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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.

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.

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 mal...

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.

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.

Our main purpose was to investigate how smoking and nicotine interacted with specific aspects of cognitive functioning. The research was conducted in two parts: (i) an investigation of cognition in heavy smokers and healthy nonsmokers, and (ii) an investigation of cognition in healthy nonsmokers enrolled in a clinical trial involving administration of nicotine gum. Results indicated that the relationship between smoking and nicotine was characterized by an inverted U-shaped effect. On the one hand, cognitive test performance of the heavy smokers group was reduced on all of the cognitive tasks used here. On the other hand, healthy nonsmokers who used 2-mg of nicotine gum performed better, whilst the 4-mg group performed worse than the 2-mg and the placebo group. Demographic data were not related to the cognitive tasks. These data suggest that small doses of nicotine can have an activating function that leads to improved cognition, while heavy smoking on a chronic (and possibly acute) basis leads to cognitive impairment.

A reduced P1 visual-evoked potential amplitude has been reported across several psychiatric disorders, including schizophrenia-spectrum, bipolar, and depressive disorders. In addition, a difference in P1 amplitude change to a red background compared to its opponent color, green, has been found in schizophrenia-spectrum samples. The current study examined whether specific psychiatric symptoms that related to these P1 abnormalities in earlier studies would be replicated when using a broad transdiagnostic sample. The final sample consisted of 135 participants: 26 with bipolar disorders, 25 with schizophrenia-spectrum disorders, 19 with unipolar depression, 62 with no current psychiatric disorder, and 3 with disorders in other categories. Low (8%) and high (64%) contrast check arrays were presented on gray, green, and red background conditions during electroencephalogram, while an eye tracker monitored visual fixation on the stimuli. Linear regressions across the entire sample (N = 135) found that greater severity of both clinician-rated and self-reported delusions/magical thinking correlated with a reduced P1 amplitude on the low contrast gray (neutral) background condition. In addition, across the entire sample, higher self-reported constricted affect was associated with a larger decrease in P1 amplitude (averaged across contrast conditions) to the red, compared to green, background. All relationships remained statistically significant after covarying for diagnostic class, suggesting that they are relatively transdiagnostic in nature. These findings indicate that early visual processing abnormalities may be more directly related to specific transdiagnostic symptoms such as delusions and constricted affect rather than specific psychiatric diagnoses or broad symptom factor scales.

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.

Objective Few studies have evaluated the effects of visual remediation strategies in schizophrenia despite abundant evidence of visual-processing alterations in this condition. We report preliminary, case-study-based evidence regarding the effects of visual remediation in this population. Method We describe implementation of a visual-perceptual training program called ULTIMEYES (UE) and initial results through 3 brief case studies of individuals with schizophrenia. UE targets broad-based visual function, including low-level processes (e.g., acuity, contrast sensitivity) as well as higher level visual functions. Three inpatients, recruited from a research unit, participated in at least 38 sessions 3 to 4 times per week for approximately 25 min per session. Contrast sensitivity (a trained task), as well as acuity and perceptual organization (untrained tasks), were assessed before and after the intervention. Levels of progression through the task are also reported. Results UE was well tolerated by the participants and led to improvements in contrast sensitivity, as well as more generalized gains in visual acuity in all 3 participants and perceptual organization in 2 participants. Symptom profiles were somewhat different for each participant, but all were symptomatic during the intervention. Despite this, they were able to focus on and benefit from training. The adaptive nature of the training was well suited to the slower progression of 2 participants. Conclusions and implications for practice These case studies set the stage for further research, such as larger, randomized controlled trials of the intervention that include additional assessments of perceptual function and measures of cognition, social cognition, and functional outcomes. (PsycINFO Database Record

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.

Although social cognition deficits have been associated with schizophrenia, social trait judgments - or first impressions - have rarely been studied. These first impressions, formed immediately after looking at a person's face, have significant social consequences. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects rated 30 neutral faces on 10 positive or negative traits: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. Compared to controls, patients gave higher ratings for positive traits as well as for negative traits. Patients also demonstrated more ambivalence in their ratings. Patients who were exhibiting paranoid symptoms assigned higher intensity ratings for positive social traits than non-paranoid patients. Social trait ratings were negatively correlated with everyday problem solving skills in patients. Although patients appeared to form impressions of others in a manner similar to controls, they tended to assign higher scores for both positive and negative traits. This may help explain the social deficits observed in schizophrenia: first impressions of higher degree are harder to correct, and ambivalent attitudes may impair the motivation to interact with others. Consistent with research on paranoia and self-esteem, actively-paranoid patients' positive social traits judgments were of higher intensity than non-paranoid patients'.

