Ensemble Statistics Can Be Available before Individual Item Properties: Electroencephalography Evidence Using the Oddball Paradigm.

Behavioral studies have shown that statistical properties of object groups are perceived accurately with brief exposure durations. This finding motivated the hypothesis that ensemble perception occurs rapidly in vision. However, the precise timing of ensemble perception remains unclear. Here, we used the superior temporal resolution of electroencephalography to directly compare the timing of ensemble processing to that of individual object processing. The P3b was chosen as a particular component of interest, as it is thought to measure the latency of stimulus evaluation. Participants performed a simple "oddball" task in which sets of 51 lines with varied orientations sequentially flashed briefly on the display. In these sequences, there was a 20% chance of an individual oddball, wherein one marked object tilted clockwise, and a 20% chance of an ensemble oddball, wherein the average orientation of the set tilted clockwise. In counterbalanced blocks, participants were instructed to respond to either individual or ensemble oddballs. ERP analysis was performed to test the timing of this processing. At parietal electrodes, P3b components were found for both individual and ensemble oddballs. Ensemble P3b components were found to occur significantly earlier than individual P3b components, as measured with both 50% area latency and 50% onset latency. Using multivariate pattern analysis, ensemble oddball trials were classifiable from standard trials significantly earlier in their timecourse than individual oddball trials. Altogether, these results provide compelling evidence that ensemble perception occurs rapidly and that ensemble properties can be available earlier than individual object properties.

The outlier paradox: The role of iterative ensemble coding in discounting outliers.

Ensemble perception-the encoding of objects by their group properties-is known to be resistant to outlier noise. However, this resistance is somewhat paradoxical: how can the visual system determine which stimuli are outliers without already having derived statistical properties of the ensemble? A simple solution would be that ensemble perception is not a simple, one-step process; instead, outliers are detected through iterative computations that identify items with high deviance from the mean and reduce their weight in the representation over time. Here we tested this hypothesis. In Experiment 1, we found evidence that outliers are discounted from mean orientation judgments, extending previous results from ensemble face perception. In Experiment 2, we tested the timing of outlier rejection by having participants perform speeded judgments of sets with or without outliers. We observed significant increases in reaction time (RT) when outliers were present, but a decrease compared to no-outlier sets of matched range suggesting that range alone did not drive RTs. In Experiment 3 we tested the timing by which outlier noise reduces over time. We presented sets for variable exposure durations and found that noise decreases linearly over time. Altogether these results suggest that ensemble representations are optimized through iterative computations aimed at reducing noise. The finding that ensemble perception is an iterative process provides a useful framework for understanding contextual effects on ensemble perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms.

BACKGROUND: Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist. This study investigates effects of continuous (daily) NMDAR agonists in schizophrenia/schizoaffective disorder. METHODS: Primary analysis was on MMN after double-blind crossover (60mg/kg/d, n=16, 6weeks) treatment with d-serine/placebo. Secondary measures included clinical symptoms, neurocognition, and the effects of open-label (30-120mg/kg/d, n=21) d-serine and bitopertin/placebo (10mg, n=29), a glycine transport inhibitor. RESULTS: Double-blind d-serine treatment led to significant improvement in MMN frequency (p=0.001, d=2.3) generation and clinical symptoms (p=0.023, d=0.80). MMN frequency correlated significantly with change in symptoms (r=-0.63, p=0.002) following co-variation for treatment type. d-Serine treatment led to a significant, large effect size increase vs. placebo in evoked α-power in response to standards (p=0.036, d=0.81), appearing to normalize evoked α power relative to previous findings with controls. While similar results were seen with open-label d-serine, no significant effects of bitopertin were observed for symptoms or MMN. CONCLUSIONS: These findings represent the first randomized double-blind placebo-controlled study with 60mg/kg d-serine in schizophrenia, and are consistent with meta-analyses showing significant effects of d-serine in schizophrenia. Results overall support suggest that MMN may have negative, as well as positive, predictive value in predicting efficacy of novel compounds. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov: NCT00322023/NCT00817336 (d-serine); NCT01116830 (bitopertin).

Neurophysiological Effects of Bitopertin in Schizophrenia.

PURPOSE/BACKGROUND: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist D-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia. METHODS/PROCEDURES: Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance. FINDINGS/RESULTS: No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments. IMPLICATIONS/CONCLUSIONS: These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.

