Gonocyte transformation in congenital undescended testes: what is the role of inhibin-B in cell death?

PURPOSE: Undescended testes (UDT) are subjected to heat stress, which can disturb gonocyte transformation as well as apoptosis. This study aims to describe the apoptosis pathway occurring during minipuberty of children with unilateral (UDT), and to investigate the role of inhibin-B. METHODS: Testicular biopsies at unilateral orchidopexy of 10 boys (6-9 months old) with normal inhibin-B (n = 5) or low inhibin-B (n = 5) were selected for immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling) assay. Testicular tubules were labelled with antibodies against Anti-Müllerian hormone (AMH, Sertoli cell marker), mouse Vasa Homolog (MVH) and placental alkaline phosphatase (PLAP) (both germ cell markers), cleaved caspase3 (apoptotic marker), and followed by confocal imaging and cell counting with Fiji/ImageJ. Data were analyzed with GraphPad Prism. RESULTS: In males with low and normal inhibin-B, there was no statistical difference (p > 0.05) in the percentage of testicular tubules containing TUNEL + cells, number of cleaved caspase3 ± germ cells/tubule, total number of germ cells/tubule, and the percentage of fibrotic tubules or number of Sertoli cells/tubule. CONCLUSIONS: These results suggest that inhibin-B does not regulate cell death of gonocytes and further studies are required to uncover any role of inhibin-B in gonocyte transformation.

Executive function deficits and glutamatergic protein alterations in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine-1 receptor and vesicular glutamate transporter (VGLUT)-1 expression increased in the mPFC following DA loss. There were significant MPTP-induced decreases and increases in VGLUT-1 and VGLUT-2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical-cortical (VGLUT-1) glutamate function but also in striatal DA and glutamate (VGLUT-1/VGLUT-2) input.

A universal preference for animate agents in hominids.

When conversing, humans instantaneously predict meaning from fragmentary and ambiguous mspeech, long before utterance completion. They do this by integrating priors (initial assumptions about the world) with contextual evidence to rapidly decide on the most likely meaning. One powerful prior is attentional preference for agents, which biases sentence processing but universally so only if agents are animate. Here, we investigate the evolutionary origins of this preference, by allowing chimpanzees, gorillas, orangutans, human children, and adults to freely choose between agents and patients in still images, following video clips depicting their dyadic interaction. All participants preferred animate (and occasionally inanimate) agents, although the effect was attenuated if patients were also animate. The findings suggest that a preference for animate agents evolved before language and is not reducible to simple perceptual biases. To conclude, both humans and great apes prefer animate agents in decision tasks, echoing a universal prior in human language processing.

Does the primate face cue personality?

When looking at others, primates primarily focus on the face - detecting the face first and looking at it longer than other parts of the body. This is because primate faces, even without expression, convey trait information crucial for navigating social relationships. Recent studies on primates, including humans, have linked facial features, specifically facial width-to-height ratio (fWHR), to rank and Dominance-related personality traits, suggesting these links' potential role in social decisions. However, studies on the association between dominance and fWHR report contradictory results in humans and variable patterns in nonhuman primates. It is also not clear whether and how nonhuman primates perceive different facial cues to personality traits and whether these may have evolved as social signals. This review summarises the variable facial-personality links, their underlying proximate and evolutionary mechanisms and their perception across primates. We emphasise the importance of employing comparative research, including various primate species and human populations, to disentangle phylogeny from socio-ecological drivers and to understand the selection pressures driving the facial-personality links in humans. Finally, we encourage researchers to move away from single facial measures and towards holistic measures and to complement perception studies using neuroscientific methods.

The use of gaze to study cognition: limitations, solutions, and applications to animal welfare.

The study of gaze responses, typically using looking time paradigms, has become a popular approach to improving our understanding of cognitive processes in non-verbal individuals. Our interpretation of data derived from these paradigms, however, is constrained by how we conceptually and methodologically approach these problems. In this perspective paper, we outline the application of gaze studies in comparative cognitive and behavioral research and highlight current limitations in the interpretation of commonly used paradigms. Further, we propose potential solutions, including improvements to current experimental approaches, as well as broad-scale benefits of technology and collaboration. Finally, we outline the potential benefits of studying gaze responses from an animal welfare perspective. We advocate the implementation of these proposals across the field of animal behavior and cognition to aid experimental validity, and further advance our knowledge on a variety of cognitive processes and welfare outcomes.

The evolutionary origins of syntax: Event cognition in nonhuman primates.