PURPOSE: The goals of the study were to further assess contrast sensitivity to (1) investigate the existence of monocular vs. binocular differences; (2) observe possible differences between sample sizes; (3) investigate the effects of test–retest repeatability. METHODS: Contrast sensitivity measurements were obtained by presenting eight horizontal sine-wave gratings (ranging from 0.2 to 20 cycles per degree). A three-up-one-down method was used to obtain thresholds with a criterion of 79.4% correct responses for each spatial frequency. The mean of 12 reversals was used for obtaining thresholds, and the two-alternative forced-choice method was used. Data were recorded in 55 naive observers from 20 to 45 years. All participants were free from identifiable ocular disease and had normal visual acuity. RESULTS: We observed the absence of differences on CSF for both monocular and binocular observers, as well as the absence of differences between large sample sizes. The latter investigation revealed a high degree of repeatability across time (baseline to 6 months later) with the higher test–retest for low and high spatial frequencies. CONCLUSIONS: Our results indicated that spatial contrast sensitivity measurements were little influenced by variables, such as binocular summation, eye dominance, sample size and time using the Metropsis test. The results obtained here have significance for basic and clinical vision science.

Schizophrenia patients (SCZ) demonstrate deficits in many domains of mental functioning, including visual perception. An issue that has been relatively unexplored, in terms of explaining variation in visual function in SCZ, however, is medication use. The present study explored potential medication effects on color vision in SCZ, a process that is strongly linked to dopaminergic function in the retina. SCZ patients who had clear-cut either typical (n = 29) or atypical (n = 29) monotherapy, without any other concurrent medication, and a group of age- and gender-matched healthy controls participated in the study. Color vision was assessed by the Cambridge Colour Test, using the Trivector and Ellipse subtests. The results demonstrated impaired color perception in patients with schizophrenia, especially in those receiving typical antipsychotics, but these deficits were subtle and not generalized to all parameters. Our findings are consistent with the known neurophysiology of the retina and visual pathways, and with the effects of dopamine blocking medications, but the results should be carefully interpreted.

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.

Background Among the various cognitive and affective evaluations that contribute to decisions about whether to engage in a future activity, three affective evaluations are particularly relevant: 1) interest in the activity itself, 2) the pleasure anticipated from the activity and 3) the excitement experienced while looking forward to the activity. In addition to these pre-activity evaluations, affective evaluations that are done after the activity is completed impact people's motivation to repeat the same activity. Although extant research suggests that these affective processes may be impaired in schizophrenia, it is not clear whether these impairments are mostly secondary to cognitive deficits. Method In three independent studies utilizing simple laboratory tasks with minimal cognitive demands, patients with schizophrenia or schizoaffective disorder and healthy control subjects evaluated their pleasure, interest, and excitement immediately before and after completing the tasks. Results Patients' anticipated pleasure and posttest evaluations of pleasure and interest were significantly greater than controls'. No group differences were found for excitement. In patients, there were significant negative correlations between anticipated pleasure, pretest excitement and depression scores, and between pretest interest and negative symptoms. Conclusions In these experiments, immediate affective evaluations reported by participants with schizophrenia or schizoaffective disorder were greater or similar to controls'. This finding is consistent with recent affective research showing that experiences of pleasure are intact in schizophrenia. These results emphasize the need to disentangle affective from cognitive processes in order to better understand the complex impairments present in schizophrenia spectrum disorders.

The ability to read passages of information fluently and with comprehension is a basic component of socioeconomic success. Reading ability depends on the integrity of underlying visual and auditory (phonological) systems. This study investigated the integrity of reading ability in schizophrenia relative to the integrity of underlying visual and auditory function.The participants were 45 schizophrenia patients, 19 clinical high-risk patients, and 65 comparison subjects. Reading was assessed using tests sensitive to visual or phonological reading dysfunction. Sensory, neuropsychological, and functional outcome measures were also obtained.Schizophrenia patients displayed reading deficits that were far more severe (effect size2.0) than would be predicted based on general neurocognitive impairments (effect size 1.0-1.4). The deficits correlated highly with both visual and auditory sensory measures, including impaired mismatch negativity generation (r=0.62, N=51, p=0.0002). Patients with established schizophrenia displayed both visual and phonological impairments, whereas high-risk patients showed isolated visual impairments. More than 70% of schizophrenia patients met criteria for acquired dyslexia, with 50% reading below eighth grade level despite intact premorbid reading ability. Reading deficits also correlated significantly (rp=0.4, N=30, p=0.03) with failure to match parental socioeconomic achievement, over and above contributions of more general cognitive impairment.Patients with schizophrenia display severe deficits in reading ability that represent a potentially remediable cause of impaired socioeconomic function. Such deficits are not presently captured during routine clinical assessment. Deficits most likely develop during the years immediately surrounding illness onset and may contribute to the reduced educational and occupational achievement associated with schizophrenia.