Ensemble coding remains accurate under object and spatial visual working memory load.

A number of studies have provided evidence that the visual system statistically summarizes large amounts of information that would exceed the limitations of attention and working memory (ensemble coding). However the necessity of working memory resources for ensemble coding has not yet been tested directly. In the current study, we used a dual task design to test the effect of object and spatial visual working memory load on size averaging accuracy. In Experiment 1, we tested participants' accuracy in comparing the mean size of two sets under various levels of object visual working memory load. Although the accuracy of average size judgments depended on the difference in mean size between the two sets, we found no effect of working memory load. In Experiment 2, we tested the same average size judgment while participants were under spatial visual working memory load, again finding no effect of load on averaging accuracy. Overall our results reveal that ensemble coding can proceed unimpeded and highly accurately under both object and spatial visual working memory load, providing further evidence that ensemble coding reflects a basic perceptual process distinct from that of individual object processing.

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.

Abnormal task modulation of oscillatory neural activity in schizophrenia.

Schizophrenia patients have deficits in cognitive function that are a core feature of the disorder. AX-CPT is commonly used to study cognition in schizophrenia, and patients have characteristic pattern of behavioral and ERP response. In AX-CPT subjects respond when a flashed cue "A" is followed by a target "X," ignoring other letter combinations. Patients show reduced hit rate to "go" trials, and increased false alarms to sequences that require inhibition of a prepotent response. EEG recordings show reduced sensory (P1/N1), as well as later cognitive components (N2, P3, CNV). Behavioral deficits correlate most strongly with sensory dysfunction. Oscillatory analyses provide critical information regarding sensory/cognitive processing over and above standard ERP analyses. Recent analyses of induced oscillatory activity in single trials during AX-CPT in healthy volunteers showed characteristic response patterns in theta, alpha, and beta frequencies tied to specific sensory and cognitive processes. Alpha and beta modulated during the trials and beta modulation over the frontal cortex correlated with reaction time. In this study, EEG data was obtained from 18 schizophrenia patients and 13 controls during AX-CPT performance, and single trial decomposition of the signal yielded power in the target wavelengths. Significant task-related event-related desynchronization (ERD) was observed in both alpha and beta frequency bands over parieto-occipital cortex related to sensory encoding of the cue. This modulation was reduced in patients for beta, but not for alpha. In addition, significant beta ERD was observed over motor cortex, related to motor preparation for the response, and was also reduced in patients. These findings demonstrate impaired dynamic modulation of beta frequency rhythms in schizophrenia, and suggest that failures of oscillatory activity may underlie impaired sensory information processing in schizophrenia that in turn contributes to cognitive deficits.

A high school-based voluntary cardiovascular risk screening program: issues of feasibility and correlates of electrocardiographic outcomes.

Risk factors for adult cardiovascular events can be identified from the prenatal period through childhood. We performed a cardiovascular risk-screening program in students from grades 9-12 in 7 high schools in Hillsborough County, FL. We obtained blood pressure (BP) measurements and calculated body mass index (BMI) as risk factors for future cardiovascular events as well as obtained an electrocardiogram (ECG) for the purposes of detecting possible life-threatening arrhythmias. Of ~14,000 students contacted, 600 (4 %) participated in the screening. Of these, 517 (86 %) were diagnosed with normal, 71 (12 %) with borderline, and 12 (1 %) with abnormal ECGs. Although no participant had any cardiac history, two of the abnormal ECGs indicated a cardiac diagnosis associated with the potential for sudden cardiac death. Both systolic and diastolic BP increased as the ECG diagnosis moved from normal (115.6/73.8) through borderline (121.0/75.9) to an abnormal (125.0/80.7) diagnosis (all P ≤ .0016). An increase in BMI was only observed when an ECG diagnosis was abnormal (P = .0180). Boys had a greater prevalence (18.97 %) of borderline or abnormal ECGs compared with girls (6.75 %), whereas no discernible differences were seen in ECG diagnosis between white and nonwhite individuals (15.09 and 12.26 %, respectively). Although participation rates were low, a high school-based cardiovascular risk-screening program including ECG is feasible. Although ECG diagnosis tended to be related to other known cardiovascular risk factors (BP, BMI), the utility of an abnormal ECG in adolescence as a predictor of future cardiovascular risk will require further evaluation in more controlled settings.

