Faculty Bibliography

We address the issue of reliably detecting and quantifying cross-frequency coupling (CFC) in neural time series. Based on non-linear auto-regressive models, the proposed method provides a generative and parametric model of the time-varying spectral content of the signals. As this method models the entire spectrum simultaneously, it avoids the pitfalls related to incorrect filtering or the use of the Hilbert transform on wide-band signals. As the model is probabilistic, it also provides a score of the model "goodness of fit" via the likelihood, enabling easy and legitimate model selection and parameter comparison; this data-driven feature is unique to our model-based approach. Using three datasets obtained with invasive neurophysiological recordings in humans and rodents, we demonstrate that these models are able to replicate previous results obtained with other metrics, but also reveal new insights such as the influence of the amplitude of the slow oscillation. Using simulations, we demonstrate that our parametric method can reveal neural couplings with shorter signals than non-parametric methods. We also show how the likelihood can be used to find optimal filtering parameters, suggesting new properties on the spectrum of the driving signal, but also to estimate the optimal delay between the coupled signals, enabling a directionality estimation in the coupling.

Reports an error in "The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5" by Berk Ustun, Lenard A. Adler, Cynthia Rudin, Stephen V. Faraone, Thomas J. Spencer, Patricia Berglund, Michael J. Gruber and Ronald C. Kessler (JAMA Psychiatry, 2017[May], Vol 74[5], 520-526). In the original article, there was an error in the Results section of the article. In the second paragraph of "Choosing the Optimal Number of Screening Questions," option 3 included the phrase "Criterion A2e, acts as if 'driven by a motor.'" The phrase should have been "Criterion A2d, difficulty playing quietly/leisure time." (The following abstract of the original article appeared in record 2017-32659-009). Importance: Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria. Objectives: To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization Adult ADHD Self-Report Scale (ASRS) for screening. Design, setting, and participants: Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016. Main outcomes and measures: The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS. Results: Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%). Conclusions and relevance: The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

Disgust is a core emotion evolved to detect and avoid the ingestion of poisonous food as well as the contact with pathogens and other harmful agents. Previous research has shown that multisensory presentation of olfactory and visual information may strengthen the processing of disgust-relevant information. However, it is not known whether these findings extend to dynamic facial stimuli that changes from neutral to emotionally expressive, or if individual differences in trait body odor disgust may influence the processing of disgust-related information. In this preregistered study, we tested whether a classification of dynamic facial expressions as happy or disgusted, and an emotional evaluation of these facial expressions, would be affected by individual differences in body odor disgust sensitivity, and by exposure to a sweat-like, negatively valenced odor (valeric acid), as compared with a soap-like, positively valenced odor (lilac essence) or a no-odor control. Using Bayesian hypothesis testing, we found evidence that odors do not affect recognition of emotion in dynamic faces even when body odor disgust sensitivity was used as moderator. However, an exploratory analysis suggested that an unpleasant odor context may cause faster RTs for faces, independent of their emotional expression. Our results further our understanding of the scope and limits of odor effects on facial perception affect and suggest further studies should focus on reproducibility, specifying experimental circumstances where odor effects on facial expressions may be present versus absent.

A remarkable example of maladaptive plasticity is the development of epilepsy after a brain insult or injury to a normal animal or human. A structure that is considered central to the development of this type of epilepsy is the dentate gyrus (DG), because it is normally a relatively inhibited structure and its quiescence is thought to reduce hippocampal seizure activity. This characteristic of the DG is also considered to be important for normal hippocampal-dependent cognitive functions. It has been suggested that the brain insults which cause epilepsy do so because they cause the DG to be more easily activated. One type of brain insult that is commonly used is induction of severe seizures (status epilepticus; SE) by systemic injection of a convulsant drug. Here we describe an alteration in the DG after this type of experimental SE that may contribute to chronic seizures that has not been described before: large folds or gyri that develop in the DG by 1 month after SE. Large gyri appeared to increase network excitability because epileptiform discharges recorded in hippocampal slices after SE were longer in duration when recorded inside gyri relative to locations outside gyri. Large gyri may also increase excitability because immature adult-born neurons accumulated at the base of gyri with time after SE, and previous studies have suggested that abnormalities in adult-born DG neurons promote seizures after SE. In summary, large gyri after SE are a common finding in adult rats, show increased excitability, and are associated with the development of an abnormal spatial distribution of adult-born neurons. Together these alterations may contribute to chronic seizures and associated cognitive comorbidities after SE.

OBJECTIVE:To examine the association between 9/11-related exposures and self-reported hearing problems among 16,579 rescue/recovery workers in the World Trade Center (WTC) Health Registry. METHODS:Using Registry Waves 1 (2003 to 2004) and 2 (2006 to 2007), we modeled the association between two metrics of 9/11-related exposures and hearing difficulties. RESULTS:The prevalence of incident, persistent hearing problems was 4.4%. In a fully adjusted model, workers with higher environmental hazards scores were twice as likely (interquartile range OR 2.1; 95% confidence interval [CI] 1.8, 2.5) to report hearing problems. Based on the same fully adjusted model, workers unable to hear in the dust cloud were 2.3 (95% CI 1.8, 3.0) times more likely to report hearing problems as compared with workers not in the dust cloud. CONCLUSIONS:We observed a consistent association between WTC-related exposures and self-reported hearing problems among rescue/recovery workers.

