BACKGROUNDThere is a substantial history studying the relationship between general intelligence and the core symptoms of autism. However, a gap in knowledge is how dimensional autism symptomatology ...associates with different components of clinically-relevant hierarchical models of intelligence.METHODWe examined correlations between autism diagnostic symptom magnitude (Autism Diagnostic Observational Schedule; ADOS) and a hierarchical statistical model of intelligence. One autistic cohort was tested on the fourth edition of Wechsler Intelligence Scale for Children (WISC-IV; N = 131), and another on the fifth edition (WISC-V; N = 83). We anticipated a convergent pattern of results between cohorts.RESULTSOn WISC-IV, ADOS scores were correlated significantly with g and three out of four intermediate factor scores, which was a broader pattern of correlations than anticipated from the literature. In the WISC-V cohort, only one intermediate factor correlated significantly with the ADOS; correlations with g and the other intermediate factors were less statistically certain. ADOS-factor correlations were larger in the WISC-IV than WISC-V cohort; this difference was significant at the 90% level.CONCLUSIONSWISC-IV shows dimensional relationships with ADOS at multiple points in the hierarchical model of intelligence. Moreover, the current results provide evidence that relationship between core autism symptomatology and the construct of general intelligence may depend on how intelligence is measured. Known cohort effects in the relationship between categorical autism diagnosis and general intelligence have previously been attributed to changes in autism diagnostic practices. To our knowledge, this is the first evidence that differing versions of IQ tests may be implicated.
CONTEXT More than 6000 healthy US individuals every year undergo nephrectomy for the purposes of live donation; however, safety remains in question because longitudinal outcome studies have occurred ...at single centers with limited generalizability. OBJECTIVES To study national trends in live kidney donor selection and outcome, to estimate short-term operative risk in various strata of live donors, and to compare long-term death rates with a matched cohort of nondonors who are as similar to the donor cohort as possible and as free as possible from contraindications to live donation. DESIGN, SETTING, AND PARTICIPANTS Live donors were drawn from a mandated national registry of 80 347 live kidney donors in the United States between April 1, 1994, and March 31, 2009. Median (interquartile range) follow-up was 6.3 (3.2-9.8) years. A matched cohort was drawn from 9364 participants of the third National Health and Nutrition Examination Survey (NHANES III) after excluding those with contraindications to kidney donation. MAIN OUTCOME MEASURES Surgical mortality and long-term survival. RESULTS There were 25 deaths within 90 days of live kidney donation during the study period. Surgical mortality from live kidney donation was 3.1 per 10 000 donors (95% confidence interval CI, 2.0-4.6) and did not change during the last 15 years despite differences in practice and selection. Surgical mortality was higher in men than in women (5.1 vs 1.7 per 10 000 donors; risk ratio RR, 3.0; 95% CI, 1.3-6.9; P = .007), in black vs white and Hispanic individuals (7.6 vs 2.6 and 2.0 per 10 000 donors; RR, 3.1; 95% CI, 1.3-7.1; P = .01), and in donors with hypertension vs without hypertension (36.7 vs 1.3 per 10 000 donors; RR, 27.4; 95% CI, 5.0-149.5; P < .001). However, long-term risk of death was no higher for live donors than for age- and comorbidity-matched NHANES III participants for all patients and also stratified by age, sex, and race. CONCLUSION Among a cohort of live kidney donors compared with a healthy matched cohort, the mortality rate was not significantly increased after a median of 6.3 years.
•Rats that are susceptible and resistant to weight loss during activity-based anorexia exhibit distinct running patterns.•Resistant animals allocate a higher percentage of their running to food ...anticipatory activity both prior to and during activity-based anorexia.•Susceptible animals run more overall and during the dark cycle than resistant animals.
