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Neurophysiological, Oculomotor, and Computational Modeling of Impaired Reading Ability in Schizophrenia
Dias, Elisa C; Sheridan, Heather; Martínez, AntÃgona; Sehatpour, Pejman; Silipo, Gail; Rohrig, Stephanie; Hochman, Ayelet; Butler, Pamela D; Hoptman, Matthew J; Revheim, Nadine; Javitt, Daniel C
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.
PMCID:7825085
PMID: 32851415
ISSN: 1745-1701
CID: 4798342
Comparison of Scalp ERP to Faces in Macaques and Humans
Orczyk, John; Schroeder, Charles E; Abeles, Ilana Y; Gomez-Ramirez, Manuel; Butler, Pamela D; Kajikawa, Yoshinao
Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.
PMCID:8101630
PMID: 33967709
ISSN: 1662-5137
CID: 4867082
Optical coherence tomography of the retina in schizophrenia: Inter-device agreement and relations with perceptual function
Miller, Margaret; Zemon, Vance; Nolan-Kenney, Rachel; Balcer, Laura J; Goff, Donald C; Worthington, Michelle; Hasanaj, Lisena; Butler, Pamela D
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.
PMID: 31937481
ISSN: 1573-2509
CID: 4264382
Grant Report on Social Reward Learning in Schizophrenia â€
Butler, Pamela D; Hoptman, Matthew J; Smith, David V; Ermel, Julia A; Calderone, Daniel J; Lee, Sang Han; Barch, Deanna M
We report on the ongoing R21 project "Social Reward Learning in Schizophrenia". Impairments in social cognition are a hallmark of schizophrenia. However, little work has been done on social reward learning deficits in schizophrenia. The overall goal of the project is to assess social reward learning in schizophrenia. A probabilistic reward learning (PRL) task is being used in the MRI scanner to evaluate reward learning to negative and positive social feedback. Monetary reward learning is used as a comparison to assess specificity. Behavioral outcomes and brain areas, included those involved in reward, are assessed in patients with schizophrenia or schizoaffective disorder and controls. It is also critical to determine whether decreased expected value (EV) of social stimuli and/or reward prediction error (RPE) learning underlie social reward learning deficits to inform potential treatment pathways. Our central hypothesis is that the pattern of social learning deficits is an extension of a more general reward learning impairment in schizophrenia and that social reward learning deficits critically contribute to deficits in social motivation and pleasure. We hypothesize that people with schizophrenia will show impaired behavioral social reward learning compared to controls, as well as decreased ventromedial prefrontal cortex (vmPFC) EV signaling at time of choice and decreased striatal RPE signaling at time of outcome, with potentially greater impairment to positive than negative feedback. The grant is in its second year. It is hoped that this innovative approach may lead to novel and more targeted treatment approaches for social cognitive impairments, using cognitive remediation and/or brain stimulation.
PMCID:7089616
PMID: 32206729
ISSN: 2398-385x
CID: 4357732
A Vision for Psychosis Research: Commentary on "New Insights into Schizophrenia: a Look at the Eye and Related Structures"
Malaspina, Dolores; Butler, Pamela D
PMID: 32303032
ISSN: 0353-5053
CID: 4383942
The P1 Visual-Evoked Potential, Red Light, and Transdiagnostic Psychiatric Symptoms
Bedwell, Jeffrey S; Spencer, Christopher C; Chan, Chi C; Butler, Pamela D; Sehatpour, Pejman; Schmidt, Joseph
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.
PMCID:5882500
PMID: 29510142
ISSN: 1872-6240
CID: 2975162
Associations Between Contrast Processes and Resting-State Functional Connectivity in Patients With Schizophrenia and Healthy Controls [Meeting Abstract]
Herrera, Shaynna; Butler, Pamela D.; Zemon, Vance; Javitt, Daniel C.; Hoptman, Matthew J.
ISI:000433001900534
ISSN: 0006-3223
CID: 3140392
Visual perceptual remediation for individuals with schizophrenia: Rationale, method, and three case studies
Butler, Pamela D; Thompson, Judy L; Seitz, Aaron R; Deveau, Jenni; Silverstein, Steven M
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
PMCID:5322250
PMID: 27547852
ISSN: 1559-3126
CID: 2525082
What can the study of first impressions tell us about attitudinal ambivalence and paranoia in schizophrenia?
Tremeau, Fabien; Antonius, Daniel; Todorov, Alexander; Rebani, Yasmina; Ferrari, Kelsey; Lee, Sang Han; Calderone, Daniel; Nolan, Karen A; Butler, Pamela; Malaspina, Dolores; Javitt, Daniel C
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'.
PMID: 27086216
ISSN: 1872-7123
CID: 2079282
Implicit emotion perception in schizophrenia
Tremeau, Fabien; Antonius, Daniel; Todorov, Alexander; Rebani, Yasmina; Ferrari, Kelsey; Lee, Sang Han; Calderone, Daniel; Nolan, Karen A; Butler, Pamela; Malaspina, Dolores; Javitt, Daniel C
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.
PMID: 26473695
ISSN: 1879-1379
CID: 1803782