BACKGROUND:The Affordable Care Act of 2010 advanced the economic model of bundled payments for total joint arthroplasty (TJA), in which hospitals will be financially responsible for readmissions, typically at 90 days after surgery. However, little is known about the financial burden of readmissions and what patient, clinical, and hospital factors drive readmission costs. QUESTIONS/PURPOSES/OBJECTIVE:(1) What is the incidence, payer mix, and demographics of THA and TKA readmissions in the United States? (2) What patient, clinical, and hospital factors are associated with the cost of 30- and 90-day readmissions after primary THA and TKA? (3) Are there any differences in the economic burden of THA and TKA readmissions between payers? (4) What types of THA and TKA readmissions are most costly to the US hospital system? METHODS:The recently developed Nationwide Readmissions Database from the Healthcare Cost and Utilization Project (2006 hospitals from 21 states) was used to identify 719,394 primary TJAs and 62,493 90-day readmissions in the first 9 months of 2013 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. We classified the reasons for readmissions as either procedure- or medical-related. Cost-to-charge ratios supplied with the Nationwide Readmissions Database were used to compute the individual per-patient cost of 90-day readmissions as a continuous variable in separate general linear models for THA and TKA. Payer, patient, clinical, and hospital factors were treated as covariates. We estimated the national burden of readmissions by payer and by the reason for readmission. RESULTS:The national rates of 30- and 90-day readmissions after THA were 4% (95% confidence interval [CI], 4.2%-4.5%) and 8% (95% CI, 7.5%-8.1%), respectively. The national rates of 30- and 90-day readmissions after primary TKA were 4% (95% CI, 3.8%-4.0%) and 7% (95% CI, 6.8%-7.2%), respectively. The five most important variables responsible for the cost of 90-day THA readmissions (in rank order, based on the Type III F-statistic, p < 0.001) were length of stay (LOS), all patient-refined diagnosis-related group (APR DRG) severity, type of readmission (that is, medical- versus procedure-related), hospital ownership, and age. Likewise, the five most important variables responsible for the cost of 90-day TKA readmissions were LOS, APR DRG severity, gender, hospital procedure volume, and hospital ownership. After adjusting for covariates, mean 90-day readmission costs reimbursed by private insurance were, on average, USD 1324 and USD 1372 greater than Medicare (p < 0.001) for THA and TKA, respectively. In the 90 days after TJA, two-thirds of the total annual readmission costs were covered by Medicare. In 90 days after THA, more readmissions were still associated with procedure-related complications, including infections, dislocations, and periprosthetic fractures, which in aggregate account for 59% (95% CI, 59.1%-59.6%) of the total readmission costs to the US healthcare system. For TKA, 49% of the total readmission cost (95% CI, 48.8%-49.6%) in 90 days for the United States was associated with procedure issues, most notably including infections. CONCLUSIONS:Hospital readmissions up to 90 days after TJA represent a massive economic burden on the US healthcare system. Approximately half of the total annual economic burden for readmissions in the United States is medical and unrelated to the joint replacement procedure and half is related to procedural complications. CLINICAL RELEVANCE/CONCLUSIONS:This national study underscores LOS during readmission as a primary cost driver, suggesting that hospitals and doctors further optimize, to the extent possible, the clinical pathways for the hospitalization of readmitted patients. Because patients readmitted as a result of infection, dislocation, and periprosthetic fractures are the most costly types of readmissions, efforts to reduce the LOS for these types of readmissions will have the greatest impact on their economic burden. Additional clinical research is needed to determine the extent to which, if any, the LOS during readmissions can be reduced without sacrificing quality or access of care.

OBJECTIVE:Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). METHOD/METHODS:Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. RESULTS:After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). CONCLUSION/CONCLUSIONS:BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.

What do infants learn when they learn to sit upright? We tested behavioral flexibility in learning to sit-the ability to adapt posture to changes in the environment-in 6- to 9-month-old infants sitting on forward and backward slopes. Infants began with slant at 0°; then slant increased in 2° increments until infants lost balance. Infants kept balance on impressively steep slopes, especially in the forward direction, despite the unexpected movements of the apparatus. Between slant adjustments while the slope was stationary, infants adapted posture to the direction and degree of slant by leaning backward on forward slopes and forward on backward slopes. Postural adaptations were nearly optimal for backward slopes. Sitting experience predicted greater postural adaptations and increased ability to keep balance on steeper changes of slant, but only for forward slopes. We suggest that behavioral flexibility is integral to learning to sit and increases with sitting experience.

Cat-scratch disease-associated vertebral osteomyelitis and epidural involvement are rare and may manifest with nonspecific chronic symptoms in children, such as fever or torticollis. We present only the fourth case in the literature describing epidural involvement in an immunocompetent boy presenting with fever, torticollis, and indiscriminate left upper back tenderness. Bartonella henselae serologies are important to consider because such atypical complications often are responsive to conservative management with antibiotics.