Individuals with anorexia nervosa (AN) exhibit dangerous weight loss due to restricted eating and hyperactivity. Those with AN are predominantly women and most cases have an age of onset during adolescence. Activity-based anorexia (ABA) is a rodent behavioral paradigm that recapitulates many of the features of AN including restricted food intake and hyperactivity, resulting in precipitous weight loss. In addition, there is enhanced sensitivity to the paradigm during adolescence. In ABA, animals are given time-restricted access to food and unlimited access to a running wheel. Under these conditions, most animals increase their running and decrease their food intake resulting in precipitous weight loss until they either die or researchers discontinue the paradigm. Some animals learn to balance their food intake and energy expenditure and are able to stabilize and eventually reverse their weight loss. For these studies, adolescent (postnatal day 33–42), female Sprague Dawley (n = 68) rats were placed under ABA conditions (unlimited access to a running wheel and 1.5 hrs access to food) until they either reached 25% body weight loss or for 7 days. 70.6% of subjects reached 25% body weight loss before 7 days and were designated susceptible to ABA while 29.4% animals were resistant to the paradigm and did not achieve the weight loss criterion. We used discrete time survival analysis to investigate the contribution of food intake and running behavior during distinct time periods both prior to and during ABA to the likelihood of reaching the weight loss criterion and dropping out of ABA. Our analyses revealed risk factors, including total running and dark cycle running, that increased the likelihood of dropping out of the paradigm, as well as protective factors, including age at the start of ABA, the percent of total running exhibited as food anticipatory activity (FAA), and food intake, that reduced the likelihood of dropping out. These measures had predictive value whether taken before or during exposure to ABA conditions. Our findings suggest that certain running and food intake behaviors may be indicative of a phenotype that predisposes animals to susceptibility to ABA. They also provide evidence that running during distinct time periods may reflect functioning of distinct neural circuitry and differentially influence susceptibility and resistance to the paradigm.
SUMMARY
Mediation analysis is an important tool in the behavioral sciences for investigating the role of intermediate variables that lie in the path between a treatment and an outcome variable. The ...influence of the intermediate variable on the outcome is often explored using a linear structural equation model (LSEM), with model coefficients interpreted as possible effects. While there has been significant research on the topic, little work has been done when the intermediate variable (mediator) is a high-dimensional vector. In this work, we introduce a novel method for identifying potential mediators in this setting called the directions of mediation (DMs). DMs linearly combine potential mediators into a smaller number of orthogonal components, with components ranked based on the proportion of the LSEM likelihood each accounts for. This method is well suited for cases when many potential mediators are measured. Examples of high-dimensional potential mediators are brain images composed of hundreds of thousands of voxels, genetic variation measured at millions of single nucleotide polymorphisms (SNPs), or vectors of thousands of variables in large-scale epidemiological studies. We demonstrate the method using a functional magnetic resonance imaging study of thermal pain where we are interested in determining which brain locations mediate the relationship between the application of a thermal stimulus and self-reported pain.
A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although ...some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain–behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.
► Network development leads to specific changes between children and adults. ► Adults have stronger within-network connectivity to circumscribed regions. ► Adults have more anticorrelated between-network connectivity to circumscribed regions. ► Inhibitory control is related to the strength of anticorrelation in developing areas.
The Wechsler Intelligence Scale for Children (WISC) employs a hierarchical model of general intelligence in which index scores separate out different clinically-relevant aspects of intelligence; the ...test is designed such that index scores are statistically independent from one another within the normative sample. Whether or not the existing index scores meet the desired psychometric property of being statistically independent within autistic samples is unknown.
We conducted a factor analysis on WISC fifth edition (WISC-V) (N = 83) and WISC fourth edition (WISC-IV) (N = 131) subtest data in children with autism. We compared the data-driven exploratory factor analysis with the manual-derived index scores, including in a typically developing (TD) WISC-IV cohort (N = 209).
The WISC-IV TD cohort showed the expected 1:1 relationship between empirically derived factors and manual-derived index scores. We observed less unique correlations between our data-driven factors and manualized IQ index scores in both ASD samples (WISC-IV and WISC-V). In particular, in both WISC-IV and -V, working memory (WM) influenced index scores in autistic individuals that do not load on WM in the normative sample.
WISC index scores do not show the desired statistical independence within autistic samples, as judged against an empirically-derived exploratory factor analysis. In particular, within the currently used WISC-V version, WM influences multiple index scores.
•Current methods for assessing mediation do not easily extend to high dimensions.•We introduce a new approach for performing high-dimensional mediation analysis.•Links high-dimensional mediator to ...path analysis model via machine learning algorithm.•Method illustrated using data from two fMRI studies.