Schizophrenia is associated with deficits in the ability to perceive emotion based on tone of voice. The basis for this deficit remains unclear, however, and relevant assessment batteries remain limited. The authors evaluated performance in schizophrenia on a novel voice emotion recognition battery with well-characterized physical features, relative to impairments in more general emotional and cognitive functioning.The authors studied a primary sample of 92 patients and 73 comparison subjects. Stimuli were characterized according to both intended emotion and acoustic features (e.g., pitch, intensity) that contributed to the emotional percept. Parallel measures of visual emotion recognition, pitch perception, general cognition, and overall outcome were obtained. More limited measures were obtained in an independent replication sample of 36 patients, 31 age-matched comparison subjects, and 188 general comparison subjects.Patients showed statistically significant large-effect-size deficits in voice emotion recognition (d=1.1) and were preferentially impaired in recognition of emotion based on pitch features but not intensity features. Emotion recognition deficits were significantly correlated with pitch perception impairments both across (r=0.56) and within (r=0.47) groups. Path analysis showed both sensory-specific and general cognitive contributions to auditory emotion recognition deficits in schizophrenia. Similar patterns of results were observed in the replication sample.The results demonstrate that patients with schizophrenia show a significant deficit in the ability to recognize emotion based on tone of voice and that this deficit is related to impairment in detecting the underlying acoustic features, such as change in pitch, required for auditory emotion recognition. This study provides tools for, and highlights the need for, greater attention to physical features of stimuli used in studying social cognition in neuropsychiatric disorders.

Background Three temporal stages in the evaluation of positive affect can be identified: anticipation, experience (hedonia) and memory. In schizophrenia, despite research indicating non-impaired hedonic capacities, little is known about anticipation and memory of positive affect. Moreover, the role of positive affect evaluations on motivation has rarely been studied in schizophrenia. Method Seventy individuals with schizophrenia and 35 non-patient control participants completed an evocative emotional task consisting of pictures and sounds. Following each presentation, participants rated their hedonic experience. Ratings of pre-test anticipated and post-test remembered pleasures were also obtained. Finally, explicit motivation to repeat the task was assessed. Results Compared to control participants, schizophrenia participants demonstrated similar levels of anticipation, hedonia and motivation, as well as significantly increased remembered pleasure. In schizophrenia, affective processes had lower correlations with motivation than in controls, and only remembered pleasure predicted motivation. Moreover, the predictive value of hedonia was significantly lower in schizophrenia. Conclusions The affective and cognitive processes involved in the anticipation, experience and memory of positive affective events showed no deficit, and to the contrary, immediately remembered pleasure was higher in schizophrenia. However, important deficits resided in the inter-connectivity between affective evaluations and motivational processes. The major deficit in schizophrenia participants' reward system was not in hedonic experiences but in the translation of pleasurable experiences into motivational states.

Deficits in visual processing are now recognized as a core feature of schizophrenia. In the 1940s, Louis Thurstone developed a series of tests designed to evaluate specific aspects of visual perceptual processing including the Closure Flexibility Test (CFT), which was designed to measure "the ability to hold a configuration in mind despite distraction." The present study evaluated patients' performance on this task and its relationship to other tests of neuropsychological function, particularly to a measure of sustained visual attention. Thirty-nine patients with schizophrenia or schizoaffective disorder and 40 controls participated. The CFT was administered both in its original form (10 min) and also in a briefer form (3 min) in which only a portion of stimuli were given. Patients showed highly significant large effect-size deficits on both the original (d=1.6) and brief (d=1.2) CFT. Between-group deficits in performance survived co-variation for IQ. In addition, the CFT score was significantly related to performance on the MATRICS measure of attention/vigilance, the Continuous Performance Test-Identical Pairs version (CPT-IP). This correlation remained significant even after controlling for non-specific intercorrelations among neurocognitive measures. Results confirm the severity of early visual processing deficits in schizophrenia. In addition, the CFT is a brief, easy to administer alphabet-independent, paper-and-pencil test with established psychometric properties that may be useful as an index of the sustained visual attention construct in schizophrenia.

