Active neural coordination of motor behaviors with internal states.

The brain continuously coordinates skeletomuscular movements with internal physiological states like arousal, but how is this coordination achieved? One possibility is that the brain simply reacts to changes in external and/or internal signals. Another possibility is that it is actively coordinating both external and internal activities. We used functional ultrasound imaging to capture a large medial section of the brain, including multiple cortical and subcortical areas, in marmoset monkeys while monitoring their spontaneous movements and cardiac activity. By analyzing the causal ordering of these different time series, we found that information flowing from the brain to movements and heart-rate fluctuations were significantly greater than in the opposite direction. The brain areas involved in this external versus internal coordination were spatially distinct, but also extensively interconnected. Temporally, the brain alternated between network states for this regulation. These findings suggest that the brain's dynamics actively and efficiently coordinate motor behavior with internal physiology.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

Internal states and extrinsic factors both determine monkey vocal production.

A key question for understanding speech evolution is whether or not the vocalizations of our closest living relatives-nonhuman primates-represent the precursors to speech. Some believe that primate vocalizations are not volitional but are instead inextricably linked to internal states like arousal and thus bear little resemblance to human speech. Others disagree and believe that since many primates can use their vocalizations strategically, this demonstrates a degree of voluntary vocal control. In the current study, we present a behavioral paradigm that reliably elicits different types of affiliative vocalizations from marmoset monkeys while measuring their heart rate fluctuations using noninvasive electromyography. By modulating both the physical distance between marmosets and the sensory information available to them, we find that arousal levels are linked, but not inextricably, to vocal production. Different arousal levels are, generally, associated with changes in vocal acoustics and the drive to produce different call types. However, in contexts where marmosets are interacting, the production of these different call types is also affected by extrinsic factors such as the timing of a conspecific's vocalization. These findings suggest that variability in vocal output as a function of context might reflect trade-offs between the drive to perpetuate vocal contact and conserving energy.

Age and Age Discordance Associations with Condomless Sex Among Men Who Have Sex with Men.

We explored the effect of older partner's age and age difference between partners on condomless sex among men who have sex with men (MSM). We analyzed dyads (n = 1720) from participants (n = 969) in the Sexual Acquisition Transmission of HIV Cooperative Agreement Program. We used modified Poisson regression to model the probability of a sexual encounter's being condomless as a function of older partner's age and age difference between partners adjusting for HIV status, substance use, race/ethnicity, and partner type. We found an interaction between older partner's age and age difference (p < 0.05). Condomless sex decreased with increasing age of the older partner when the age difference was 5-9 years (p = 0.004) or ≥10 years (p = 0.04), but not when <5 years. Condomless sex was less likely among older MSM when there was ≥5 years age difference between partners than <5 years difference. Both age and age discordance affect the likelihood of a sexual encounter between MSM being condomless.

Social networks and alcohol use among older adults: a comparison with middle-aged adults.

OBJECTIVES: This study compared the association between social networks and alcohol consumption among middle-aged (MA) and older adults (OA) to better understand the nature of the relationship between those two factors among OA and MA. METHOD: We examined Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Current drinkers aged over 50 were subdivided into two age groups: MA (50-64, n = 5214) and OA (65 and older, n = 3070). Each age group was stratified into drinking levels (low-risk vs. at-risk) based on alcohol consumption. The size and diversity of social networks were measured. Logistic regression models were used to examine age differences in the association between the social networks (size and diversity) and the probability of at-risk drinking among two age groups. RESULTS: A significant association between the social networks diversity and lower odds of at-risk drinking was found among MA and OA. However, the relationship between the diversity of social networks and the likelihood of at-risk drinking was weaker for OA than for MA. The association between social networks size and at-risk drinking was not significant among MA and OA. CONCLUSION: The current study suggests that the association between social networks diversity and alcohol use among OA differs from the association among MA, and few social networks were associated with alcohol use among OA. In the future, research should consider an in-depth exploration of the nature of social networks and alcohol consumption by using longitudinal designs and advanced methods of exploring drinking networks.

Psychiatric correlates of alcohol and tobacco use disorders in U.S. adults aged 65 years and older: results from the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions.

