Intrauterine devices in the management of postpartum hemorrhage.

Obstetrical hemorrhage is a relatively frequent obstetrical complication and a common cause of maternal morbidity and mortality worldwide. The majority of maternal deaths attributable to hemorrhage are preventable, thus, developing rapid and effective means of treating postpartum hemorrhage is of critical public health importance. Intrauterine devices are one option for managing refractory hemorrhage, with rapid expansion of available devices in recent years. Intrauterine packing was historically used for this purpose, with historical cohorts documenting high rates of success. Modern packing materials, including chitosan-covered gauze, have recently been explored with success rates comparable to uterine balloon tamponade in small trials. There are a variety of balloon tamponade devices, both commercial and improvised, available for use. Efficacy of 85.9% was cited in a recent meta-analysis in resolution of hemorrhage with the use of uterine balloon devices, with greatest success in the setting of atony. However, recent randomized trials have demonstrated potential harm associated with improvised balloon tamponade use In low resource settings and the World Health Organization recommends use be restricted to settings where monitoring is available and care escalation is possible. Recently, intrauterine vacuum devices have been introduced, which offer a new mechanism for achieving hemorrhage control by mechanically restoring uterine tone via vacuum suction. The Jada device, which is is FDA-cleared and commercially available in the US, found successful bleeding control in 94% of cases in an initial single-arm trial, with recent post marketing registry study described treatment success following hemorrhage in 95.8% of vaginal and 88.2% of cesarean births. Successful use of improvised vacuum devices has been described in several studies, including suction tube uterine tamponade via Levin tubing, and use of a modified Bakri balloon. Further research is needed with head-to-head comparisons of efficacy of devices and assessment of cost within the context of both device pricing and overall healthcare resource utilization.

Outcomes associated with peripartum hysterectomy in the setting of placenta accreta spectrum disorder.

BACKGROUND: Although peripartum hysterectomy for placenta accreta spectrum disorder is known to be associated with complications at the time of delivery, there are limited data on postpartum outcomes and readmission risk in this population. OBJECTIVE: This study aimed to analyze risks for adverse outcomes and postpartum readmissions in the setting of peripartum hysterectomy for placenta accreta spectrum disorder by severity of placenta accreta spectrum disorder subcategory. STUDY DESIGN: Using the 2016-2020 Nationwide Readmissions Database, this retrospective cohort study identified peripartum hysterectomies with a diagnosis of placenta accreta spectrum disorder. The primary exposure was placenta accreta spectrum disorder, subcategorized as placenta accreta vs increta/percreta. The primary outcome was readmission rate and delivery complications. Complications evaluated included the following: (1) nontransfusion severe maternal morbidity (ntSMM), (2) venous thromboembolism, (3) reoperation, (4) intraoperative complications, (5) hemorrhage, (6) sepsis, and (7) surgical site complications. We additionally evaluated delivery hospitalization and readmission mean length of stay, and hospital costs. Unadjusted and adjusted logistic regression models were fit for outcomes adjusting for clinical, demographic, and hospital factors. The association measures were expressed as unadjusted and adjusted odds ratios with 95% confidence intervals. RESULTS: Between 2016 and 2020, 7864 hysterectomies during a delivery hospitalization with a diagnosis of placenta accreta spectrum disorder were identified (66.5% with placenta accreta and 33.5% with placenta increta/percreta diagnoses). The overall 60-day all-cause readmission rate was 7.3%. Most readmissions (57.2%) occurred within 10 days of hospital discharge. Compared with peripartum hysterectomy with a diagnosis of placenta accreta, hysterectomies with placenta increta/percreta diagnoses carried significantly increased risk of 60-day readmission (adjusted odds ratio, 1.31; 95% confidence interval, 1.01-1.71), inpatient mortality (odds ratio, 13.23; 95% confidence interval, 3.35-52.30), nontransfusion severe maternal morbidity (adjusted odds ratio, 1.43; 95% confidence interval, 1.20-1.71), intraoperative complications (adjusted odds ratio, 2.31; 95% confidence interval, 1.93-2.77), and surgical site complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.23-1.95). The median length of stay during delivery hospitalization was longer for placenta increta/percreta (5.8 days; 95% confidence interval, 5.4-6.1) than for placenta accreta (4.2 days; 95% confidence interval, 4.1-4.3; P<.05). In addition, delivery hospitalization costs were higher in cases of placenta increta/percreta (median, $30,686; 95% confidence interval, $28,922-$32,449) than placenta accreta (median, $21,321; 95% confidence interval, $20,480-$22,163). CONCLUSION: Complication and readmission risks after peripartum hysterectomy with placenta accreta spectrum disorder are high. Compared with patients with placenta accreta, patients with placenta increta/percreta had increased risk for delivery and postoperative complications and postpartum readmission, and increased costs and length of stay.

