Contrast sensitivity deficits in schizophrenia: A psychophysical investigation.

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

Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine.

Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task. In a second cohort (n = 21 schizophrenia/schizoaffective patients, n = 13 healthy controls), event-related potential and event-related time-frequency measures of auditory dysfunction were assessed during administration of the NMDAR agonist d-serine. Mismatch negativity was used as a functional read-out of auditory-level function. Clinical trials registration numbers were NCT01474395/NCT02156908 Schizophrenia/schizoaffective patients showed significantly reduced auditory plasticity versus healthy controls (P = 0.001) that correlated with measures of cognitive, occupational and social dysfunction. In event-related potential/time-frequency analyses, patients showed highly significant reductions in sensory N1 that reflected underlying impairments in θ responses (P < 0.001), along with reduced θ and ß-power modulation during retention and motor-preparation intervals. Repeated administration of d-serine led to intercorrelated improvements in (i) auditory plasticity (P < 0.001); (ii) θ-frequency response (P < 0.05); and (iii) mismatch negativity generation to trained versus untrained tones (P = 0.02). Schizophrenia/schizoaffective patients show highly significant deficits in auditory plasticity that contribute to cognitive, occupational and social dysfunction. d-serine studies suggest first that NMDAR dysfunction may contribute to underlying cortical plasticity deficits and, second, that repeated NMDAR agonist administration may enhance cortical plasticity in schizophrenia.

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

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

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

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

Spirituality, schizophrenia, and state hospitals: program description and characteristics of self-selected attendees of a spirituality therapeutic group.

Spiritual matters can be an important part in the recovery process of patients with schizophrenia. A spirituality-based therapeutic group was developed for patients hospitalized on a research specialty unit jointly operated by a state hospital and a research institute. This report offers a description of this program and examines potential associations between spirituality and coping in patients with schizophrenia who either attended or did not attend the inpatient spirituality group. We compared group attendees (n = 20) with non-attendees (n = 20) cross-sectionally, using measures of spirituality, self-efficacy (i.e. the confidence in one's ability), quality of life, and hopefulness, and religious/personal demographic profiles. For the total sample, spirituality status was significantly correlated with self-efficacy for both social functioning and negative symptoms. Significant differences were found between group attendees and non-attendees for spirituality status, but not for self-efficacy or quality of life. For group attendees, spirituality status was significantly correlated with self-efficacy for positive symptoms, negative symptoms and social functioning. Group attendees were significantly more hopeful than non-attendees and hopefulness was significantly associated with degree of spirituality status. These findings lend support for offering spirituality groups and positive coping during recovery from psychiatric disabilities.

It's all in the cards: effect of stimulus manipulation on Wisconsin Card Sorting Test performance in schizophrenia.

Patients with schizophrenia can be taught the Wisconsin Card Sorting Test (WCST) sorting rules based upon expanded feedback. However, few task manipulations have been reported that differentially improve patient performance without altering the nature of feedback provided. The present study tests the hypothesis that deficits in WCST performance in schizophrenia reflect, in part, impaired ability to manipulate abstract stimulus features, rather than impaired ability to utilize feedback. We developed a modified stimulus set - the Rockland Face Sorting Test (RFST) - in which abstract shapes were replaced with faces, which we hypothesized would be more tractable to sorting by patients. Task rules and feedback remained unchanged. Relative RFST and WCST performance was examined in 19 patients as well as 15 normative controls. A comparison group of 15 patients received only repeated WCST administrations. Patients performed significantly better on the RFST vs. the WCST in categories completed, total correct responses and conceptual level responses, whereas no improvement was seen in either the normative or repeated WCST comparison groups. Furthermore, progressive improvement was seen following repeated RFST administration. These findings demonstrate that stimulus characteristics, as well as executive deficits, contribute to impaired WCST performance in schizophrenia.

Spirituality matters: creating a time and place for hope.

Individuals with serious psychiatric disabilities may become demoralized or hopeless consequent to longstanding disability and stigma. Potential antidotes are social support from the religious community and use of personal spiritual resources as coping mechanisms. The "Spirituality Matters Group" offers comfort and hope through structured and innovative exercises focusing on spiritual beliefs and coping. Activities facilitate verbal expression and appropriate social interaction, and build a sense of community. Activities and themes from selected group sessions are discussed within a recovery-oriented "emotion-focused coping" framework.

Reading impairment and visual processing deficits in schizophrenia.

Individuals with schizophrenia show magnocellular visual pathway abnormalities similar to those described in dyslexia, predicting that reading disturbance should be a common concomitant of schizophrenia. To date, however, reading deficits have not been well established, and, in fact, reading is often thought to be normal in schizophrenia based upon results of tests such as the WRAT, which evaluate single word reading. This study evaluated "real world" reading ability in schizophrenia, relative to functioning of the magnocellular visual pathway. Standardized psychoeducational reading tests and contrast sensitivity measures were administered to 19 patients and 10 controls. Analyses of between group differences were further refined by classification of participants into reading vs. non-reading impaired groups using a priori and derived theoretical models. Patients with schizophrenia, as a group, showed highly significant impairments in reading (p<0.04-p<0.001), with particular deficits on tests of rate, comprehension and phonological awareness. Between 21% and 63% of patients met criteria for dyslexia depending upon diagnostic model vs. 0-20% of the controls. The degree of deficit correlated significantly with independent measures of magnocellular dysfunction. Reading impairment in schizophrenia reaches the level of dyslexia and is associated with compromised magnocellular processing as hypothesized. Findings related to symptoms, functioning and recommendations for reading ability assessment are discussed.

Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia.

Functional outcome for individuals with schizophrenia has been associated with cognitive impairment. Deficits in attention, memory, speed of information processing and problem-solving skills affect independent functioning, vocational performance, and interpersonal functioning. This study investigated the relationship between neurocognitive functioning, clinical symptoms and daily problem-solving skills in seriously and persistently ill persons. Thirty-eight inpatients and outpatients were administered a neurocognitive battery for attention, working memory, processing speed, perceptual organization, and executive functioning; and semi-structured clinical interviews using the BPRS and SANS. Estimates of daily problem-solving skills were obtained using the relevant factor subscale from the Independent Living Scales (ILS-PB). Daily problem-solving skills were significantly correlated with negative symptoms, processing speed, verbal memory, and working memory scores. A regression model using an enter method suggests that working memory and negative symptoms are significant predictors of daily problem-solving skills and account for 73.2% of the variance. Further analyses demonstrate that daily problem-solving skills and negative symptoms were significantly different for inpatients and outpatients and significantly correlated with community status. The findings suggest the ILS-PB has utility as a proxy measure for assessing real-world functioning in schizophrenia.

Early-stage visual processing and cortical amplification deficits in schizophrenia.

BACKGROUND: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an inpatient state psychiatric hospital and outpatient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. RESULTS: Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P = .001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P = .002), which was in turn related to deficits in complex visual processing (P< or =.04). Both evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures significantly predicted community functioning. CONCLUSIONS: These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.

Group treatment approaches to address cognitive deficits.

Psychiatric rehabilitation services are primarily delivered using group modalities. Recent evidence points to the deleterious effects of poor cognitive functioning on group involvement, skill development and functional outcomes. This paper reviews the impact of individual cognitive deficits on group functioning, discusses the rationale for using a cognitive framework for group development, and presents multiple examples of group programming with compensatory and remediation techniques to improve group functioning. Examples include modifying groups to address cognitive limitations, as well as developing groups targeting specific cognitive functions. The groups described are suitable for persons with serious and persistent mental illness across hospital and community treatment settings.

Sensory contributions to impaired prosodic processing in schizophrenia.

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.

Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia.

OBJECTIVE: Patients with schizophrenia demonstrate significant impairments of early visual processing, potentially implicating dysfunction of the magnocellular visual pathway. The present study evaluates transient visual evoked potential (tVEP) responses to stimuli biased toward the magnocellular (M) or parvocellular (P) systems in patients with schizophrenia vs. normal volunteers first to evaluate relative contributions of M and P systems to specific tVEP components in schizophrenia and, second, to evaluate integrity of early M and P processing in schizophrenia. METHODS: Seventy-four patients with schizophrenia and schizoaffective disorder were compared with 59 control subjects using separate stimuli to assess the tVEP response to M, P and mixed M/P conditions. Stimuli were biased toward M vs. P processing by manipulation of chromatic and achromatic contrast. C1, P1, N1 and P2 components were compared between patients and controls. All subjects showed 20/32 vision or better. RESULTS: Waveforms were obtained to low contrast (M), chromatic contrast (P) and high contrast (mixed M/P) stimuli in both patients and controls. C1 was present to P and mixed M/P stimuli. Patients showed a significant reduction in amplitude and an increase in latency of the C1 component. P1 was elicited primarily by M and mixed M/P stimuli, whereas N1 was elicited primarily by P and mixed M/P stimuli. Patients showed reductions in both P1 and N1 amplitudes across conditions. However, only reductions in P1 amplitude survived covariation for between group differences in visual acuity. Further, P1 amplitude reductions in the M condition correlated with a proxy measure of global outcome. CONCLUSIONS: M- and P-selective stimuli elicit differential components of the tVEP. Patients with schizophrenia show significant reductions in response even to simple visual stimuli. Deficits, particularly within the M system, may correlate significantly with global outcome and level of community functioning. SIGNIFICANCE: Whereas deficits in high-order cognitive processing have been extensively documented in schizophrenia, integrity of early-stage sensory processing has been studied to a lesser degree. The present findings suggest that deficits in early-stage visual processing are significantly related to overall clinical outcome in schizophrenia. Further, between-group differences in visual acuity may influence VEP results, even for subjects with 'normal' vision (20/32 or better).

Verbal memory, problem-solving skills and community status in schizophrenia.