OBJECTIVE: To examine associations of alcohol and tobacco use disorders and psychiatric conditions among older U.S. adults. METHODS: Sample was individuals aged at least 65 years (N = 8,205) who participated in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Measurements included lifetime and past 12-month Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol use disorders (AUDs), tobacco use disorders (TUDs), and psychiatric conditions. RESULTS: Among older adults, prevalence of lifetime and past 12-month AUDs were 16.1% and 1.5% and lifetime and past 12-month TUDs were 8.7% and 4.0%, respectively. Lifetime TUD was associated with increased odds of both lifetime (odds ratio [OR]: 4.17; 95% confidence interval [CI]: 3.30-5.26) and past 12-month (OR: 2.52; 95% CI: 1.50-4.24) AUDs, and lifetime AUD was associated with increased odds of both lifetime (OR: 4.13; 95% CI: 3.28-5.210 and past 12-month (OR: 3.51; 95% CI: 2.47-4.96) TUDs. Any lifetime mood, anxiety, or personality disorder among older adults was associated with increased odds of lifetime AUD and TUD, any lifetime mood disorder was associated with increased odds of past 12-month AUD and TUD, and any personality disorder was associated with past 12-month TUD. CONCLUSION: There is a strong association between AUD and TUD among older U.S. adults as well as associations between AUD and TUD with mood, anxiety, and personality disorders. Understanding the psychiatric conditions associated with AUDs and TUDs, especially past 12-month use disorders involving alcohol or tobacco, will enable healthcare providers to target screening and be more aware of symptoms and signs of potential AUDs and TUDs among those at higher risk.

Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.

Crows "count" the number of self-generated vocalizations.

Producing a specific number of vocalizations with purpose requires a sophisticated combination of numerical abilities and vocal control. Whether this capacity exists in animals other than humans is yet unknown. We show that crows can flexibly produce variable numbers of one to four vocalizations in response to arbitrary cues associated with numerical values. The acoustic features of the first vocalization of a sequence were predictive of the total number of vocalizations, indicating a planning process. Moreover, the acoustic features of vocal units predicted their order in the sequence and could be used to read out counting errors during vocal production.

Proprotein convertase subtisilin/kexin 9 levels decline with hepatitis C virus therapy in people with HIV/hepatitis C virus and correlate with inflammation.

BACKGROUND: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. DESIGN: A prospective, observational cohort study. METHODS: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. RESULTS: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P  = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml ( P  = 0.003) and -55.6 ng/ml ( P  = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r  = 0.64, P  = 0.002; r  = 0.58, P  = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks. CONCLUSION: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.

Efficient and robust identification of cortical targets in concurrent TMS-fMRI experiments.

Transcranial magnetic stimulation (TMS) can be delivered during fMRI scans to evoke BOLD responses in distributed brain networks. While concurrent TMS-fMRI offers a potentially powerful tool for non-invasively investigating functional human neuroanatomy, the technique is currently limited by the lack of methods to rapidly and precisely localize targeted brain regions - a reliable procedure is necessary for validly relating stimulation targets to BOLD activation patterns, especially for cortical targets outside of motor and visual regions. Here we describe a convenient and practical method for visualizing coil position (in the scanner) and identifying the cortical location of TMS targets without requiring any calibration or any particular coil-mounting device. We quantified the precision and reliability of the target position estimates by testing the marker processing procedure on data from 9 scan sessions: Rigorous testing of the localization procedure revealed minimal variability in coil and target position estimates. We validated the marker processing procedure in concurrent TMS-fMRI experiments characterizing motor network connectivity. Together, these results indicate that our efficient method accurately and reliably identifies TMS targets in the MR scanner, which can be useful during scan sessions for optimizing coil placement and also for post-scan outlier identification. Notably, this method can be used generally to identify the position and orientation of MR-compatible hardware placed near the head in the MR scanner.

Recursive sequence generation in crows.