Schizophrenia is associated with cognitive processing deficits, including deficits in executive processing, that represent a core component of the disorder. In the Task Switching Test, subjects view ambiguous stimuli and must alternate between competing rules to generate correct responses. Subjects show worse performance (prolonged response time and/or increased error rates) on the first response after a switch than on subsequent responses ("switch costs"), as well as performing worse when stimuli are incongruent as opposed to congruent ("congruence costs"). Finally, subjects show worse performance in the dual vs single task condition ("mixing costs"). In monkeys, the N-methyl-D-aspartate (NMDA) antagonist ketamine has been shown to increase congruence but not switch costs. Here, subjects viewed colored letters and had to respond alternately based upon letter (X vs O) or color (red vs blue). Switch, congruence and mixing costs were calculated. Patients with schizophrenia (n = 16) and controls (n = 17) showed similar switch costs, consistent with prior literature. Patients nevertheless showed increased congruence and mixing costs. In addition, relative to controls, patients showed worse performance across conditions in the letter vs color tasks, suggesting deficits in form vs color processing. Overall, while confirming executive dysfunction in schizophrenia, this study indicates that not all aspects of executive control are impaired and that the task switching paradigm may be useful for evaluating neurochemical vs neuroanatomic hypotheses of schizophrenia.

Individuals with schizophrenia show reliable deficits in the ability to recognize emotions from vocal expressions. Here, we examined emotion recognition ability in 23 schizophrenia patients relative to 17 healthy controls using a stimulus battery with well-characterized acoustic features. We further evaluated performance deficits relative to ancillary assessments of underlying pitch perception abilities. As predicted, patients showed reduced emotion recognition ability across a range of emotions, which correlated with impaired basic tone matching abilities. Emotion identification deficits were strongly related to pitch-based acoustic cues such as mean and variability of fundamental frequency. Whereas healthy subjects' performance varied as a function of the relative presence or absence of these cues, with higher cue levels leading to enhanced performance, schizophrenia patients showed significantly less variation in performance as a function of cue level. In contrast to pitch-based cues, both groups showed equivalent variation in performance as a function of intensity-based cues. Finally, patients were less able than controls to differentiate between expressions with high and low emotion intensity, and this deficit was also correlated with impaired tone matching ability. Both emotion identification and intensity rating deficits were unrelated to valence of intended emotions. Deficits in both auditory emotion identification and more basic perceptual abilities correlated with impaired functional outcome. Overall, these findings support the concept that auditory emotion identification deficits in schizophrenia reflect, at least in part, a relative inability to process critical acoustic characteristics of prosodic stimuli and that such deficits contribute to poor global outcome.

Sensory processing deficits in schizophrenia have been documented for several decades, but their underlying neurophysiological substrates are still poorly understood. In the visual system, the pattern of pathophysiology reported in several studies is suggestive of dysfunction within the magnocellular visual pathway beginning in early sensory cortex or even subcortically. The present study used functional magnetic resonance imaging to investigate further the neurophysiological bases of visual processing deficits in schizophrenia and in particular the potential role of magnocellular stream dysfunction. Sinusoidal gratings systematically varying in spatial frequency content were presented to subjects at low and high levels of contrast to differentially bias activity in magnocellular and parvocellular pathways based on well established differences in neuronal response profiles. Hemodynamic responses elicited by different spatial frequencies were mapped over the occipital lobe and then over the entire brain. Retinotopic mapping was used to localize the occipital activations with respect to the boundaries of visual areas V1 and V2, which were demarcated in each subject. Relative to control subjects, schizophrenia patients showed markedly reduced activations to low, but not high, spatial frequencies in multiple regions of the occipital, parietal, and temporal lobes. These findings support the hypothesis that schizophrenia is associated with impaired functioning of the magnocellular visual pathway and further suggest that these sensory processing deficits may contribute to higher-order cognitive deficits in working memory, executive functioning, and attention.

Much work in the cognitive neuroscience of schizophrenia has focused on attention, memory, and executive functioning. To date, less work has focused on perceptual processing. However, perceptual functions are frequently disrupted in schizophrenia, and thus this domain has been included in the CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) project. In this article, we describe the basic science presentation and the breakout group discussion on the topic of perception from the first CNTRICS meeting, held in Bethesda, Maryland on February 26 and 27, 2007. The importance of perceptual dysfunction in schizophrenia, the nature of perceptual abnormalities in this disorder, and the critical need to develop perceptual tests appropriate for future clinical trials were discussed. Although deficits are also seen in auditory, olfactory, and somatosensory processing in schizophrenia, the first CNTRICS meeting focused on visual processing deficits. Key concepts of gain control and integration in visual perception were introduced. Definitions and examples of these concepts are provided in this article. Use of visual gain control and integration fit a number of the criteria suggested by the CNTRICS committee, provide fundamental constructs for understanding the visual system in schizophrenia, and are inclusive of both lower-level and higher-level perceptual deficits.