Neuropsychological deficits have been associated with poor community functioning in individuals with schizophrenia. Previous research suggests that verbal memory capacity is related to functional capacity. The purpose of this study was to investigate the relationship between verbal memory, problem-solving skills and community functioning, as measured by treatment status (inpatient vs. outpatient) in people with schizophrenia spectrum disorders. Evaluations were done on 162 individuals with schizophrenia or schizoaffective disorder, seen in inpatient (n=87) and outpatient settings (n=75). Verbal memory was assessed using narrative recall and list recall measures. Problem-solving skills for independent living were assessed using a social reasoning measure and a daily problem-solving skills measure. Better verbal memory performance was associated with better problem solving for independent living. However, inpatient vs. outpatient status was best determined by problem-solving skills for independent living rather than verbal memory performance. The results reveal the importance of daily problem-solving skills for community status in schizophrenia. Although verbal memory performance is associated with problem-solving skills for independent living, predictive probability of community status does not improve when memory performance is taken into account.

Remediation of problem-solving skills in schizophrenia: evidence of a persistent effect.

Neuropsychological deficits in problem solving are commonly found in patients with schizophrenia. We have previously presented the results of a study examining the feasibility of utilizing problem-solving teaching techniques developed within educational psychology, for remediating the problem-solving deficits of inpatients with schizophrenia spectrum disorders. These techniques emphasize the importance of intrinsic motivation on therapeutic outcome and promote this through contextualization, personalization and control of learning activities. We present here the results of the follow-up assessment, which found that the gains made by the problem-solving group persisted for 4 weeks after cessation of problem-solving remediation ended. These results provide more evidence of the therapeutic benefit of problem-solving training techniques that promote intrinsic motivation and generic problem-solving strategies.

The impact of cognitive remediation on psychiatric symptoms of schizophrenia.

OBJECTIVE: The relationship between psychopathology and cognitive functioning in schizophrenia is of interest, both for an understanding of the nature of the disease, and for comprehensive treatment planning. The aim of this study was to investigate how psychiatric symptoms affect, and are affected by, cognitive remediation. METHOD: Fifty-four psychiatric inpatients received either cognitive remediation exercises (remediation group) or no cognitive intervention (control group). The subjects' scores on tests of cognition and on the Positive and Negative Symptoms Scale (PANSS) were measured before, after the 10 session treatment, and again 4 weeks post treatment. RESULTS: Only the remediation group showed significant and persistent improvement on all three PANSS Subscales as well as on the Positive Symptoms and Depression Factors. There were no significant between-group differences on any PANSS pre/posttreatment change scores. Baseline measures of psychopathology did not correlate meaningfully with amount of change made on cognitive measures after rehabilitation. CONCLUSIONS: A brief 10-session course of cognitive remediation is sufficient to benefit cognition and has some positive effects on psychopathology as measured by the PANSS, but does not add significantly to the effects of standard psychiatric treatment on psychopathology. Furthermore, psychiatric symptom profile is not predictive of the degree to which cognitive symptoms respond to cognitive remediation. The differential impact of cognitive remediation on cognition and psychopathology may imply that psychopathology and cognitive functioning follow fairly independent treatment courses.

The independent living scales as a measure of functional outcome for schizophrenia.

The Independent Living Scales (ILS) measures cognitive skills required for independent living and is intended to provide guidelines for appropriate supervision requirements for persons in residential placement. To assess the validity of the ILS among persons with schizophrenia, the instrument was administered to 162 individuals with schizophrenia who were living in three gradations of care: maximum supervision, moderate supervision, and minimal supervision. Scores on the ILS differed significantly across the three levels of care, whereas scores on the Global Assessment of Functioning (GAF) that were provided by clinicians discriminated only two levels of care. The ILS can be used among patients with schizophrenia to measure cognition as it affects functional outcome.

Reading deficits in schizophrenia and individuals at high clinical risk: relationship to sensory function, course of illness, and psychosocial outcome.

OBJECTIVE: 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. METHOD: 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. RESULTS: Schizophrenia patients displayed reading deficits that were far more severe (effect size >2.0) 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. CONCLUSIONS: 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.

Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia.

In healthy humans, passage reading depends upon a critical organizing role played by the magnocellular/dorsal visual pathway. In a recent study, we found a significant correlation between orthographic reading deficits in schizophrenia and deficits in contrast sensitivity to low spatial frequency stimuli, suggesting an underlying magnocellular processing abnormality. The interrelationship between magnocellular dysfunction and passage reading impairments in schizophrenia was investigated in 21 patients with schizophrenia and 17 healthy control volunteers using behavioral and functional MRI (fMRI) based measures. fMRI activation patterns during passage- and single-word reading were evaluated in relation to cortical areas with differential sensitivity to low versus high spatial frequency cortical regions indentified using a phase-encoded fMRI paradigm. On average, patients with schizophrenia read at the 6th grade level, despite completion of more than 12 years of education and estimated normal pre-morbid IQ. Schizophrenia patients also showed significantly impaired contrast sensitivity to low spatial frequencies and abnormal neural activity in response to stimulation with low spatial frequencies, consistent with dysfunction of magnocellular processing. Further, these magnocellular deficits were predictive of poor performance on a standardized psychoeducational test of passage reading. These findings suggest that reading is an important index of cognitive dysfunction in schizophrenia and highlight the contribution of magnocellular dysfunction to overall cognitive impairments in schizophrenia.