Longitudinal changes in heart rate-corrected measures of exercise performance in children.

Interpretation of change in exercise performance over time in children with repaired congenital heart disease is often hampered by poor effort that limits the maximum heart rate; this is often difficult to distinguish from chronotropic impairment, a common finding in these children. In an attempt to address this limitation, we sought to examine measures of exercise performance that are corrected for heart rate in healthy children and to determine if these change with somatic growth. We studied two serial graded exercise tests in 24 healthy children at an interval of >3 years. Paired comparisons revealed that maximum oxygen pulse (O(2) pulse), O(2) pulse at ventilatory anaerobic threshold, O(2) pulse at a heart rate of 140 beats per minute, and slope of the VO(2)-heart rate relationship all increased with age. However, when indexed to somatic growth, there was no change in the mean values of these parameters over time. We conclude that O(2 )pulse and slope of the VO(2)-heart rate relationship during exercise increase in proportion to somatic growth in children so that optimal oxygen delivery to the exercising muscles is ensured. This study provides the "normative" response of exercise parameters to growth, against which responses of children with repaired congenital heart disease may be compared.

Is it safe to perform cardiac catheterizations on adults with congenital heart disease in a pediatric catheterization laboratory?

OBJECTIVE: To determine the complication rate during the catheterization in adults with congenital heart disease (CHD) in a pediatric catheterization laboratory (PCL). BACKGROUND: An increasing number of patients with CHD are surviving into adulthood, with diagnostic and interventional cardiac catheterization being essential for the management of their disease. The complication rate during the catheterization of adults with CHD has not been reported. METHODS: A retrospective chart review was performed on all adult patients (>18 years) with CHD who underwent diagnostic or interventional catheterization in our PCL within the past 8.5 years. RESULTS: A total of 576 procedures were performed on 436 adult patients (median age 26 years). Complex heart disease was present in 387/576 (67%) procedures. An isolated atrial septal defect or patent foramen ovale was present in 115/576 (20%) procedures, and 51/576 (9%) procedures were performed on patients with structurally normal hearts with arrhythmias. Interventional catheterization was performed in 378/576 (66%) procedures. There were complications during 61/576 (10.6%) procedures; 19 were considered major and 42 minor. Major complications were death (1), ventricular fibrillation (1), hypotension requiring inotropes (7), atrial flutter (3), retroperitoneal hematoma, pneumothorax, hemothorax, aortic dissection, renal failure, myocardial ischemia and stent malposition (1 each). The most common minor complications were vascular entry site hematomas and hypotension not requiring inotropes. Procedures performed on patients > or = 45 years of age had a 19% occurrence of complications overall compared with 9% occurrence rate in patients of age < 45 years (P < 0.01). CONCLUSIONS: The complication rate during the catheterization of adults with CHD in a PCL is similar to the complication rate of children with CHD undergoing cardiac catheterization. The older subset of patients are more likely to encounter complications overall. The encountered complications could be handled effectively in the PCL. With screening in place, it is safe to perform cardiac catheterization on most adults with CHD in a PCL.

Transthoracic echocardiography for precardioversion screening during atrial flutter/fibrillation in young patients.

BACKGROUND: Transthoracic echocardiography (TTE) is reliable for detection of thrombi in the left ventricle and right atrium, but not in the left atrial appendage. Therefore, transesophageal echocardiography (TEE) is routinely performed in adults prior to electric cardioversion for atrial flutter/fibrillation (AFF). Whether young survivors of congenital heart disease repair with AFF need routine TEE prior to electric cardioversion is unknown. HYPOTHESIS: Electric cardioversion for AFF is safe in survivors of congenital heart disease repair/palliation if an intracardiac thrombus is not suspected on TTE imaging. METHODS: This study reports the outcome of patients in a pediatric tertiary care cardiac unit where electric cardioversion was performed if no intracardiac thrombus was suspected on TTE. We performed a retrospective chart review of all patients treated with electric cardioversion for AFF at Children's Hospital of Michigan during 1997-2002. RESULTS: Of 35 patients who presented with 110 episodes of AFF requiring electric cardioversion during the study duration, 32 (age 3 months-49 years, median age 20.5 years, 104 AFF episodes) had previously undergone palliative surgery or repair of their congenital heart disease. Of these 32 patients, 18 were survivors of a Fontan palliation (for a single-ventricle variant) and the remaining 14 were survivors of other defects and repairs (septal defects, valve replacements, and tetralogy of Fallot). During 81% of the episodes, patients were receiving aspirin, warfarin, or heparin for anticoagulation at presentation. Transthoracic echocardiography was performed in 74 AFF episodes; of these, 10 TTE studies were suspicious for atrial thrombi. Transesophageal echocardiography confirmed the presence of a thrombus in 3 of these 10 patients. These patients received warfarin for 2 weeks and then underwent electric cardioversion. No thromboembolic events occurred immediately after or on follow-up in any patient. CONCLUSIONS: These findings suggest that TTE may be an effective imaging tool for precardioversion screening in young patients with AFF.