Recursion, the process of embedding structures within similar structures, is often considered a foundation of symbolic competence and a uniquely human capability. To understand its evolution, we can study the recursive aptitudes of nonhuman animals. We adopted the behavioral protocol of a recent study demonstrating that humans and nonhuman primates grasp recursion. We presented sequences of bracket pair stimuli (e.g., [ ] and { }) to crows who were instructed to peck at training lists. They were then tested on their ability to transfer center-embedded structure to never-before-seen pairings of brackets. We reveal that crows have recursive capacities; they perform on par with children and even outperform macaques. The crows continued to produce recursive sequences after extending to longer and thus deeper embeddings. These results demonstrate that recursive capabilities are not limited to the primate genealogy and may have occurred separately from or before human symbolic competence in different animal taxa.

Alcohol, tobacco, and nonmedical drug use disorders in U.S. Adults aged 65 years and older: data from the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions.

OBJECTIVES: To examine the prevalence, sociodemographic, and health-related correlates of substance use disorders, including alcohol, tobacco, and nonmedical drug use among adults aged 65 years and older. DESIGN: The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a cross-sectional survey of a population-based sample. SETTING: The United States. PARTICIPANTS: Eight thousand two hundred five adults aged 65 years and older. MEASUREMENTS: Prevalence of lifetime and past 12-month Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, determined alcohol, tobacco, and nonmedical drug use disorders. RESULTS: Prevalence of any substance use disorder was 21.1% during the lifetime and 5.4% in the past 12 months. Lifetime and past 12-month alcohol use disorders were 16.1% and 1.5%; tobacco use disorders were 8.7% and 4.0%; and nonmedical drug use disorders were 0.6% and 0.2%, respectively. Younger age was associated with greater odds of any lifetime or past 12-month substance use disorders. Men and those who were divorced or separated had greater odds of both lifetime alcohol and tobacco use disorders. Very good or excellent self-rated health was associated with lower odds of lifetime and past 12-month tobacco use disorders. Younger age and being divorced or separated were associated with greater odds of lifetime nonmedical drug use disorder. CONCLUSIONS: More than one in five older adults ever had a substance use disorder, and more than 1 in 20 had a disorder in the past 12 months, primarily involving alcohol or tobacco. Older adults have increased comorbidities and use of medications, which can increase risks associated with substance use.

The content of substance abuse and mental health counseling reported by patients in a national survey.

This study examined counseling content reported by a national sample of persons receiving care for alcohol, drug or mental health (ADM) problems in a year. The sample included 2,722 individuals over 18 who reported past year mental health or substance abuse care or assessments in a nationally representative survey conducted in 2000-2001. Counseling domains approximating commonly practiced or evidence-based approaches for depression, anxiety, or substance abuse were assessed. Patient self-report may be one useful way of tracking whether components of standard therapies are implemented in practice.

Author Correction: Vocal state change through laryngeal development.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Modified Alcohol SBI for Use among Older Adults Living with HIV.

Older adults living with HIV may have health conditions that amplify the potentially negative health effects of alcohol use. We adapted the Comorbidity Alcohol Risk Evaluation Tool (CARET) screening tool for at-risk drinking to reflect HIV/AIDS and related conditions, medications, and behaviors. The adapted CARET-HIV along with a brief intervention was administered to 27 older men living with HIV. The CARET-HIV identified the same number of at-risk drinkers as the original CARET (n = 24) but identified more risk domains. Most participants welcomed receiving information about risks associated with their drinking, but some felt "embarrassed" or "guilty" discussing their drinking. This is particularly salient within the context of HIV discourse, which has historically assigned blame of HIV infection on personal choices. The SBI was generally acceptable to participants. The modified CARET can help providers integrate discussion of alcohol use into the context of HIV care for personalized feedback.

Trabecular Bone Score Declines During the Menopause Transition: The Study of Women's Health Across the Nation (SWAN).