Perceptual organization represents a basic and essential function that occurs at an intermediate level of visual processing. Much of the previous research on perceptual organization in schizophrenia employed indirect measurements, or included factors beyond sensory processing. The aims of the present study were to determine the integrity of perceptual organization in schizophrenia, as well as to determine the stimulus duration necessary to perform perceptual organization. Psychophysical measurements were compared between patients with schizophrenia and matched control subjects. Participants viewed dot patterns briefly presented on a computer monitor, and indicated whether stimuli appeared grouped as vertical or horizontal lines. Grouping was based upon either relative proximity or similarity in color. Across trials, relative proximity or color similarity was progressively reduced until stimuli became bi-stable (perceived as either of two patterns of grouping), establishing the grouping threshold. In separate conditions, stimuli were immediately followed by a mask to limit processing. Stimulus duration was progressively reduced until stimuli became bi-stable, establishing the critical stimulus duration (CSD). Schizophrenia patients demonstrated elevated grouping thresholds for grouping by proximity as well as color similarity. In addition, CSD was significantly extended for the schizophrenia group, with a nearly four-fold increase in duration of processing. These results provide direct evidence of impairment in schizophrenia for perceptual organization based upon spatial relationships and feature similarity, and suggest deficits in low-level perceptual organization processes. Although this study did not directly investigate the physiological correlates underlying perceptual impairments, these results are consistent with a theory of impaired lateral connections within visual cortical areas in schizophrenia.

Visual processing deficits are an integral component of schizophrenia and are sensitive predictors of schizophrenic decompensation in healthy adults. The primate visual system consists of discrete subcortical magnocellular and parvocellular pathways, which project preferentially to dorsal and ventral cortical streams. Subcortical systems show differential stimulus sensitivity, while cortical systems, in turn, can be differentiated using surface potential analysis. The present study examined contributions of subcortical dysfunction to cortical processing deficits using high-density event-related potentials. Event-related potentials were recorded to stimuli biased towards the magnocellular system using low-contrast isolated checks in Experiment 1 and towards the magnocellular or parvocellular system using low versus high spatial frequency (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of 23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric volunteers of similar age. In Experiment 1, a large decrease in the P1 component of the visual event-related potential in response to magnocellular-biased isolated check stimuli was seen in patients compared with controls (F = 13.2, P = 0.001). Patients also showed decreased slope of the contrast response function over the magnocellular-selective contrast range compared with controls (t = 9.2, P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F = 8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli in patients with schizophrenia, but were intact to parvocellular-biased HSF stimuli, regardless of generator location. Source waveforms derived from inverse dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to LSF stimuli in Experiment 2, consistent with surface waveforms. These results indicate pervasive magnocellular dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia.

Background.Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated.Method.The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood.Results.Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult.Conclusions.Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

Explicit but not implicit facial emotion perception has been shown to be impaired in schizophrenia. In this study, we used newly developed technology in social neuroscience to examine implicit emotion processing. It has been shown that when people look at faces, they automatically infer social traits, and these trait judgments rely heavily on facial features and subtle emotion expressions even with neutral faces. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects completed a computer task with 30 well-characterized neutral faces. They rated each face on 10 trait judgments: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. The degree to which trait ratings were predicted by objectively-measured subtle emotion expressions served as a measure of implicit emotion processing. Explicit emotion recognition was also examined. Trait ratings were significantly predicted by subtle facial emotional expressions in controls and patients. However, impairment in the implicit emotion perception of fear, happiness, anger and surprise was found in patients. Moreover, these deficits were associated with poorer everyday problem-solving skills and were relatively independent of explicit emotion recognition. Implicit emotion processing is impaired in patients with schizophrenia or schizoaffective disorder. Deficits in implicit and explicit emotion perception independently contribute to the patients' poor daily life skills. More research is needed to fully understand the role of implicit and explicit processes in the functional deficits of patients, in order to develop targeted and useful remediation interventions.

Visual processing abnormalities have been reported across a range of psychotic and mood disorders, but are typically examined within a particular disorder. The current study used a novel transdiagnostic approach to examine diagnostic classes, clinician-rated current symptoms, and self-reported personality traits in relation to visual processing abnormalities. We examined transient visual-evoked potentials (VEPs) from 48 adults (56% female), representing a wide range of psychotic and mood disorders, as well as individuals with no history of psychiatric disorder. Stimuli were low contrast check arrays presented on green and red backgrounds. Pairwise comparisons between individuals with schizophrenia-spectrum disorders (SSD), chronic mood disorders (CMD), and nonpsychiatric controls (NC) revealed no overall differences for either P1 or N1 amplitude. However, there was a significant interaction with the color background in which the NC group showed a significant increase in P1 amplitude to the red, vs. green, background, while the SSD group showed no change. This was related to an increase in social anhedonia and general negative symptoms. Stepwise regressions across the entire sample revealed that individuals with greater apathy and/or eccentric behavior had a reduced P1 amplitude. These relationships provide clues for uncovering the underlying causal pathology for these transdiagnostic symptoms.