Languages tend to encode events from the perspective of agents, placing them first and in simpler forms than patients. This agent bias is mirrored by cognition: Agents are more quickly recognized than patients and generally attract more attention. This leads to the hypothesis that key aspects of language structure are fundamentally rooted in a cognition that decomposes events into agents, actions, and patients, privileging agents. Although this type of event representation is almost certainly universal across languages, it remains unclear whether the underlying cognition is uniquely human or more widespread in animals. Here, we review a range of evidence from primates and other animals, which suggests that agent-based event decomposition is phylogenetically older than humans. We propose a research program to test this hypothesis in great apes and human infants, with the goal to resolve one of the major questions in the evolution of language, the origins of syntax.

Comparison of Angiographic and Intravascular Ultrasound Vessel Measurements in Infra-Popliteal Endovascular Interventions: The Below-the-Knee Calibration Study.

BACKGROUND: Endovascular revascularization (ER) via percutaneous transluminal angioplasty (PTA) and stenting are viable options for revascularization in below-the-knee (BTK) peripheral arterial disease. Two-dimensional angiography has been the standard of practice for estimating vessel size and selecting treatment devices during ER. However, in other vascular territories, intravascular ultrasound (IVUS) offers better visualization of the lumen dimensions. PURPOSE: To compare angiographic and intravascular ultrasound reference vessel (lumen) measurements in below-the-knee peripheral artery interventions. METHODS: Twenty consecutive patients were enrolled in the BTK Calibration study from 2 sites in the United States and Australia. Patients with at least one diseased segment in a native infra-popliteal artery (below-the-knee) and a clinical indication for endovascular therapy (EVT) were included with no limitations with regard to vessel diameter or lesion length. Digital subtraction angiography and IVUS imaging were collected pre- and post-PTA and images were sent to an independent core lab for standardized quantitative analysis of the normal-looking reference vessel dimensions when available. The results were presented as least square means with 95% confidence intervals and a p-value of <0.05 was considered significant. RESULTS: The overall (N = 19) mean reference vessel diameter for QVA was 2.98 ± 1.24 mm vs. 3.47 ± 0.72 mm for IVUS (mean difference was -0.50 mm, (95% CI: -0.80, -0.20; p = 0.14). As expected, in the proximal segments (N = 12), the mean reference vessel diameters were larger: for QVA, it was 3.17 ± 1.34 mm vs. 3.55 ± 0.76 mm in IVUS, (mean difference was -0.38 mm, (95% CI: -0.79, 0.03; p = 0.40); while in the distal segments (N = 7), mean reference vessel diameters were smaller: for QVA, it was 2.64 ± 1.06 mm vs. 3.33 ± 0.67 mm in IVUS, (mean difference was -0.69 mm, (95% CI: -1.04, 0.34; p = 0.17). We observed a greater degree of acute gain in cases where the treatment balloon size correlated with the IVUS measured reference size. CONCLUSION: Angiography underestimates infrapopliteal reference vessel lumen size even when quantitatively assessed. Adjunctive IVUS imaging use in guiding BTK procedures could help ensure adequate sizing and possibly impact immediate post-procedure indices.

Delay discounting of reward in ADHD: application in young children.

BACKGROUND: A key underlying process that may contribute to attention-deficit/hyperactivity disorder (ADHD) involves alterations in reward evaluation, including assessing the relative value of immediate over delayed rewards. This study examines whether children with ADHD discount the value of delayed rewards to a greater degree than typically developing children using a delay discounting task. METHODS: Children aged 7-9 years diagnosed with ADHD and controls completed a task in which they chose between a hypothetical $10 available after a delay (7, 30, 90 and 180 days) versus various amounts available immediately. RESULTS: ADHD participants discounted more steeply than controls. However, this effect did not survive covarying of IQ. CONCLUSIONS: ADHD is associated with a steeper delay gradient when contemplating hypothetical later rewards, but not independently of IQ. The interplay of cognitive processing and IQ with reward evaluation in ADHD requires further exploration.

Mortality rate comparison after switching from continuous to prolonged intermittent renal replacement for acute kidney injury in three intensive care units from different countries.

