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The brainstem’s lateral superior olive (LSO) is thought to be crucial for localizing high-frequency sounds by coding interaural sound level differences (ILD). Its neurons weigh contralateral inhibition against ipsilateral excitation, making their firing rate a function of the azimuthal position of a sound source. Since the very first in vivo recordings, LSO principal neurons have been reported to give sustained and temporally integrating ‘chopper’ responses to sustained sounds. Neurons with transient responses were observed but largely ignored and even considered a sign of pathology. Using the Mongolian gerbil as a model system, we have obtained the first in vivo patch clamp recordings from labeled LSO neurons and find that principal LSO neurons, the most numerous projection neurons of this nucleus, only respond at sound onset and show fast membrane features suggesting an importance for timing. These results provide a new framework to interpret previously puzzling features of this circuit.

Locomotion generates adventitious sounds which enable detection and localization of predators and prey. Such sounds contain brisk changes or transients in amplitude. We investigated the hypothesis that ill-understood temporal specializations in binaural circuits subserve lateralization of such sound transients, based on different time of arrival at the ears (interaural time differences, ITDs). We find that Lateral Superior Olive (LSO) neurons show exquisite ITD-sensitivity, reflecting extreme precision and reliability of excitatory and inhibitory postsynaptic potentials, in contrast to Medial Superior Olive neurons, traditionally viewed as the ultimate ITD-detectors. In vivo, inhibition blocks LSO excitation over an extremely short window, which, in vitro, required synaptically evoked inhibition. Light and electron microscopy revealed inhibitory synapses on the axon initial segment as the structural basis of this observation. These results reveal a neural vetoing mechanism with extreme temporal and spatial precision and establish the LSO as the primary nucleus for binaural processing of sound transients.

The current study examined the relationship between acute (past 30 day) and recent (past year but not past 30 day) serious psychological distress (SPD) and smoking during pregnancy among women in the United States overall, stratified by demographic characteristics, and described the change in the prevalence of prenatal smoking among women with and without SPD, from 2008 to 2014. Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons aged 12 and over. SPD and smoking in the past 30 days among pregnant women, aged 18 and older, were examined using logistic regression models. Heterogeneity in this association by demographic characteristics, trends over time, and level of cigarette consumption was also examined. Prenatal smoking was common. Almost 40% of pregnant women with acute SPD reported smoking, 23% of pregnant women with recent SPD smoked, and 11.7% of pregnant women without recent SPD smoked. No significant change was found in the prevalence of prenatal smoking from 2008 to 2014 in any of these groups. Robust relationships were found between acute (OR = 5.05 [3.64-6.99]) and recent SPD (OR = 2.37 [1.74-3.24]) and smoking; these findings remained after adjusting for demographics. SPD and smoking during pregnancy are strongly associated; this relationship is present across all sociodemographic groups and the prevalence of smoking in pregnancy has remained relatively unchanged over the past decade both in the presence and absence of SPD. SPD and smoking in pregnancy are robustly linked; the prevalence of smoking in pregnancy is extremely high in women with SPD. Screening women with mental health problems for prenatal smoking, as well as screening pregnant smokers for mental health problems, seems warranted and may assist more women in seeking and utilizing treatment options. Efforts to reduce the prevalence of smoking during pregnancy might specifically target women with SPD, where the potential for impact is substantial.

Objectives Those with any psychiatric diagnosis have substantially greater rates of smoking and are less likely to quit smoking than those with no diagnosis. Using nationally representative data, we sought to provide estimates of smoking and longitudinal cessation rates by specific psychiatric diagnoses and mental health service use. Design and participants Data were analysed from a two-wave cohort survey of a US nationally representative sample (non-institutionalised adults): the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001–2002, n=43 093; 2004–2005, n=34 653). Main outcome measures We examined smoking rates (lifetime, past year and past year heavy) and cross-sectional quit rates among those with any lifetime or past year psychiatric diagnosis (DSM-IV). Importantly, we examined longitudinal quit rates and conducted analyses by gender and age categories. Results Those with any current psychiatric diagnosis had 3.23 (95% CI 3.11 to 3.35) times greater odds of currently smoking than those with no diagnosis, and were 25% less likely to have quit by follow-up (95% CI 20% to 30%). Prevalence varied by specific diagnoses (32.4% to 66.7%) as did cessation rates (10.3% to 17.9%). Comorbid disorders were associated with higher proportions of heavy smoking. Treatment use was associated with greater prevalence of smoking and lower likelihood of cessation. Conclusions Those with psychiatric diagnoses remained much more likely to smoke and less likely to quit, with rates varying by specific diagnosis. Our findings highlight the need to improve our ability to address smoking and psychiatric comorbidity both within and outside of healthcare settings. Such advancements will be vital to reducing mental illness-related disparities in smoking and continuing to decrease tobacco use globally.

Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide-frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized in vivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from across-frequency coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of hot spot frequencies. A simple biophysical octopus cell model excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with the activation sequence of clustered excitatory inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.

Background Recent data suggest that excessive alcohol use is increasing among women and older adults. Such trends are concerning, as women are more vulnerable to alcohol-related health consequences, and such health problems may be exacerbated with age. Furthermore, there are sex-specific factors that may influence alcohol consumption among women, including the hormonal changes associated with the menopausal transition and negative affect. The present study sought to investigate transitions in excessive drinking among women across the menopausal transition and included exploration of sex hormones (estradiol; testosterone) and depression. Methods The present study utilized publicly available data from the Study of Women Across the Nation (SWAN) and included 3302 women (42–52 years old at baseline), who completed 10 years of annual assessments. National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria were used as guidance when defining excessive drinking within the present dataset. At year 1, 170 women were identified as drinking excessively. Random-effect logistic regressions were used to examine transitions in excessive drinking. Results Women identified as excessive drinkers were more likely to transition to non-excessive drinking across all menopausal transition stages ( ORs range = 3.71–5.11), while women were more likely to transition from non-excessive to excessive drinking during the early peri- and postmenopausal stages ( OR = 1.52 and 1.98, respectively). Higher testosterone levels were associated with a decreased likelihood of transitioning to non-excessive drinking ( OR = 0.59). Depression and estradiol levels were not related to transitions in drinking. Conclusions The present study demonstrates that the menopausal transition marks a period of instability in alcohol use among women. Further research is warranted to understand factors related to transitioning in and out of excessive drinking.

The lateral nucleus of the trapezoid body (LNTB) is a prominent nucleus in the superior olivary complex in mammals including humans. Its physiology in vivo is poorly understood due to a paucity of recordings. It is thought to provide a glycinergic projection to the medial superior olive (MSO) with an important role in binaural processing and sound localization. We combined in vivo patch clamp recordings with labeling of individual neurons in the Mongolian gerbil. Labeling of the recorded neurons allowed us to relate physiological properties to anatomy at the light and electron microscopic level. We identified a population of quite dorsally located neurons with surprisingly large dendritic trees on which most of the synaptic input impinges. In most neurons, one or more of these dendrites run through and are then medial to the MSO. These neurons were often binaural and could even show sensitivity to interaural time differences (ITDs) of stimulus fine structure or envelope. Moreover, a subpopulation showed enhanced phase-locking to tones delivered in the tuning curve tail. We propose that these neurons constitute the gerbil main LNTB (mLNTB). In contrast, a smaller sample of neurons was identified that was located more ventrally and that we designate to be in posteroventral LNTB (pvLNTB). These cells receive large somatic excitatory terminals from globular bushy cells. We also identified previously undescribed synaptic inputs from the lateral superior olive. pvLNTB neurons are usually monaural, display a primary-like-with-notch response to ipsilateral short tones at CF and can phase-lock to low frequency tones. We conclude that mLNTB contains a population of neurons with extended dendritic trees where most of the synaptic input is found, that can show enhanced phase-locking and sensitivity to ITD. pvLNTB cells, presumed to provide glycinergic input to the MSO, get large somatic globular bushy synaptic inputs and are typically monaural with short tone responses similar to their primary input from the cochlear nucleus.