Patients with schizophrenia show impairments in motion processing, along with deficits in lower level processing primarily involving the magnocellular visual pathway. The present study investigates potential magnocellular contributions to impaired motion processing in schizophrenia using a combined neurophysiological and behavioral approach. As compared to prior motion studies in schizophrenia, thresholds were determined for both incoherent and coherent visual motion. In this study, velocity discrimination thresholds were measured for schizophrenia patients (n = 14) and age-matched normal control subjects (n = 16) using a staircase procedure. Early visual processing was evaluated using steady-state visual evoked potentials (ssVEP), with stimuli biased toward activation of either the magnocellular or parvocellular visual pathways through luminance contrast manipulation. Patients with schizophrenia showed poor velocity discrimination for both incoherent and coherent motion, with no significant group × task interaction. Further, when coherent motion performance was measured at individually determined incoherent motion thresholds, accuracy levels for patients were similar to controls, also indicating similarity of deficit for incoherent vs. coherent motion discrimination. Impairments in velocity discrimination correlated significantly with reduced amplitude of ssVEP elicited by magnocellular – but not parvocellular – selective stimuli. This study demonstrates that deficits in motion processing in schizophrenia are significantly related to reduced activation of the magnocellular visual system. Further, this study supports and extends prior reports of impaired motion processing in schizophrenia, and indicates significant bottom-up contributions to higher-order cognitive impairments.

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.

Background Deficits in affect recognition are prominent features of schizophrenia. Within the auditory domain, patients show difficulty in interpreting vocal emotional cues based on intonation (prosody). The relationship of these symptoms to deficits in basic sensory processing has not been previously evaluated. Methods Forty-three patients and 34 healthy comparison subjects were tested on two affective prosody measures: voice emotion identification and voice emotion discrimination. Basic auditory sensory processing was measured using a tone-matching paradigm and the Distorted Tunes Test (DTT). A subset of subjects was also tested on facial affect identification and discrimination tasks. Results Patients showed significantly impaired performance on all emotion processing tasks. Within the patient group, a principal components analysis demonstrated significant intercorrelations between basic pitch perception and affective prosodic performance. In contrast, facial affect recognition deficits represented a distinct second component. Prosodic affect measures correlated significantly with severity of negative symptoms and impaired global outcome. Conclusions These results demonstrate significant relationships between basic auditory processing deficits and impaired receptive prosody in schizophrenia. The separate loading of auditory and visual affective recognition measures suggests that within-modality factors may be more significant than cross-modality factors in the etiology of affect recognition deficits in schizophrenia.

Compromised white matter (WM) integrity in inferior frontal WM has been related to impulsivity in men with schizophrenia. However, these relationships may be more widespread. Fractional anisotropy (FA) derived from diffusion tensor imaging of 25 men with schizophrenia was transformed into Talairach space. Correlations between FA and impulsiveness were examined on a voxelwise basis. We found negative correlations between FA and impulsivity in inferior frontal WM, anterior cingulate, caudate, insula, and inferior parietal lobule. Positive correlations were obtained in the left postcentral gyrus, right superior/middle temporal gyrus, and bilateral fusiform gyrus. These areas may comprise a fronto-temporo-limbic circuit that modulates impulsivity. The voxelwise correlation method can serve as a hypothesis-generation method for relating target behaviors to their underlying neural networks.

Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia.Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity.Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast.These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.

Chronic cocaine use has been shown to produce neurochemical alterations which persist after acute withdrawal. This study assessed the effects of cocaine use on the acoustic startle response and sensorimotor gating using prepulse inhibition (PPI) of startle. Nine male control subjects (mean age = 41.6) and 15 male cocaine users (mean age = 43.2) were tested, the latter after heavy cocaine use ranging from 4 to 27 years (mean age = 16.7). Cocaine users had been cocaine free for four days to six months (mean = 17 days) at testing. Cocaine users exhibited a 68% reduction in startle amplitudes (F = 7.4; df = 1,22; p < .01) compared to controls. There were trends towards increased PPI in cocaine users under certain conditions; however, there were no significant main effects. These results indicate that chronic cocaine use produces impairment of the startle response which persists after cessation of cocaine use. These findings may reflect changes in the dopaminergic system resulting from chronic cocaine use.