BACKGROUND: Prolonged intermittent renal replacement therapy (PIRRT) is a dialysis modality for critically ill patients that in theory combines the superior detoxification and haemodynamic stability of the continuous renal replacement therapy (CRRT) with the operational convenience, reduced haemorrhagic risk and low cost of conventional intermittent haemodialysis. However, the extent to which PIRRT should replace these other modalities is uncertain because comparative studies of mortality are lacking. We retrospectively examined the mortality data from three general intensive care units (ICUs) in different countries that have switched their predominant therapeutic approach from CRRT to PIRRT. We assessed whether this practice change was associated with a change in mortality rate. METHODS: Data were analysed from ICUs in New Zealand, Australia and Italy. The study population comprised all patients requiring renal replacement therapy from 1 January 1995 to 31 December 2005 (n = 1347), the period of time spanning the change from CRRT to PIRRT in each unit. Poisson regression models were used to estimate the incident rate ratio (IRR) for death, comparing the periods before and after change to PIRRT in each unit. Estimates were adjusted for patient illness severity (APACHE II score) and for the underlying time trend in mortality rate over time. RESULTS: The change from CRRT to PIRRT was not associated with any increase in mortality rate, with an adjusted IRR of 1.02 (0.61-1.71). The IRR was virtually identical in the three ICUs (P-value = 0.63 for the difference in the IRR between ICUs). CONCLUSIONS: Switching from CRRT to PIRRT was not associated with a change in mortality rate. Pending the results of a randomized trial, our study provides evidence that PIRRT might be equivalent to CRRT in the general ICU patient.

Early social rearing, the V1A arginine vasopressin receptor genotype, and autistic traits in chimpanzees.

Previous studies found associations between autism-related phenotypes and both rearing and V1A arginine vasopressin receptor (AVPR1A) genotypes. We tested whether these exposures as well as their interaction were associated with autism-related phenotypes in 121 laboratory-housed chimpanzees. We used expert-derived weights to obtain autism scores from ratings on the 43-item Chimpanzee Personality Questionnaire; higher scores indicated more autistic-like traits. The first model included fixed effects for sex, age, and rearing, and a random effect that addressed the relatedness of subjects. The second model was the same except that it also included the rearing × AVPR1A genotype interaction as a fixed effect. Both models indicated that the phenotype was moderately heritable and that chimpanzees reared by their mothers had lower scores on the scale. The effect of genotype in both models indicated that chimpanzees with an indel deletion had higher scores on the scale, although the credible interval included zero. Moreover, the rearing × genotype interaction in the second model indicated that chimpanzees who possessed the non-deletion genotype and who were reared by their mother were at even greater risk. The credible interval for this effect did not include zero, but fit statistics indicated that the model without the interaction was marginally better, and the interaction was in the opposite direction than we expected based on previous work. These findings highlight the importance of rearing effects in the typical social development of our closet-living nonhuman relative. LAY SUMMARY: We tested whether, in chimpanzees, scores on a scale comprising traits that resembled aspects of autism were related to a gene associated with autism in prior research and/or early rearing. Human-reared chimpanzees had higher scores (indicating more autistic-like traits). Chimpanzees that possessed the gene also had higher scores, but we could not exclude the possibility that there was no effect of genotype. These findings suggest that we can measure autism-like characteristics in chimpanzees, and so study it in this species.

Comparison of Patterns of Coronary Artery Disease in Patients With Heart Failure by Cardiac Amyloidosis Status.

BACKGROUND/PURPOSE: The aim of this study is to characterize the pattern and the severity of coronary artery lesions in cardiac amyloidosis. METHODS: We retrospectively compared patients with heart failure who tested positive (i.e., biopsy or gene tests - HF/CA+) against those who tested negative (HF/CA-) for cardiac amyloidosis. Groups were compared demographically and angiographically for qualitative and quantitative variables to determine patterns of involvement in the major epicardial coronary vessels. RESULTS: The study included 110 heart failure patients, of whom 55 patients (88 lesions) were in the HF/CA+ group, and 55 patients (66 lesions) were HF/CA-. Despite the advanced age of HF/CA+ patients (74.5 ± 11.0 years vs. 54.1 ± 15.0 years; p = 0.05), no severe calcification was found in the HF/CA+ group (0.0% vs. 4.5%; p = 0.018). The HF/CA+ group also had fewer ostial lesions (3.4% vs. 15.1%; p = 0.0095) and a higher, albeit not significant, Thrombolysis in Myocardial Infarction frame count (30.4 ± 12.6 vs. 26.6 ± 11 frames; p = 0.06). In the HF/CA+ group, men had a significant number of tandem lesions compared to women (14.5% vs 0.0%, p = 0.02). CONCLUSIONS: Overall, heart failure patients with cardiac amyloidosis were older but were found to have less calcified lesions, less ostial involvement, and a reduced anterograde coronary blood flow. This is the first report examining coronary lesions in heart failure patients with cardiac amyloidosis.

Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.

BACKGROUND: The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. METHODS/DESIGN: Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.

Macaque Gaze Responses to the Primatar: A Virtual Macaque Head for Social Cognition Research.

Following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. They allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. In using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and induce an aversion response. At the same time, it is important to establish whether responses to virtual stimuli mirror responses to depictions of a real conspecific. In the current study, we describe the development of a new virtual monkey head with realistic facial features for experiments with nonhuman primates, the "Primatar." As a first step toward validation, we assessed how monkeys respond to facial images of a prototype of this Primatar compared to images of real monkeys (RMs), and an unrealistic model. We also compared gaze responses between original images and scrambled as well as obfuscated versions of these images. We measured looking time to images in six freely moving long-tailed macaques (Macaca fascicularis) and gaze exploration behavior in three rhesus macaques (Macaca mulatta). Both groups showed more signs of overt attention to original images than scrambled or obfuscated images. In addition, we found no evidence for an uncanny valley effect; since for both groups, looking times did not differ between real, realistic, or unrealistic images. These results provide important data for further development of our Primatar for use in social cognition studies and more generally for cognitive research with virtual stimuli in nonhuman primates. Future research on the absence of an uncanny valley effect in macaques is needed, to elucidate the roots of this mechanism in humans.

Future Directions for Personality Research: Contributing New Insights to the Understanding of Animal Behavior.

As part of the European Conference on Behavioral Biology 2018, we organized a symposium entitled, "Animal personality: providing new insights into behavior?" The aims of this symposium were to address current research in the personality field, spanning both behavioral ecology and psychology, to highlight the future directions for this research, and to consider whether differential approaches to studying behavior contribute something new to the understanding of animal behavior. In this paper, we discuss the study of endocrinology and ontogeny in understanding how behavioral variation is generated and maintained, despite selection pressures assumed to reduce this variation. We consider the potential mechanisms that could link certain traits to fitness outcomes through longevity and cognition. We also address the role of individual differences in stress coping, mortality, and health risk, and how the study of these relationships could be applied to improve animal welfare. From the insights provided by these topics, we assert that studying individual differences through the lens of personality has provided new directions in behavioral research, and we encourage further research in these directions, across this interdisciplinary field.

A comparison of personality in the common and Bolivian squirrel monkey (Saimiri sciureus and Saimiri boliviensis).

Personality has been studied in all of the great apes, many Old World monkey species, but only a handful of New World monkey species. Because understanding the personalities of New World monkeys is crucial to understanding personality evolution in primates, we used the Hominoid Personality Questionnaire to assess personality in 55 common squirrel monkeys (Saimiri sciureus) and 40 Bolivian squirrel monkeys (Saimiri boliviensis). We found 4 personality components in each species, and labeled them Openness, Neuroticism, Assertiveness, and Agreeableness. We then, in a genus-level analysis, found 5 components, which we labeled Neuroticism, Openness, Assertiveness, Agreeableness, and Decisiveness. Comparisons of the genus- and species-level structures revealed that common squirrel monkeys had a personality structure that more closely resembled the genus-level structure than did Bolivian squirrel monkeys. We then compared the personality structures of common and Bolivian squirrel monkeys with that of brown capuchin monkeys, Sapajus apella. The personality structure of Bolivian squirrel monkeys more closely resembled that of brown capuchins. These findings suggest that the Bolivian squirrel monkey personality structure is ancestral and that Assertiveness and Openness are ancestral to both the Saimiri genus and brown capuchins; Agreeableness and Neuroticism seem to be derived in Saimiri. We discuss these findings in relation to differences in the social structures and ecologies of these species. (PsycINFO Database Record

Contradiction and Complacency Shape Attitudes towards the Toll of Roads on Wildlife.