Converging clinical and biological evidence suggest sex is an important factor when selecting a pharmacological intervention for smoking cessation. The current investigation used network meta-analyses to estimate sex differences in the comparative efficacy of transdermal nicotine (TN), varenicline, and sustained release (SR) bupropion for smoking cessation. Systematically searched previously published reviews and databases (Medline, PsycINFO, Embase) of randomized, double-blind, placebo-controlled trials of bupropion-SR, TN, and varenicline for cigarette smoking cessation in primary care/general community samples were included. Thirty-two studies met all criteria and 28 (88%) were included in the final analyses, representing 14 389 smokers (51% female). Results of the full sample (women and men combined) mirrored those from a Cochrane Tobacco Addiction Group network meta-analysis of smoking cessation pharmacotherapy, showing VAR>TN=BUP. All medications improved quit rates over placebo for both women and men. Relative to placebo, varenicline efficacy was similar for women and men. Significant sex differences were evident when comparing varenicline versus TN and varenicline versus bupropion. For women, varenicline was more efficacious than TN (RR = 1.41; 95% CI = 1.12,1.76) and bupropion (RR = 1.38; 95% CI = 1.08,1.77). For men, outcomes for those treated with TN and bupropion were similar to those treated with varenicline. There were no differences in efficacy when comparing bupropion versus TN. The advantage of varenicline over bupropion SR and TN is greater for women than men. Clinicians should strongly consider varenicline as the first option treatment for women. Among men, the advantage of varenicline over TN or bupropion is less clear. This study provides information for the sex-informed treatment of nicotine addiction among cigarette smokers. Relative to placebo, women and men achieved similar outcomes when treated with varenicline; however the advantages of varenicline over transdermal patch and bupropion were greater for women compared to men.

Background Stress contributes to the development and maintenance of substance use disorders, with some research suggesting that the impact of stress on substance use disorders is greater in women. However, this has yet to be evaluated in a national dataset, across major substances of abuse. Methods Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n = 36,309), we evaluated relationships among past year stressful life events (0 or 1 vs. 2+ events, range 0–16) and gender, and their association with transitions (new vs. absent cases; ongoing vs. remitted cases) in Diagnostic and Statistical Manual of Mental Disorders Fifth Edition alcohol use disorder, tobacco use disorder, cannabis use disorder, and nonmedical prescription opioid use disorder diagnoses. Results Having two or more stressful life events in the past year increased the odds of having a new alcohol use disorder, tobacco use disorder, cannabis use disorder, and opioid use disorder (OR = 3.14, 2.15, 5.52, and 3.06, respectively) or ongoing alcohol use disorder, tobacco use disorder, and cannabis use disorder (OR = 2.39, 2.62, and 2.95, respectively) compared to zero or one stressful life event. A stress by gender interaction for new vs. absent alcohol use disorder demonstrated that having two or more stressful life events was associated with increased odds of new alcohol use disorder in men (OR = 2.51) and even greater odds of new alcohol use disorder in women (OR = 3.94). Conclusions Results highlight that stress is a robust factor in both men and women with new or ongoing substance use disorders, and that effective treatments for substance use should consider the role of stress in addiction etiology and maintenance. There was little evidence for gender differences in the role of stress on transitions in substance use disorders, except for the onset of alcohol use disorders. Given that rates of alcohol use disorders are increasing in women, the impact of stress needs to be considered.

Women have lower rates of quitting than men with both bupropion and nicotine replacement. It is unknown whether varenicline demonstrates differential efficacy for men and women. The purpose of this study was to conduct the first comprehensive meta-analysis of clinical trial data examining sex differences in the efficacy of varenicline for smoking cessation. Searching MEDLINE, EMBASE, and PsychINFO, 17 of 43 clinical trials of varenicline for smoking cessation published through December 31, 2014 were low-bias randomized double-blind placebo-controlled trials. Data (n = 6710 smokers, 34% female, n = 16 studies, 96% of available data) was analyzed with Metafor program in R. Outcome endpoints were 7-day point-prevalence (PP) and continuous-abstinence (CA) at week 12 (end of treatment), week 24 (6-month follow-up), and week 52 (12-month follow-up). Using placebo, women were less likely than men to quit (PP-12, CA-24; P < .05 for sex). Using varenicline, similar rates of abstinence for men and women were demonstrated for all six outcomes (eg, PP-12 abstinence rates were 53% in both women and men). Varenicline versus placebo outcomes demonstrated that varenicline was more effective for women for short and intermediate outcomes (PP-12, CA-12, CA-24; P < .05 sex × medication interaction). For end-of-treatment PP, varenicline was 46% more effective for women. For continuous abstinence, varenicline was 34% (CA-12) and 31% (CA-24) more effective for women. Unlike other smoking cessation medications, varenicline demonstrated greater efficacy among women smokers for short and immediate-term outcomes and equal efficacy for 1-year outcomes. Varenicline may be particularly useful for reducing the sex disparity typically seen in rates of smoking cessation. Varenicline is currently the most effective FDA-approved smoking cessation medication and this is the first demonstration that women compared with men have a preferred therapeutic response for a smoking cessation medication when considering short-term outcomes. Importantly, this is also the first demonstration that women have similar rates of quitting to men when considering longer-term, 1-year outcomes.