Patients with schizophrenia have deficits in early information processing, which have been demonstrated on several tasks, including the backward masking paradigm (Braff et al 1991). On this task, patients with schizophrenia, asked to identify a first "target" stimulus, followed by a second "masking" stimulus (a cross of Xs), need longer interstimulus intervals (ISis) between target and mask than controls to successfully identify the target stimulus (Braff et al 1991). This deficit in initial processing could lead to faulty intake of information resulting in clinical symptomatology. One recent study indicates that the backward masking deficit in patients with schizophrenia is related to thought disorder (Perry and Braff 1994). The goal of this study is to further examine potential correlates of backward masking dysfunction. First, we examined whether or not backward masking deficits are due to a medication effect. Unmedicated patients show a masking deficit (Braff and Saccuzzo 1982; Harvey et al 1990), but most studies have examined medicated patients. This pilot study is the first study to our knowledge to utilize a within-subjects design to test patients on and off medication, thus providing a more rigorous test of the

Emerging evidence indicates that schizophrenia may in some cases be a neurodevelopmental disorder, resulting in part from the effects of prenatal exposures. Studies by our group have focused attention on the potential role of prenatal nutritional deficiency as a potential etiological factor. Therefore, we sought to examine the biological plausibility of prenatal nutritional deprivation in the etiopathogenesis of schizophrenia. We conducted a review of the pertinent literature. Four lines of evidence support prenatal nutritional deficiencies as a plausible set of risk factors for schizophrenia: a) their effects are not incompatible with the epidemiology of schizophrenia; b) they have adverse effects on brain development; c) general malnutrition results in neuropathological anomalies of brain regions implicated in schizophrenia; and d) prenatal malnutrition affects maternal systems critical to the developing fetal nervous system. There is sufficient evidence to warrant further studies of prenatal nutritional deficits as risk factors for schizophrenia. A strategy for testing these hypotheses is outlined.

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.

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.

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.

We will review evidence from preclinical literature that prenatal nutritional deprivation produces neurochemical, morphological, and electrophysiological effects reminiscent of those seen in clinical studies of schizophrenia. We will focus on effects of nutritional deficiency that are likely to have implications for schizophrenia. These include disruption of neurotransmitter systems such as dopamine and serotonin and dysgenesis of the hippocampal formation. Preclinical studies show enhanced release and turnover of dopamine and serotonin following prenatal and early postnatal nutritional deficiency. Morphology of the hippocampus, as well as electrophysiology and hippocampally-mediated behaviors are also altered. Although intriguing, these studies have not been conducted with schizophrenia in mind, and thus, outcome measures that may be more specifically related to schizophrenia have not been examined. We propose that further preclinical studies that examine the consequences of prenatal nutritional deficiency, which may lead to altered neuronal migration and other developmental abnormalities, may be useful in understanding the etiology of schizophrenia.

Based on studies of depression and anxiety using animal (rat) models, it is suggested that, contrary to a widely accepted theory, increased activity of locus coeruleus (LC) neurons does not appear to potentiate anxiety; instead, the influence of LC activity may be opposite to this. First, studies are described that indicate that behavioral changes resembling what is seen in human clinical depression occur in rats exposed to highly stressful conditions, and the research is then traced, which links this stress-induced depression to disturbance of normal noradrenergic regulation of LC activity. Second, the potential role of corticotrophin releasing factor (CRF) in stress-induced behavioral depression is explored. CRF infused into the LC did not produce behavioral depression in the swim test but did increase anxiety; by comparison, CRF infused into the parabrachial nucleus lateral to LC increased both depression and anxiety. Finally, to further explore the relationship between LC activity and anxiety, drugs were infused into LC region to attempt to specifically activate or depress firing of LC neurons. In contrast to expectations, infusion to decrease firing of LC cells increased anxious behavior, while infusion to increase firing decreased anxious behavior. Several other studies are discussed that point to a similar conclusion. It is suggested that, at least in rats, the capacity of stress-inducing or aversive stimuli to activate LC neurons does not potentiate anxiety under environmental conditions that elicit this response, but, rather, the increased activity of the LC/dorsal noradrenergic system under such conditions may exert a counterbalancing, antianxiety influence.

The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were “gain control” and “visual integration.” CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development.

Introduction: Schizophrenia patients show decreased ability to identify emotion based upon tone of voice (voice emotion recognition), along with deficits in basic auditory processing. Interrelationship among these measures is poorly understood. Methods: Forty-one patients with schizophrenia/schizoaffective disorder and 41 controls were asked to identify the emotional valence (happy, sad, angry, fear, or neutral) of 38 synthesized frequency-modulated (FM) tones designed to mimic key acoustic features of human vocal expressions. The mean (F0M) and variability (F0SD) of fundamental frequency (pitch) and absence or presence of high frequency energy (HF500) of the tones were independently manipulated to assess contributions on emotion identification. Forty patients and 39 controls also completed tone-matching and voice emotion recognition tasks. Results: Both groups showed a nonrandom response pattern (P < .0001). Stimuli with highest and lowest F0M/F0SD were preferentially identified as happy and sad, respectively. Stimuli with low F0M and midrange F0SD values were identified as angry. Addition of HF500 increased rates of angry and decreased rates of sad identifications. Patients showed less differentiation of response across frequency changes, leading to a highly significant between-group difference in response pattern to maximally identifiable stimuli (d = 1.4). The differential identification pattern for FM tones correlated with deficits in basic tone-matching ability (P = .01), voice emotion recognition (P < .001), and negative symptoms (P < .001). Conclusions: Specific FM tones conveyed reliable emotional percepts in both patients and controls and correlated highly with deficits in ability to recognize information based upon tone of voice, suggesting significant bottom-up contributions to social cognition and negative symptom impairments in schizophrenia.

