Boosting arousal and cognitive performance through alternating posture: Insights from a multi-method laboratory study.

This study investigated the role of arousal and effort costs in the cognitive benefits of alternating between sitting and standing postures using a sit-stand desk, while measuring executive functions, self-reports, physiology, and neural activity in a 2-h laboratory session aimed to induce mental fatigue. Two sessions were conducted with a one-week gap, during which participants alternated between sitting and standing postures each 20-min block in one session and remained seated in the other. In each block, inhibition, switching, and updating were assessed. We examined effects of time-on-task, acute (local) effects of standing versus sitting posture, and cumulative (global) effects of a standing posture that generalize to the subsequent block in which participants sit. Results (N = 43) confirmed that time-on-task increased mental fatigue and decreased arousal. Standing (versus sitting) led to acute increases in arousal levels, including self-reports, alpha oscillations, and cardiac responses. Standing also decreased physiological and perceived effort costs. Standing enhanced processing speed in the flanker task, attributable to shortened nondecision time and speeded evidence accumulation processes. No significant effects were observed on higher-level executive functions. Alternating postures also increased heart rate variability cumulatively over time. Exploratory mediation analyses indicated that the positive impact of acute posture on enhanced drift rate was mediated by self-reported arousal, whereas decreased nondecision time was mediated by reductions in alpha power. In conclusion, alternating between sitting and standing postures can enhance arousal, decrease effort costs, and improve specific cognitive and physiological outcomes.

Female rats are less prone to clinical heart failure than male rats in a juvenile rat model of right ventricular pressure load.

Sex is increasingly emerging as determinant of right ventricular (RV) adaptation to abnormal loading conditions. It is unknown, however, whether sex-related differences already occur in childhood. Therefore, this study aimed to assess sex differences in a juvenile model of early RV pressure load by pulmonary artery banding (PAB) during transition from pre to postpuberty. Rat pups (n = 57, 3 wk old, 30-45 g) were subjected to PAB or sham surgery. Animals were euthanized either before or after puberty (4 and 8 wk postsurgery, respectively). Male PAB rats demonstrated failure to thrive already after 4 wk, whereas females did not. After 8 wk, female PAB rats showed less clinical symptoms of RV failure than male PAB rats. RV pressure-volume analysis demonstrated increased end-systolic elastance after 4 wk in females only, and a trend toward preserved end-diastolic elastance in female PAB rats compared with males (P = 0.055). Histology showed significantly less RV myocardial fibrosis in female compared with male PAB rats 8 wk after surgery. Myosin heavy chain 7-to-6 ratio switch and calcineurin signaling were less pronounced in female PAB rats compared with males. In this juvenile rat model of RV pressure load, female rats appeared to be less prone to clinical heart failure compared with males. This was driven by increased RV contractility before puberty, and better preservation of diastolic function with less RV myocardial fibrosis after puberty. These findings show that RV adaptation to increased loading differs between sexes already before the introduction of pubertal hormones.NEW & NOTEWORTHY In this study, we describe sex differences in our unique weanling rat model of increased RV pressure load by pulmonary artery banding. We are the first to assess temporal sex-related differences in RV adaptation during pubertal development. Female rats show superior RV function and less diastolic dysfunction and fibrosis compared with male rats. These differences are already present before puberty, indicating that the differences in RV adaptation are not only determined by sex hormones.