Mediation analysis is used to investigate the role of intermediate variables (mediators) that lie in the path between an exposure and an outcome variable. While significant research has focused on developing methods for assessing the influence of mediators on the exposure-outcome relationship, current approaches do not easily extend to settings where the mediator is high-dimensional. These situations are becoming increasingly common with the rapid increase of new applications measuring massive numbers of variables, including brain imaging, genomics, and metabolomics. In this work, we introduce a novel machine learning based method for identifying high dimensional mediators. The proposed algorithm iterates between using a machine learning model to map the high-dimensional mediators onto a lower-dimensional space, and using the predicted values as input in a standard three-variable mediation model. Hence, the machine learning model is trained to maximize the likelihood of the mediation model. Importantly, the proposed algorithm is agnostic to the machine learning model that is used, providing significant flexibility in the types of situations where it can be used. We illustrate the proposed methodology using data from two functional Magnetic Resonance Imaging (fMRI) studies. First, using data from a task-based fMRI study of thermal pain, we combine the proposed algorithm with a deep learning model to detect distributed, network-level brain patterns mediating the relationship between stimulus intensity (temperature) and reported pain at the single trial level. Second, using resting-state fMRI data from the Human Connectome Project, we combine the proposed algorithm with a connectome-based predictive modeling approach to determine brain functional connectivity measures that mediate the relationship between fluid intelligence and working memory accuracy. In both cases, our multivariate mediation model links exposure variables (thermal pain or fluid intelligence), high dimensional brain measures (single-trial brain activation maps or resting-state brain connectivity) and behavioral outcomes (pain report or working memory accuracy) into a single unified model. Using the proposed approach, we are able to identify brain-based measures that simultaneously encode the exposure variable and correlate with the behavioral outcome.
Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns.
To define the safety of a protocol for MRI at the commonly used magnetic ...strength of 1.5 T in patients with implanted cardiac devices.
Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the United States (94% of examinations) and one in Israel.
438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies.
Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist.
Activation or inhibition of pacing, symptoms, and device variables.
In 3 patients (0.7% 95% CI, 0% to 1.5%), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV interquartile range {IQR}, -0.7 to 0 V) and atrial and right and left ventricular lead impedances (median change, -2 Ω IQR, -13 to 0 Ω, -4 Ω IQR, -16 to 0 Ω, and -11 Ω IQR, -40 to 0 Ω, respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, IQR, -1.1 to 0.3 mV), decreased RV lead impedance (median, -3 Ω, IQR, -29 to 15 Ω), increased RV capture threshold (median, 0 V, IQR, 0 to 0.2 Ω), and decreased battery voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming.
Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed.
With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential.
Adolescents who are clinically recovered from concussion continue to show subtle motor impairment on neurophysiological and behavioral measures. However, there is limited information on ...brain–behavior relationships of persistent motor impairment following clinical recovery from concussion. We examined the relationship between subtle motor performance and functional connectivity of the brain in adolescents with a history of concussion, status post‐symptom resolution, and subjective return to baseline. Participants included 27 adolescents who were clinically recovered from concussion and 29 never‐concussed, typically developing controls (10–17 years); all participants were examined using the Physical and Neurologic Examination of Subtle Signs (PANESS). Functional connectivity between the default mode network (DMN) or dorsal attention network (DAN) and regions of interest within the motor network was assessed using resting‐state functional magnetic resonance imaging (rsfMRI). Compared to controls, adolescents clinically recovered from concussion showed greater subtle motor deficits as evaluated by the PANESS and increased connectivity between the DMN and left lateral premotor cortex. DMN to left lateral premotor cortex connectivity was significantly correlated with the total PANESS score, with more atypical connectivity associated with more motor abnormalities. This suggests that altered functional connectivity of the brain may underlie subtle motor deficits in adolescents who have clinically recovered from concussion. More investigation is required to understand the persistence and longer‐term clinical relevance of altered functional connectivity and associated subtle motor deficits to inform whether functional connectivity may serve as an important biomarker related to longer‐term outcomes after clinical recovery from concussion.
This study examined functional connectivity and subtle motor deficits in adolescents clinically recovered from a concussion. Compared to never‐injured controls, adolescents clinically recovered from concussion showed greater subtle motor deficits and increased connectivity between the default mode network (DMN) and left lateral premotor cortex. DMN to left lateral premotor cortex connectivity significantly correlated with the total PANESS score, with more atypical connectivity associated with more motor abnormalities.
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