CONTEXT: Rapid bone density loss starts during the menopause transition (MT). Whether other components of bone strength deteriorate before the final menstrual period (FMP) remains uncertain. OBJECTIVE: To discern whether trabecular bone score (TBS) declines during the MT. DESIGN: An 18-year longitudinal analysis from the Study of Women's Health Across Nation. SETTING: Community-based cohort. PARTICIPANTS: A total of 243 black, 164 Japanese, and 298 white, initially pre- or early perimenopausal women, who experienced their FMP. MAIN OUTCOME MEASURES: TBS, an indicator of bone strength. RESULTS: Multivariable mixed effects regressions fitted piecewise linear models to repeated measures of TBS as a function of time before or after the FMP; covariates were age at FMP, race/ethnicity, and body mass index. Prior to 1.5 years before the FMP, in the referent individual (a white woman with age at FMP of 52.2 years and body mass index of 28.0 kg/m2), TBS evidenced no change (slope 0.12% per year, P = 0.2991). TBS loss began 1.5 years before the FMP, declining by 1.16% annually (P < 0.0001). Starting 2 years after the FMP, annual rate of TBS loss lessened to 0.89% (P < 0.0001). In the 5 years before through the 5 years after the FMP, in the referent individual, total TBS decline was 6.3% (P < 0.0001), but black participants' total TBS loss was 4.90% (P = 0.0008, difference in black and white 10-year change). Results for Japanese did not differ from those of white women. CONCLUSIONS: The occurrence of an MT-related decline in TBS supports the thesis that this period is particularly damaging to skeletal integrity.

Light to moderate alcohol consumption and disability: variable benefits by health status.

In adults, light to moderate alcohol consumption is associated with lower risks for heart disease, diabetes, and mortality. This study examined whether light to moderate alcohol use is also associated with lower risk of incident physical disability over two 5-year periods in 4,276 noninstitutionalized adults in the United States, aged 50 years or older, by using data from 3 waves of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study surveys from 1982 to 1992. Light/moderate drinking (<15 drinks per week and <5 per drinking day or 4 per drinking day for women) was associated with reduced risk for incident disability or death over 5 years, compared with abstention (adjusted odds ratio = 0.77; P = 0.008). Among survivors, light/moderate drinking was associated with lower risk for incident disability, compared with abstention (adjusted odds ratio = 0.75; P = 0.009). In stratified analyses, disability risk decreased with light/moderate drinking in a dose-dependent fashion in men and women with good or better self-reported health but not in men or women with fair or worse self-reported health. Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor health.

Vocal state change through laryngeal development.

Across vertebrates, progressive changes in vocal behavior during postnatal development are typically attributed solely to developing neural circuits. How the changing body influences vocal development remains unknown. Here we show that state changes in the contact vocalizations of infant marmoset monkeys, which transition from noisy, low frequency cries to tonal, higher pitched vocalizations in adults, are caused partially by laryngeal development. Combining analyses of natural vocalizations, motorized excised larynx experiments, tensile material tests and high-speed imaging, we show that vocal state transition occurs via a sound source switch from vocal folds to apical vocal membranes, producing louder vocalizations with higher efficiency. We show with an empirically based model of descending motor control how neural circuits could interact with changing laryngeal dynamics, leading to adaptive vocal development. Our results emphasize the importance of embodied approaches to vocal development, where exploiting biomechanical consequences of changing material properties can simplify motor control, reducing the computational load on the developing brain.

Daily factors driving daily substance use and chronic pain among older adults with HIV: An exploratory study using ecological momentary assessment.

BACKGROUND: Adults 50 and older make up approximately 50% of persons living with HIV. Multiple co-morbidities are common among this group, including chronic pain and substance abuse, yet little is known about the daily factors that either enhance or inhibit these experiences or behaviors. This study explored daily drivers of substance use, pain, and relief from pain among older adults living with HIV utilizing ecological momentary assessment (EMA). METHOD: Participants (N = 55), ages 49-71, completed seven consecutive days of daily EMA online surveys prior to treatment initiation within a randomized controlled trial. Multilevel modeling tested predictors of pain, substance use, and relief from pain by examining within- and between-person relationships. RESULTS: Results revealed an associational, reciprocal relationship between daily worst pain and daily drinking, where greater worst pain ratings predicted heavier drinking and heavier drinking predicted greater daily and overall pain. Greater happiness and poorer quality of sleep predicted greater daily worst pain. Exercising and overall confidence to cope with pain without medication were associated with lower levels of daily worst pain. Finally, spending less time with a loved one over time and reporting any coping behavior were associated with relief from pain. CONCLUSION: Investigation of daily factors that drive pain and substance use behaviors among this unique population help inform which daily factors are most risky to their health and well-being. Alcohol use emerged as the only substance associated with both driving pain and responding to pain. Findings suggest key points for prevention and intervention.