Multicenter Preclinical Validation of BET Inhibition for the Treatment of Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a degenerative arteriopathy that leads to right ventricular (RV) failure. BRD4 (bromodomain-containing protein 4), a member of the BET (bromodomain and extra-terminal motif) family, has been identified as a critical epigenetic driver for cardiovascular diseases.Objectives: To explore the therapeutic potential in PAH of RVX208, a clinically available BET inhibitor.Methods: Microvascular endothelial cells, smooth muscle cells isolated from distal pulmonary arteries of patients with PAH, rats with Sugen5416 + hypoxia- or monocrotaline + shunt-induced PAH, and rats with RV pressure overload induced by pulmonary artery banding were treated with RVX208 in three independent laboratories.Measurements and Main Results: BRD4 is upregulated in the remodeled pulmonary vasculature of patients with PAH, where it regulates FoxM1 and PLK1, proteins implicated in the DNA damage response. RVX208 normalized the hyperproliferative, apoptosis-resistant, and inflammatory phenotype of microvascular endothelial cells and smooth muscle cells isolated from patients with PAH. Oral treatment with RVX208 reversed vascular remodeling and improved pulmonary hemodynamics in two independent trials in Sugen5416 + hypoxia-PAH and in monocrotaline + shunt-PAH. RVX208 could be combined safely with contemporary PAH standard of care. RVX208 treatment also supported the pressure-loaded RV in pulmonary artery banding rats.Conclusions: RVX208, a clinically available BET inhibitor, modulates proproliferative, prosurvival, and proinflammatory pathways, potentially through interactions with FoxM1 and PLK1. This reversed the PAH phenotype in isolated PAH microvascular endothelial cells and smooth muscle cells in vitro, and in diverse PAH rat models. RVX208 also supported the pressure-loaded RV in vivo. Together, these data support the establishment of a clinical trial with RVX208 in patients with PAH.

A good beginning: study protocol for a group-randomized trial to investigate the effects of sit-to-stand desks on academic performance and sedentary time in primary education.

BACKGROUND: Sedentary behavior is associated with health risks and academic under-achievement in children. Still, children spend a large part of their waking hours sitting at a desk at school. Recent short-term studies demonstrated the potential of sit-to-stand desks to reduce sitting time in primary education. The program of "A Good Beginning" was conceived to assess the long-term effects of sit-to-stand desks on sitting time in primary education, and to examine how sit-to-stand desks versus regular desks relate to academic performance, and measures of executive functioning, health and wellbeing. The present paper describes the design of this group-randomized trial, which started in 2017 and will be completed in 2019. METHODS: Children of two grade-three groups (age 8-9) following regular primary education in Leiden, The Netherlands, were recruited. A coin toss determined which group is the experimental group; the other group is the control group. All children in the experimental group received sit-to-stand desks. They are invited and motivated to reduce sedentary time at school, however, it is their own choice to sit or stand. Children in the control group use regular desks. Otherwise, both groups receive regular treatment. Outcomes are assessed at baseline (T0) and at five follow-up sessions (T1-T5) alternately in winter and summer seasons over three academic years. Primary outcome measures are academic performance, and the proportion of sitting time at school, measured with a 3D accelerometer. Secondary outcome measures are a number of measures related to executive functioning (e.g., N-back task for working memory), health (e.g., height and weight for BMI), and wellbeing (e.g., KIDSCREEN-52 for Quality of Life). DISCUSSION: A Good Beginning is a two-and-a-half-year research program, which aims to provide a better understanding of the long-term effects of sit-to-stand desks on sedentary time at school and the relation between sitting time reduction and academic performance, executive functioning, health and wellbeing. The findings may serve as useful information for policy making and practical decision making for school and classroom environments. TRIAL REGISTRATION: The program of "A Good Beginning" is registered at the Netherlands Trial Register (NTR, https://www.trialregister.nl), number NL6166, registration date 24 November 2016.

EEG Theta/Beta Ratio Neurofeedback Training in Healthy Females.

A growing number of studies suggest that EEG theta/beta ratio (TBR) is inversely related to executive cognitive control. Neurofeedback training aimed at reducing TBR (TBR NFT) might provide a tool to study causality in this relation and might enhance human performance. To investigate whether TBR NFT reduces TBR in healthy participants. Twelve healthy female participants were assigned (single blind) to one of three groups. Groups differed on baseline durations and one group received only sham NFT. TBR NFT consisted of eight or fourteen 25-min sessions. No evidence was found that TBR NFT had any effect on TBR. The current TBR NFT protocol is possibly ineffective. This is in line with a previous study with a different protocol.

A novel method optimizing the normalization of cardiac parameters in small animal models: the importance of dimensional indexing.