Latency Period after Preterm Premature Rupture of Membranes: Singletons versus Twins.

OBJECTIVE: Several studies have evaluated the differences in duration of latency and clinical outcomes between singleton and twin pregnancies after preterm premature rupture of membranes (PPROM); however, these data are limited to single-institution analyses and based on small sample sizes. The aim of this study was to assess differences in latency and clinical outcomes in singletons versus twin gestations affected by PPROM in a large, diverse cohort of women. STUDY DESIGN: This is a secondary analysis of a multicenter trial of magnesium for neuroprotection in women at high risk of preterm birth. Our study included women with PPROM ≥ 24 weeks with singleton and twin gestations. We compared singleton versus twin gestation and our primary outcome was duration of latency after PPROM. Secondary outcomes included selected perinatal and neonatal outcomes including long-term neurodevelopmental outcomes. We fit a linear regression model to assess independent risk factors for latency duration. RESULTS: Our study included 1,753 women, 1,602 singleton gestations (91%) and 151 twin gestations (9%). The median latency period was significantly shorter in twins (4 [interquartile range, IQR: 1-10] vs. 7 [IQR: 3-16] days, p < 0.001) and gestational age at delivery was significantly earlier (29.3 vs. 30.1 weeks, p = 0.001). Twins were more likely to develop neonatal sepsis (20.1 vs. 13.4%, p = 0.004), but rates of chorioamnionitis and abruption did not differ. Twins were more likely to suffer from adverse short-term neonatal outcomes, had higher rates of neonatal demise (7.9 vs. 3.8%, p = 0.002), and had higher rates of cerebral palsy (7.3 vs. 3.7, p = 0.005). When adjusting for confounders, twin gestation remained an independent risk factor for shorter latency (p < 0.001). CONCLUSION: Twin gestations affected by PPROM had shorter latency, earlier delivery, and higher rates of short- and long-term morbidity. Despite having longer latency, singleton gestations did not have higher rates of complications associated with expectant management. KEY POINTS: · Twins affected by PPROM had shorter latency duration and earlier gestational at delivery.. · Twins with PPROM had higher rates of both short- and long-term perinatal morbidity.. · Rates of chorioamnionitis and abruption did not differ between twins and singletons with PPROM..

Preeclampsia diagnosis and management.

Preeclampsia is a severe manifestation of maternal hypertensive disease affecting 2-8% of pregnancies. The disease places women at risk of women at risk of life-threatening events, including cerebral hemorrhage, pulmonary edema, acute kidney injury, hepatic failure or rupture, disseminated intravascular coagulation, eclampsia, and placental abruption. In addition to the maternal disease burden, increased fetal morbidity and mortality occurs due to iatrogenic preterm delivery, fetal growth restriction, and placental abruption. Magnesium therapy for seizure prophylaxis and blood pressure control to limit cardiovascular and cerebrovascular morbidity are the cornerstone of treatment. Interdisciplinary planning and management are crucial to optimizing patient outcomes.

Prophylactic endovascular internal iliac balloon placement during cesarean hysterectomy for placenta accreta spectrum.

BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.

The Epidemiology of COVID-19 in Pregnancy.

As of November, 2021 there have been more than 250 million coronavirus disease-2019 (COVID-19) cases worldwide and more than 5 million deaths. Obstetric patients have been a population of interest given that they may be at risk of more severe infection and adverse pregnancy outcomes. The purpose of this review is to assess current epidemiology and outcomes research related to COVID-19 for the obstetric population. This review covers the epidemiology of COVID-19, symptomatology, transmission, and current knowledge gaps related to outcomes for the obstetric population.

Race and neonatal respiratory morbidity in the late preterm period.

BACKGROUND: Prematurity is one of the leading causes of perinatal morbidity and mortality. Some studies suggest that respiratory disease may differ by race in early preterm infants. However, the role of race in late preterm neonatal morbidity is not yet established. OBJECTIVE: The objective of our study was to determine whether neonatal respiratory morbidity differs by race in neonates born late preterm. STUDY DESIGN: This was a secondary analysis of a randomized trial of women at high risk for late preterm delivery (Antenatal Late Preterm Steroids). Our study was limited to women with nonanomalous, singleton gestations, delivering between 34+0 to 36+6 weeks. Women were categorized into 4 groups by race: Black, White, Asian, or other/mixed. The primary outcome was a neonatal composite of treatment in the first 72 hours (continuous positive airway pressure or high-flow nasal cannula >2 hours, oxygen >4 hours, extracorporeal membrane oxygenation or mechanical ventilation) or stillbirth or neonatal death before 72 hours. The secondary outcomes included severe respiratory morbidity (the primary outcome extending continuous positive airway pressure or high-flow nasal cannula to >12 continuous hours and oxygen to at least 24 continuous hours), respiratory distress syndrome, transient tachypnea of the newborn, apnea, neonatal intensive care unit admission, bronchopulmonary dysplasia, and surfactant administration. The primary and secondary outcomes were assessed in the active (steroid) and placebo groups separately. We fit a logistic regression model to adjust for confounders related to respiratory morbidity. RESULTS: Of a total of 2331 included women, 26.9% (n=627) were Black/African American, 57.1% (n=1333) White, 3.56% (n=83) Asian, and 12.36% (n=288) were other/mixed. In the placebo group, the rate of the primary outcome was significantly higher in Whites (18.6%) and Asians (22.8%) compared with the African American/Black group (12.3%) (P=.03). Adjusting for confounders, the primary outcome was not significant between the groups. The primary predictor for respiratory morbidity was a prior pregnancy with neonatal respiratory morbidity. Findings were similar in the steroid group, but severe respiratory morbidity was less common in Black infants compared with White infants (adjusted odds ratio, 0.45; 95% confidence interval, 0.24-0.83). However, a prior pregnancy with neonatal respiratory complications was no longer associated with respiratory morbidity after receipt of betamethasone. CONCLUSION: Late preterm respiratory morbidity was similar between racial groups. Although a history of pregnancy with previous neonatal respiratory disease is the strongest risk factor for recurrence, this risk factor is mitigated by the receipt of steroids.

Risk for postpartum readmissions and associated complications based on maternal age.

