing, supporting models of magnocellular visual hypoactivity in schizophrenia but retinotectal visual hyperactivity leading to hyper-engagement of non-face regions (V2) by face stimuli in ASD. These alterations, in turn, may serve as targets for future intervention studies related to social cognition.

Schizophrenia is often referred to as a cognitive disorder. A deeper and broader view of the syndrome is emerging, however, based on increasing appreciation of its associated visual system changes, including alterations in retinal neural and vascular structure and function, alterations in occipital lobe morphology and function, and their relationships with neuroinflammation and cardiometabolic factors. These and other data suggest that schizophrenia is best conceptualized as a multisystem condition. Here, we emphasize that early visual system changes in schizophrenia provide a window to the brain and to the rest of the body and provide valuable biomarkers for understanding pathophysiology and predicting multiple relevant outcomes, including the onset of a first psychotic episode, long-term course, and cognitive decline. The usefulness of early visual system markers of brain and physical health has already been demonstrated in neurodevelopmental and neurodegenerative disorders. They have particularly strong potential applicability for schizophrenia, given its progressive neurodevelopmental characteristics.

BACKGROUND:Atypical perception of visual illusions is well-documented in schizophrenia (SZ) and thought to be a consequence of impairments in visual processes including perceptual organization (PO). The Ebbinghaus illusion, in which a circle appears larger or smaller depending on the size of surrounding circles, is facilitated by PO, and the extent to which the surrounds (i.e., context) influence perception of the center circle can be considered an index of context sensitivity. In the present study, as part of a broader investigation of the impact of a novel visual remediation (VR) program for people with SZ, the Ebbinghaus illusion was used to explore the effects of VR on context sensitivity. METHODS:Participants with SZ (n = 47) were randomly assigned to one of four conditions: VR only, an active control condition (AC), or one of two conditions combining VR and AC. At three assessment points, participants completed a size comparison task based on the Ebbinghaus illusion. Context sensitivity was compared between training groups and with baseline clinical characteristics. RESULTS:At baseline, participants were strongly context sensitive. After training, participants in the VR group, but not the AC-only group, became less influenced by context. The main effect of training group and the group × time interaction terms were not significant. Participants who were less symptomatic at baseline showed the greatest reductions in context sensitivity over time. CONCLUSIONS:These findings suggest that an adaptive reduction in the influence of irrelevant context is a potential effect of VR and may reflect improved attentional focus.

This study investigated relations between a measure of early-stage visual function and self-reported visual anomalies in individuals at clinical high risk for psychosis (CHR-P). Eleven individuals at CHR identified via the Structured Interview for Psychosis-Risk Syndromes (SIPS) were recruited from a CHR-P research program in NYC. The sample was ~36% female, ranging from 16 to 33 years old (M = 23.90, SD = 6.14). Participants completed a contrast sensitivity task on an iPad with five spatial frequencies (0.41-13 cycles/degree) and completed the self-report Audio-Visual Abnormalities Questionnaire. Higher contrast sensitivity (better performance) to low spatial frequencies was associated with higher perceptual (r = 0.616, p = 0.044) and visual disturbances (r = 0.667, p = 0.025); lower contrast sensitivity to a middle spatial frequency was also associated with higher perceptual (r = -0.604, p = 0.049) and visual disturbances (r = -0.606, p = 0.048). This relation between the questionnaire and contrast sensitivity to low spatial frequency may be indicative of a reduction in lateral inhibition and "flooding" of environmental stimuli. The association with middle spatial frequencies, which play a critical role in face processing, may result in a range of perceptual abnormalities. These findings demonstrate that self-reported perceptual anomalies occur in these individuals and are linked to performance on a measure of early visual processing.

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 socialspecific 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.

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.

PURPOSE/OBJECTIVE: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.

Studies across a broad range of disciplines-from psychiatry to cognitive science to behavioral 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-analyzing a publicly available data set, we show that-when using raw contrast sensitivity data-schizophrenia patients exhibit an apparent contrast sensitivity impairment at low, but not high, spatial frequencies, 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, would disappear if 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.

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.