For indexing cardiac measures in small animal models, tibia length (TL) is a recommended surrogate for body weight (BW) that aims to avoid biases because of disease-induced BW changes. However, we question if indexing by TL is mathematically correct. This study aimed to investigate the relation between TL and BW, heart weight, ventricular weights, and left ventricular diameter to optimize the current common practice of indexing cardiac parameters in small animal models. In 29 healthy Wistar rats (age 5-34 wk) and 116 healthy Black 6 mice (age 3-17 wk), BW appeared to scale nonlinearly to TL1 but linearly to TL3. Formulas for indexing cardiac weights were derived. To illustrate the effects of indexing, cardiac weights between the 50% with highest BW and the 50% with lowest BW were compared. The nonindexed cardiac weights differed significantly between groups, as could be expected (P < 0.001). However, after indexing by TL1, indexed cardiac weights remained significantly different between groups (P < 0.001). With the derived formulas for indexing, indexed cardiac weights were similar between groups. In healthy rats and mice, BW and heart weights scale linearly to TL3. This indicates that not TL1 but TL3 is the optimal surrogate for BW. New formulas for indexing heart weight and isolated ventricular weights are provided, and we propose a concept in which cardiac parameters should not all be indexed to the same measure but one-dimensional measures to BW1/3 or TL1, two-dimensional measures to BW2/3 or TL2, and three-dimensional measures to BW or TL3. NEW & NOTEWORTHY In healthy rats and mice, body weight (BW) scales linearly to tibia length (TL) to the power of three (TL3). This indicates that for indexing cardiac parameters, not TL1 but TL3 is the optimal surrogate for BW. New formulas for indexing heart weight and isolated ventricular weights are provided, and we propose a concept of dimensionally consistent indexing. This concept is proposed to be widely applied in small animal experiments.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study.

BACKGROUND: Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. METHODS: We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. FINDINGS: Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. INTERPRETATION: Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. FUNDING: National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Game-based training of flexibility and attention improves task-switch performance: near and far transfer of cognitive training in an EEG study.

There is a demand for ways to enhance cognitive flexibility, as it can be a limiting factor for performance in daily life. Video game training has been linked to advantages in cognitive functioning, raising the question if training with video games can promote cognitive flexibility. In the current study, we investigated if game-based computerized cognitive training (GCCT) could enhance cognitive flexibility in a healthy young adult sample (N = 72), as measured by task-switch performance. Three GCCT schedules were contrasted, which targeted: (1) cognitive flexibility and task switching, (2) attention and working memory, or (3) an active control involving basic math games, in twenty 45-min sessions across 4-6 weeks. Performance on an alternating-runs task-switch paradigm during pretest and posttest sessions indicated greater overall reaction time improvements after both flexibility and attention training as compared to control, although not related to local switch cost. Flexibility training enhanced performance in the presence of distractor-related interference. In contrast, attention training was beneficial when low task difficulty undermined sustained selective attention. Furthermore, flexibility training improved response selection as indicated by a larger N2 amplitude after training as compared to control, and more efficient conflict monitoring as indicated by reduced Nc/CRN and larger Pe amplitude after training. These results provide tentative support for the efficacy of GCCT and suggest that an ideal training might include both task switching and attention components, with maximal task diversity both within and between training games.

Hedonic Hotspots Regulate Cingulate-driven Adaptation to Cognitive Demands.

Positive hedonic states are known to attenuate the impact of demanding events on our body and brain, supporting adaptive behavior in response to changes in the environment. We used functional magnetic resonance imaging to examine the neural mechanism of this hedonic regulation. The effect of hedonic state (as induced by funny vs. neutral cartoons) on flexible behavioral and neural adaptation to cognitive demands was assessed in a flanker task in female volunteers. Behavioral results showed that humor reduced the compensatory adjustments to cognitive demands, as observed in sequential adaptations. This modulation was also reflected in midcingulate cortex (MCC; also known as the dorsal anterior cingulate cortex, ACC) activation. Furthermore, hedonic context increased activation in ventral striatum (VS) and ventral pallidum (VP). These hedonic hotspots attenuated the medial prefrontal cortex response to the cognitive demands in the ACC (also known as the rostral ACC). Activity in the ACC proved predictive of subsequent behavioral adaptation. Moreover, psychophysiological interaction analyses revealed that the MCC and the ACC were functionally connected with VS and VP, respectively. These observations reveal how MCC-VS and VP-ACC interactions are involved in the detection and hedonic modulation of behavioral adaptations to cognitive demands, which supports behavioral flexibility.