PURPOSE: To evaluate risk for postpartum readmissions and associated severe morbidity by maternal age. MATERIALS AND METHODS: This retrospective cohort study used the Nationwide Readmissions Database to analyze 60-day all-cause postpartum readmission risk from 2010 to 2014. Risk for severe maternal morbidity (SMM) during readmission was ascertained using criteria from the Centers for Disease Control and Prevention. The primary exposure of interest was maternal age. Outcomes included time to readmission, risk of readmission, and risk for SMM during readmission. Multivariable log linear analyses adjusting for patient, obstetric, and hospital factors were conducted to assess readmission and SMM risk with adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) as measures of effect. RESULTS: Between 2010 and 2014, we identified 15.7 million deliveries, 15% of which were to women aged 35 or older. The 60-day all-cause readmission rate was 1.7%. Of these, 13% were complicated by SMM. Age-stratification revealed that women 35 and older were at increased risk for readmission and increased risk for SMM. The majority of readmissions occurred within the first 20 days regardless of age; although, women 35 and older were more likely to be admitted within the first 10 days of discharge. Patients ages 35-39, 40-44, and >44 years had 9% (95% CI 7-10%), 37% (95% CI 34-39%), and 66% (95% CI 55-79%) significantly higher rates of postpartum readmission when compared to women age 25-29. Women 35-39, 40-44, and >44 years of age had a 15% (95% CI 10-21%), 26% (95% CI 18-34%), and 56% (95% CI 25-94%) higher risk of a readmission with SMM than women 25-29. CONCLUSIONS: AMA women are at higher risk for both postpartum readmission and severe morbidity during readmission. Women older than 35 years represent the group most likely to experience complications requiring readmission, with the highest risk age 40 and older.

Risk of Stillbirth after Antepartum Hospitalization for Hypertensive Diseases of Pregnancy.

OBJECTIVE: To determine if women with an antepartum admission for hypertensive diseases of pregnancy (HDP) were at increased risk for stillbirth. STUDY DESIGN: This study utilized the 2010 to 2014 Nationwide Readmissions Database. Antepartum admissions with HDP were identified and linked to subsequent delivery hospitalizations. Delivery hospitalizations with HDP without a preceding antepartum HDP admission were also identified. Risk for stillbirth, abruption, or both was compared between these two groups. RESULTS: An estimated 382,621 deliveries with an HDP diagnosis were identified of which 14,857 (3.9%) had a preceding antepartum admission for HDP. Stillbirth occurred in 7.8 per 1,000 delivery hospitalizations complicated by HDP with risk higher with a preceding HDP antepartum admission in both unadjusted (1.1 vs. 0.8%, risk ratios [RR] 1.46, 95% confidence interval [CI] 1.24-1.70) and adjusted (adjusted risk ratios [aRR] 1.24, 95% CI 1.06, 1.46) analyses. Abruption occurred in 19.6 per 1,000 delivery hospitalizations complicated by HDP with risk higher with a preceding HDP antepartum admission in both unadjusted (2.5 vs. 1.9%, RR 1.30, 95% CI 1.17-1.44) and adjusted (aRR 1.24, 95% CI 1.11, 1.37) analyses. Risk for combined abruption and stillbirth did not differ significantly. CONCLUSION: In this analysis, prior antenatal hospitalization was associated with increased risk for stillbirth among women with HDP.

Early CNS neurodegeneration in radiologically isolated syndrome.

OBJECTIVE: Increasing evidence indicates that the thalamus may be a location of early neurodegeneration in multiple sclerosis (MS). Our objective was to identify the presence of gray matter volume loss and thinning in patients with radiologically isolated syndrome (RIS). METHODS: Sixty-three participants were included in this case-control study. Twenty-one patients with RIS were age- and sex-matched to 42 healthy controls in a 1:2 ratio. All participants underwent brain MRIs on a single 3T scanner. After lesion segmentation and inpainting, 1 mm(3)-isometric T1-weighted images were submitted to FreeSurfer (v5.2). Normalized cortical and deep gray matter volumes were compared between patients with RIS and controls using t tests, and thalamic volumes were correlated with white matter lesion volumes using Pearson correlation. Exploratory cortical thickness maps were created. RESULTS: Although traditional normalized total gray and white matter volumes were not statistically different between patients with RIS and controls, normalized left (0.0046 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.006), right (0.0045 ± 0.0005 vs 0.0048 ± 0.0004, p = 0.008), and mean (0.0045 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.004) thalamic volumes were significantly lower in patients with RIS (n = 21, mean age 41.9 ± 12.7 years) than in controls (n = 42, mean age 41.4 ± 11.2 years). Thalamic volumes correlated modestly with white matter lesion volumes (range: r = -0.35 to -0.47). CONCLUSION: Our data provide novel evidence of thalamic atrophy in RIS and are consistent with previous reports in early MS stages. Thalamic volume loss is present early in CNS demyelinating disease and should be further investigated as a metric associated with neurodegeneration.