Abrupt aortic root dilation after the Ross procedure--is this a progressive phenomenon?

This study provides evidence of aortic root dilation in children, adolescents, and young adults who have undergone the Ross procedure. Several mechanisms are described.

Loffler's endocarditis presenting in 2 children as fever with eosinophilia.

Hypereosinophilic syndromes are defined by the presence of peripheral and bone marrow eosinophilia and by the infiltration of multiple organs by mature eosinophilic cells. Loffler's endocarditis is a condition in which mature eosinophils infiltrate and damage the endocardium and myocardium. Male adults who live in the tropics are the population predominantly affected by this condition. Typical clinical features include weight loss, fever, cough, rash, and congestive heart failure. In this article, we report the typical presentation of an unusual illness that occurred in 2 pediatric patients in different geographic locations. In addition, we believe that these are the youngest patients with Loffler's endocarditis reported.

Students prefer the immediate feedback assessment technique.

Students responded to a questionnaire after completing classroom examinations using either Scantron forms or the Immediate Feedback Assessment Technique. Factor analysis of students' responses yielded six scales unrelated to students' grades and not differing by sex, course, or instructor. Students evaluated on the latter technique scored significantly higher on scales measuring ease of understanding and ease of completing response requirements, perceived fairness of and preference for an answer-until-correct procedure, and enhanced involvement in the test-taking process.

Early reopening and recanalization after successful coil occlusion of the patent ductus arteriosus.

BACKGROUND: Controversy exists regarding early reopening and recanalization after successful (complete) coil occlusion of the patent ductus arteriosus (PDA). METHODS: Patients with successful PDA coil occlusion were reviewed with regard to PDA size and type, coil size, number of coils, and delivery technique. Follow-up echocardiograms at <24 hours, 6 months, and >12 months were reviewed for residual PDA shunt, left pulmonary artery (LPA) stenosis, and aortic obstruction. RESULTS: Successful coil occlusion was achieved in 94 patients. On the initial (<24 hours) echocardiogram, 76 of 92 (83%) had complete PDA occlusion, 5 of 92 (5%) had mild LPA stenosis, and no patient had aortic obstruction. Follow-up at 6 months was available in 70 patients, 57 with complete occlusion on the initial echocardiogram. PDA reopening was found in 3 of 57 patients (5%). Larger PDA diameter was associated with residual shunt (2.40 +/- 0.40 mm versus 1.87 +/- 0.53 mm; P <.01). Disagreement between the initial and 6-month echocardiogram was found in 11 of 70 patients (16%). Intermediate follow-up (median, 30 months; range, 12 months to 5.3 years) was available in 46 patients, 38 with complete occlusion on the 6-month echocardiogram. No patient (0 of 38) with a normal echocardiogram at 6 months developed recanalization, LPA stenosis, or aortic obstruction. CONCLUSION: These data suggest that: (1) routine echocardiography immediately after PDA coil occlusion is unnecessary; (2) early PDA reopening is uncommon; and (3) PDA recanalization does not occur if complete echocardiographic closure is documented 6 months after coil occlusion. Additional follow-up examination in these patients may not be necessary.

Immediate Feedback Assessment Technique: multiple-choice test that "behaves" like an essay examination.

A multiple-choice testing system that provides immediate affirming or corrective feedback and permits allocation of partial credit for proximate knowledge is suggested as an alternative to essay examinations.