Increasing efficiency of surgical training: effects of spacing practice on skill acquisition and retention in laparoscopy training.

OBJECTIVES: The goal of this study was to investigate the effects of spaced versus massed practice on skill acquisition and retention in the context of laparoscopic motor skill training. BACKGROUND: Reaching proficiency in performing laparoscopic surgery involves extensive training to acquire the required motor skills. Conventionally, training of such skills occurs during a full day training event utilizing surgical simulators that train specific motor skills pertinent to laparoscopic surgery. An important variable to consider is the optimal schedule for laparoscopic motor training. METHODS: In this study, two groups of trainees without prior experience were trained on a variety of physical box-trainer tasks on different time-schedules. One group received three 75-min training sessions on a single day (massed condition) and the other received one 75-min training session per week for three consecutive weeks (spaced condition). Short- and long-term retention were assessed 2 weeks and 1 year after the completion of training. RESULTS: Outcome measures indicated better performance at the end of training, at a 2-week delayed retention session and at a 1-year retention session for the group that received training on a spaced schedule. This spacing effect was most pronounced for the more difficult laparoscopic training tasks such as intra-corporeal suturing. On average, 21 % of participants in the massed group and 65 % in the spaced group reached proficiency by the end of training. CONCLUSIONS: Spacing practice of laparoscopic motor skill training will facilitate skill acquisition, short-term and long-term retention, and thus, a more efficient learning process for trainees. Though more challenging in terms of logistics, training courses in medical centers should distribute practice sessions over longer time intervals.

[Mindfulness-Based Cognitive Therapy (MBCT) and the 'Third Wave' of Cognitive-Bahavioral Therapies (CBT)]. / Terapia Cognitiva basada en Atención Plena (mindfulness) y la 'tercera ola' en Terapias Cognitivo-Conductuales.

The paper presents the reasons that led to the incorporation of mindfulness as part of a cognitive therapy approach to the prevention of relapse of recurrent depressive disorders. It describes the context in which models focused on the contents of cognition gave way to models focused on cognitive processes. We highlight the problems encountered by the standard cognitive model when trying to account for the cognitive vulnerability of individuals who, having experienced a depressive episode, are in remission. We briefly describe the theoretical foundations of Mindfulness-Based Cognitive Therapy and its therapeutic approach.

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

BACKGROUND: Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. METHODS: We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. FINDINGS: Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). INTERPRETATION: Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease. FUNDING: National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City.

A Fourier-domain algorithm for total-variation regularized phase retrieval in differential X-ray phase contrast imaging.

Phase retrieval in differential X-ray phase contrast imaging involves a one dimensional integration step. In the presence of noise, standard integration methods result in image blurring and streak artifacts. This work proposes a regularized integration method which takes the availability of two dimensional data as well as the integration-specific frequency-dependent noise amplification into account. In more detail, a Fourier-domain algorithm is developed comprising a frequency-dependent minimization of the total variation orthogonal to the direction of integration. For both simulated and experimental data, the novel method yielded strong artefact reduction without increased blurring superior to the results obtained by standard integration methods or regularization techniques in the image domain.

Optimal training design for procedural motor skills: a review and application to laparoscopic surgery.

This literature review covers the choices to consider in training complex procedural, perceptual and motor skills. In particular, we focus on laparoscopic surgery. An overview is provided of important training factors modulating the acquisition, durability, transfer, and efficiency of trained skills. We summarize empirical studies and their theoretical background on the topic of training complex cognitive and motor skills that are pertinent to proficiency in laparoscopic surgery. The overview pertains to surgical simulation training for laparoscopy, but also to training in other demanding procedural and dexterous tasks, such as aviation, managing complex systems and sports. Evidence-based recommendations are provided for facilitating efficiency in laparoscopic motor skill training such as session spacing, adaptive training, task variability, part-task training, mental imagery and deliberate practice.