Most people in the world now live in cities. Urbanisation simultaneously isolates people from nature and contributes to biodiversity decline. As cities expand, suburban development and the road infrastructure to support them widens their impact on wildlife. Even so, urban communities, especially those on the peri-urban fringe, endeavour to support biodiversity through wildlife friendly gardens, green spaces and corridors, and conservation estates. On one hand, many who live on city fringes do so because they enjoy proximity to nature, however, the ever increasing intrusion of roads leads to conflict with wildlife. Trauma (usually fatal) to wildlife and (usually emotional and financial) to people ensues. Exposure to this trauma, therefore, should inform attitudes towards wildlife vehicle collisions (WVC) and be linked to willingness to reduce risk of further WVC. While there is good anecdotal evidence for this response, competing priorities and better understanding of the likelihood of human injury or fatalities, as opposed to wildlife fatalities, may confound this trend. In this paper we sought to explore this relationship with a quantitative study of driver behaviour and attitudes to WVC from a cohort of residents and visitors who drive through a peri-urban reserve (Royal National Park) on the outskirts of Sydney, Australia. We distributed a self-reporting questionnaire and received responses from 105 local residents and 51 visitors to small townships accessed by roads through the national park. We sought the respondents' exposure to WVC, their evasive actions in an impending WVC, their attitudes to wildlife fatalities, their strategies to reduce the risk of WVC, and their willingness to adopt new ameliorative measures. The results were partitioned by driver demographics and residency. Residents were generally well informed about mitigation strategies but exposure led to a decrease in viewing WVC as very serious. In addition, despite most respondents stating they routinely drive slower when collision risk is high (at dusk and dawn), our assessment of driving trends via traffic speeds suggested this sentiment was not generally adhered to. Thus we unveil some of the complexities in tackling driver's willingness to act on reducing risk of WVC, particularly when risk of human trauma is low.

Using photographs to study animal social cognition and behaviour: Do capuchins' responses to photos reflect reality?

Behavioural responses to photos are often used to infer what animals understand about their social environment, but are rarely validated against the same stimuli in real life. If subjects' responses to photos do not reflect responses to the same live stimuli, it is difficult to conclude what happens in reality based on photo responses alone. We compared capuchins' responses to photos versus live stimuli in an identical scenario within research cubicles. Subjects had the opportunity to approach food placed in front of an alpha group member and, in a separate condition, photos depicting the same individual. Subjects' latencies to approach food when placed in front of the real alpha negatively correlated with time subjects spent in close proximity to the alpha in their main enclosure. We therefore predicted subjects' latencies to approach food in the presence of photos would positively correlate with their latencies to approach food in the presence of the real alpha inside the cubicles, but negatively correlate with time they spent in proximity to the alpha in their enclosure. Neither prediction was supported. While not necessarily surprising, we explain why these results should be an important reminder that care is needed when interpreting results from photo studies.

Comparing hyperbolic, delay-amount sensitivity and present-bias models of delay discounting.

Delay discounting is a widely studied phenomenon due to its ubiquity in psychopathological disorders. Several methods are well established to quantify the extent to which a delayed commodity is devalued as a function of the delay to its receipt. The most frequently used method is to fit a hyperbolic function and use an index of the gradient of the function, k, or to calculate the area under the discounting curve. The manuscript examines the behavior of these quantification indices for three different datasets, as well as provides information about potential limitations in their use. The primary limitation examined is the lack of mechanistic specificity provided by either method. Alternative formulations that are thought to provide some mechanistic information are examined for the three separate datasets: two variants of a hyperboloid model (Rachlin, 1989, Judgment, decision and choice. New York: W.H. Freeman) and the quasi-hyperbolic model (Laibson, 1997, Q. J. Econ., 112, 443-477). Examination of the parameters of each formulation suggests that the parameters derived from the quasi-hyperbolic model allows groups and conditions within the three datasets to be reliably distinguished more readily than the hyperboloid models. However, use of the quasi-hyperbolic model is complex and its limitations might offset its ability to discriminate within the datasets. "This article is part of a Special Issue entitled: SQAB 2014".

Characterizing heterogeneity in children with and without ADHD based on reward system connectivity.

One potential obstacle limiting our ability to clarify ADHD etiology is the heterogeneity within the disorder, as well as in typical samples. In this study, we utilized a community detection approach on 106 children with and without ADHD (aged 7-12 years), in order to identify potential subgroups of participants based on the connectivity of the reward system. Children with ADHD were compared to typically developing children within each identified community, aiming to find the community-specific ADHD characteristics. Furthermore, to assess how the organization in subgroups relates to behavior, we evaluated delay-discounting gradient and impulsivity-related temperament traits within each community. We found that discrete subgroups were identified that characterized distinct connectivity profiles in the reward system. Importantly, which connections were atypical in ADHD relative to the control children were specific to the community membership. Our findings showed that children with ADHD and typically developing children could be classified into distinct subgroups according to brain functional connectivity. Results also suggested that the differentiation in "functional" subgroups is related to specific behavioral characteristics, in this case impulsivity. Thus, combining neuroimaging data and community detection might be a valuable approach to elucidate heterogeneity in ADHD etiology and examine ADHD neurobiology.