Why is therapeutic misconception so prevalent?

Therapeutic misconception (TM)-when clinical research participants fail to adequately grasp the difference between participating in a clinical trial and receiving ordinary clinical care-has long been recognized as a significant problem in consent to clinical trials. We suggest that TM does not primarily reflect inadequate disclosure or participants' incompetence. Instead, TM arises from divergent primary cognitive frames. The researchers' frame places the clinical trial in the context of scientific designs for assessing intervention efficacy. In contrast, most participants have a cognitive frame that is personal and focused primarily on their medical problems. To illustrate this, we draw on interview material from both clinical researchers and participants in clinical trials. We suggest that reducing TM requires encouraging subjects to adjust their frame, not just add information to their existing frame. What is necessary is a scientific reframing of participation in a clinical trial.

Alternative decision-makers' perspectives on assent and dissent for dementia research.

OBJECTIVES: Investigators generally address the ethical dilemma of patients' decisional impairment in Alzheimer disease (AD) research by obtaining consent from alternative or surrogate decision makers ("proxies") as well as assent from patients. How these proxies conceptualize patient assent, or lack of objection, to participate may influence decisions made of the patients' behalf, but has been little studied. This report examines statements of proxies relevant to how they conceptualized assent and dissent to research. DESIGN: Surveys and in-depth interviews of proxies presented with hypothetical scenario related to enrolling relatives with AD in a clinical trial of an investigational drug for AD. PARTICIPANTS: Proxies (n = 25) for people with AD. MEASUREMENTS: Open-ended and rating-scaled items assessing perspectives on enrollment in research, influences on decision-making, and willingness to override a relative's preferences regarding research participation. Statements with relevance to assent or dissent were coded. RESULTS: Proxies described looking for consistent behavioral or verbal indications of assent versus objection when trying to determine patients' preferences. However, proxies sometimes expressed willingness to override patients' desires in favor of patients' presumed best interests. The amnestic nature of the disorder led some proxies to justify overriding temporary dissent or discomfort in the interest of promoting patients' values. Patients' dependence on their caregivers for decision-making, and caregivers' awareness of their ability to persuade their relatives, also emerged in descriptions of the decision-making process. CONCLUSIONS: Proxies' statements regarding a hypothetical research enrollment decision revealed several themes with implications for the concepts of assent and dissent. Proxies may persuade or influence patients to promote the patient's best interests or values. Further work, particularly examining actual decision-making, is warranted to determine how best to operationalize the concepts of assent and dissent in the context of research involving decisionally impaired adults.

Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI.

Arterial spin labeling (ASL) perfusion MRI is a relatively novel technique that can allow for quantitative measurement of cerebral blood flow (CBF) by using magnetically labeled arterial blood water as an endogenous tracer. Available data on resting CBF in schizophrenia primarily come from invasive and expensive nuclear medicine techniques that are often limited to small samples and yield mixed results. The noninvasive nature of ASL offers promise for larger-scale studies. The utility of this approach was examined in 24 healthy controls and 30 patients with schizophrenia. Differences between groups in quantitative CBF were assessed, as were relationships between CBF and psychiatric symptoms. Group comparisons demonstrated greater CBF for controls in several regions including bilateral precuneus and middle frontal gyrus. Patients showed increased CBF in left putamen/superior corona radiata and right middle temporal gyrus. For patients, greater severity of negative symptoms was associated with reduced CBF in bilateral superior temporal gyrus, cingulate gyrus, and left middle frontal gyrus. Increased severity of positive symptoms was related to both higher CBF in cingulate gyrus and superior frontal gyrus and decreased CBF in precentral gyrus/middle frontal gyrus. These findings support the feasibility and utility of implementing ASL in schizophrenia research and expand upon previous results.

Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge.

RATIONALE: Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation. OBJECTIVES: We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia, compared to 25 control subjects without a family history of psychosis. METHODS: An oral 1 mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design, preceding identical 3 T fMRI sessions approximately 1 week apart. Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks: emotion identification and emotion memory. RESULTS: Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification, compared to equal reduction in both groups for the emotion memory task. CONCLUSIONS: GABAergic modulation with alprazolam produced differential responses in family members vs. controls, perhaps by unmasking underlying amygdalar and/or GABAergic abnormalities. Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia.

Opposing amygdala and ventral striatum connectivity during emotion identification.

Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed a well-characterized emotion identification task. As expected, the amygdala responded to THREAT (angry or fearful) faces more than NON-THREAT (sad or happy) faces. A functional connectivity analysis of the time series from an anatomically defined amygdala seed revealed a strong anticorrelation between the amygdala and the ventral striatum/ventral pallidum, consistent with an opposing role for these regions in during emotion identification. A second functional connectivity analysis (psychophysiological interaction) investigating relative connectivity on THREAT vs. NON-THREAT trials demonstrated that the amygdala had increased connectivity with the orbitofrontal cortex during THREAT trials, whereas the ventral striatum demonstrated increased connectivity with the posterior hippocampus on NON-THREAT trials. These results indicate that activity in the amygdala and ventral striatum may be inversely related, and that both regions may provide opposing affective bias signals during emotion identification.

Abnormal modulation of amygdala activity in schizophrenia in response to direct- and averted-gaze threat-related facial expressions.

OBJECTIVE: Reduced amygdala activation in individuals with schizophrenia is thought to contribute to impairments in emotion recognition and social functioning. Recent work, however, suggests that amygdala abnormalities in schizophrenia are more nuanced than generalized hypoactivation and that modulation of amygdala responses across different stimulus types may be more closely related to social functioning than to overall levels of amygdala activation during a task. The authors investigated amygdala modulation during emotion recognition in patients by manipulating the gaze direction of threat-related expressions. METHOD: Blood-oxygen-level-dependent functional MRI was used to measure neural activation in 37 healthy volunteers and 35 schizophrenia patients while participants identified the emotion (anger or fear) displayed on facial stimuli that appeared with either direct or averted gaze. RESULTS: Analysis of percent signal change in the amygdala bilaterally revealed a three-way interaction of emotion, gaze, and group, demonstrating significantly reduced amygdala responses to direct-gaze anger expressions in the patient group but comparable levels of activation across groups in all other conditions. Within the patient group, amygdala responses to direct-gaze anger expressions were positively correlated with level of functioning. CONCLUSIONS: These findings extend previous reports of amygdala hypoactivation in schizophrenia by identifying abnormal amygdala modulation in response to varying emotional stimuli. Additionally, the strong relationship between amygdala activation and social and occupational functioning underscores the need for investigations of amygdala modulation in schizophrenia that further specify the nature of these impairments and that examine a potential causal link between amygdala activation and functioning.

Looking for meaning: eye movements are sensitive to overlapping semantic features, not association.

Theories of semantic memory differ in the extent to which relationships among concepts are captured via associative or via semantic relatedness. We examined the contributions of these two factors, using a visual world paradigm in which participants selected the named object from a four-picture display. We controlled for semantic relatedness while manipulating associative strength by using the visual world paradigm's analogue to presenting asymmetrically associated pairs in either their forward or backward associative direction (e.g., ham-eggs vs. eggs-ham). Semantically related objects were preferentially fixated regardless of the direction of presentation (and the effect size was unchanged by presentation direction). However, when pairs were associated but not semantically related (e.g., iceberg-lettuce), associated objects were not preferentially fixated in either direction. These findings lend support to theories in which semantic memory is organized according to semantic relatedness (e.g., distributed models) and suggest that association by itself has little effect on this organization.