Vagus nerve stimulation in pediatric patients with drug-resistant epilepsy: a step-by-step video.

Vagus nerve stimulation (VNS) is a neuromodulatory treatment involving chronic intermittent electrical stimulation of the left vagus nerve, administered through a programmable pulse generator implanted subcutaneously in the chest. This generator connects to a bipolar lead, with electrodes wrapped around the vagus nerve in the neck. Primarily used as an adjunct therapy for patients with refractory epilepsy who cannot undergo or have not benefitted from resective surgery, VNS is generally well tolerated with few severe side effects. Herein is presented an educational surgical video providing a detailed, step-by-step technical description of VNS implantation. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID244.

Surgical Anatomy and Technique of Peri-Insular Hemispherotomy in Pediatric Epilepsy.

BACKGROUND AND OBJECTIVES: Hemispherotomy is a highly complex procedure that demands a steep learning curve. An incomplete brain disconnection often results in failure of seizure control. The purpose of this article was to present a step-by-step guide to the surgical anatomy of this procedure. It is composed of a 7-stage approach, enhancing access to and improving visualization of deep structures. METHODS: A retrospective analysis of 39 pediatric patients with refractory epilepsy who underwent this technique was conducted. Engel scores were assessed 1 year postsurgery. Cadaveric dissections were performed to illustrate the procedure. RESULTS: Between 2015 and 2022, 39 patients were surgically treated using the peri-insular technique. The technique involved 7 stages: patient positioning, operative approach, opercular resection, transventricular callosotomy, fronto-orbital disconnection, anterior temporal disconnection, and posterior temporal disconnection. Most of the patients (92.30%) were seizure-free (Engel class I) at 1 year postoperative, 5.13% were nearly seizure-free (Engel II), and 2.56% showed significant improvement (Engel III). Complications occurred in 8% of cases, including 1 infection, 2 cases of aseptic meningitis, and 1 non-shunt-requiring acute hydrocephalus. CONCLUSION: The peri-insular hemispherotomy technique offers excellent seizure control with a low complication rate. Our visual documentation of surgical anatomy, complemented by detailed descriptions of surgical nuances, significantly contributes to a comprehensive understanding of this technique.

Changes in neural connectivity underlie decision threshold modulation for reward maximization.

Using neuroimaging in combination with computational modeling, this study shows that decision threshold modulation for reward maximization is accompanied by a change in effective connectivity within corticostriatal and cerebellar-striatal brain systems. Research on perceptual decision making suggests that people make decisions by accumulating sensory evidence until a decision threshold is crossed. This threshold can be adjusted to changing circumstances, to maximize rewards. Decision making thus requires effectively managing the amount of accumulated evidence versus the amount of available time. Importantly, the neural substrate of this decision threshold modulation is unknown. Participants performed a perceptual decision-making task in blocks with identical duration but different reward schedules. Behavioral and modeling results indicate that human subjects modulated their decision threshold to maximize net reward. Neuroimaging results indicate that decision threshold modulation was achieved by adjusting effective connectivity within corticostriatal and cerebellar-striatal brain systems, the former being responsible for processing of accumulated sensory evidence and the latter being responsible for automatic, subsecond temporal processing. Participants who adjusted their threshold to a greater extent (and gained more net reward) also showed a greater modulation of effective connectivity. These results reveal a neural mechanism that underlies decision makers' abilities to adjust to changing circumstances to maximize reward.

Happy but still focused: failures to find evidence for a mood-induced widening of visual attention.

In models of affect and cognition, it is held that positive affect broadens the scope of attention. Consistent with this claim, previous research has indeed suggested that positive affect is associated with impaired selective attention as evidenced by increased interference of spatially distant distractors. However, several recent findings cast doubt on the reliability of this observation. In the present study, we examined whether selective attention in a visual flanker task is influenced by positive mood induction. Across three experiments, positive affect consistently failed to exert any impact on selective attention. The implications of this null-finding for theoretical models of affect and cognition are discussed.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. Methodology: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Results: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Conclusions and Implications: Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.