Context Perceptual closure is the ability to identify objects based on partial information and depends on the function of a distributed network of brain regions that include the dorsal and the ventral visual streams, prefrontal cortex (PFC), and hippocampus. Objective To evaluate network-level interactions during perceptual closure in schizophrenia using parallel event-related potential (ERP), functional magnetic resonance imaging (fMRI), and neuropsychological assessment. Design Case-control study. Setting Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. Patients Twenty-seven patients with schizophrenia or schizoaffective disorder and 23 healthy controls. Intervention Event-related potentials were obtained from 24 patients and 20 healthy volunteers in response to fragmented (closeable) and control-scrambled (noncloseable) line drawings. Functional MRI was performed in 11 patients and 12 controls. Main Outcome Measure Patterns of between-group differences for predefined ERP components and fMRI regions of interest were determined using both analysis of variance and structural equation modeling. Global neuropsychological performance was assessed using standard neuropsychological batteries. Results Patients showed impaired generation of event-related components reflecting early sensory and later closure-related activity. In fMRI, patients showed impaired activation of the dorsal and ventral visual regions, PFC, and hippocampus. Impaired activation of dorsal stream visual regions contributed significantly to impaired PFC activation, which contributed significantly to impaired activation of the hippocampus and ventral visual stream. Impaired ventral stream and hippocampal activation contributed significantly to deficits on neuropsychological measures of perceptual organization. Conclusions Schizophrenia is associated with severe activation deficits across a distributed network of sensory and higher order cognitive regions. Deficit in early visual processing within the dorsal visual stream contributes significantly to impaired frontal activation, which, in turn, leads to dysregulation of the hippocampus and ventral visual stream. Dysfunction within this network underlies deficits in more traditional neurocognitive measures, supporting distributed models of brain dysfunction in schizophrenia.

Background Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia. Methods The study compared performance between patients with schizophrenia ( n = 21) and healthy controls ( n = 20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30° separation. Results For the sound localization task, patients showed reduced accuracy ( p = 0.004) and greater overall response variability ( p = 0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task ( p = 0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task ( p = 0.026), but no significant association was found for the spatial discrimination task. Conclusion Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl's gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning.

Deficits in early visual processing are well documented in schizophrenia, using methods such as contrast sensitivity. Higher, integrative stages of functioning, such as susceptibility to visual illusions, have been evaluated less extensively. For example, patients show increased susceptibility to (ie, are more easily affected by) the Muller-Lyer illusion but decreased susceptibility (ie, are less easily affected by) to stereopsis based upon binocular disparity. The basis for pattern of illusion response and interaction between sensory and integrative stages of processing, however, is unclear. We tested a group of 38 patients and 28 control subjects in contrast sensitivity, the Muller-Lyer and Poggendorff illusions, as well as a subgroup in stereopsis and the Ponzo illusion, Sander parallelogram, and Hermann grid illusions. We predicted that patients would be more susceptible to tests that become more apparent with increased contrast (Muller-Lyer illusion), less susceptible to tests that become less apparent with increased contrast (stereopsis, Ponzo illusion, Hermann grid), and equally susceptible to contrast-insensitive tests (Poggendorff illusion). Additionally, the Hermann grid was tested at varying levels of contrast. Patients demonstrated significant deficits in contrast sensitivity, especially to brief, low spatial frequency stimuli, and the predicted differential response to the tested illusions. Additionally, poor performance on stereopsis and the Hermann grid significantly correlated with decreased contrast sensitivity (all P's

Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed.

The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were gain control and visual integration. CNTRICS received 5 task nominations for gain control and three task nominations for visual integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group for perception believed that 2 of the tasks (prepulse inhibition of startle and mismatch negativity) were already mature and in the process of being incorporated into multisite clinical trials. However, the breakout group recommended that steady-state visual-evoked potentials be combined with contrast sensitivity to magnocellular vs parvocellular biased stimuli and that this combined task and the contrast-contrast effect task be recommended for translation for use in clinical trial contexts in schizophrenia research. For visual integration, the breakout group recommended the Contour Integration and Coherent Motion tasks for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to evaluate and recommend tasks for further development.