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A segmented Si-telescope and HPGe array, STARS-LIBERACE, was used to study the 156Gd(p, tγ)154Gd direct reaction by particle- γ coincidence spectroscopy. New cross sections with a 25MeV proton beam are reported and compared to previous (p,t) and (t,p) studies. Furthermore, additional evidence for coexisting Kπ=01+,21+ and 02+, 22+ configurations at N = 90 is presented. Direct and indirect population patterns of the low-lying states are also explored. Review of the new and existing evidence favors an interpretation based on a configuration-dependent pairing interaction. The weakening of monopole pairing strength and an increase in quadrupole pairing strength could bring 2p-2h 0 + states below 2 Δ. This may account for a large number of the low-lying 0 + states observed in two-nucleon transfer reactions. A hypothesis for the origin of the 02+ and 03+ states is provided.

The nuclear reactions C12(C12,α)Ne20, C12(C12,p)Na23, and C12(C12,n)Mg23 are the primary reactions in carbon burning, which occurs as part of several stellar processes. The Gamow window, which describes the energy range where most of these reactions take place, is typically around 1.5 MeV in the center-of-mass frame. Direct measurements of the cross sections at this energy are difficult due to the large Coulomb barrier present between the carbon nuclei; however, a successful surrogate measurement can provide the branching ratios between these reactions while avoiding the C12+C12 Coulomb barrier. An experiment was performed using inelastic scattering of 40 MeV α particles on Mg24 as a possible surrogate for the C12+C12 compound nucleus.

Abstract: Mice used in biomedical research are typically housed at ambient temperatures (22°C-24°C) below thermoneutrality (26°C-31°C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. Mice recovered for 21 days in metabolic phenotyping cages at 24°C or 30°C. Regardless of sex or sham/burn treatment, mice housed at 24°C had greater total energy expenditure ( P < 0.001), which was largely attributable to greater basal energy expenditure when compared to mice housed at 30°C ( P < 0.001). Thermoneutral housing (30°C) altered adipose tissue mass in a sex-dependent manner. Compared to sham and small burn groups, large burns resulted in greater water vapor loss, regardless of housing temperature ( P < 0.01). Compared to sham, large burns resulted in greater basal energy expenditure and total energy expenditure in mice housed at 24°C; however, this hypermetabolic response to large burns was blunted in female mice housed at 30°C, and absent in male mice housed at 30°C. Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature ( P < 0.05). Housing at 30°C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Despite progress in smoking reduction in the past several decades, cigarette smoking remains a significant public health concern world-wide, with many smokers attempting but ultimately failing to maintain abstinence. However, little is known about how decision-making evolves in quitting smokers. Based on preregistered hypotheses and analysis plan ( https://osf.io/yq5th ), we examined the evolution of reinforcement learning (RL), a key component of decision-making, in smokers during acute and extended nicotine abstinence. In a longitudinal, within-subject design, we used a probabilistic reward task (PRT) to assess RL in twenty smokers who successfully refrained from smoking for at least 30 days. We evaluated changes in reward-based decision-making using signal-detection analysis and five RL models across three sessions during 30 days of nicotine abstinence. Contrary to our preregistered hypothesis, punishment sensitivity emerged as the only parameter that changed during smoking cessation. While it is plausible that some changes in task performance could be attributed to task repetition effects, we observed a clear impact of the Nicotine Withdrawal Syndrome (NWS) on RL, and a dynamic relationship between craving and reward and punishment sensitivity over time, suggesting a significant recalibration of cognitive processes during abstinence. In this context, the heightened sensitivity to negative outcomes observed at the last session (30 days after quitting) compared to the previous sessions, may be interpreted as a cognitive adaptation aimed at fostering long-term abstinence. While further studies are needed to clarify the mechanisms underlying punishment sensitivity during nicotine abstinence, these results highlight the need for personalized treatment approaches tailored to individual needs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

BACKGROUNDStudies have demonstrated the role of ghrelin in alcohol-related behaviors and consumption. Blockade of the growth hormone secretagogue receptor (GHSR), which is the ghrelin receptor, has been shown to decrease alcohol drinking and reward-related behaviors across several animal models. We previously conducted a human study testing a GHSR inverse agonist/competitive antagonist, PF-5190457, in individuals who are heavy drinkers and showed its safety when coadministered with alcohol. Here, we conducted a phase IIa experimental medicine study in patients with alcohol use disorder (AUD) to investigate the effects of PF-5190457 on alcohol- and food-related outcomes.METHODSForty-two individuals with AUD (n = 29 completers) participated in a randomized, double-blind, placebo-controlled study where they received PF-5190457 100mg b.i.d. (or placebo) in 2 counterbalanced, within-subject stages. Participants completed an alcohol cue-reactivity (CR) experiment in a bar-like laboratory and a virtual food choice experiment in a cafeteria-like virtual reality (VR) environment. A subset of participants (n = 12) performed a CR task during a brain functional MRI (fMRI) experiment.RESULTSPF-5190457 did not reduce cue-elicited alcohol craving. PF-5190457 reduced virtual calories selected (P = 0.04) in the VR environment. PF-5190457 did not influence neural activation during CR task in the fMRI experiment.CONCLUSIONThis study provides human evidence of the role of GHSR blockade in behaviors related to food selection and highlights the need for future investigations into targeting the ghrelin system in AUD.TRIAL REGISTRATIONClinicalTrials.gov (accession no. NCT02707055).FUNDINGNIDA and NIAAA ZIA-DA000635; National Center for Advancing Translational Sciences UH2/UH3-TR000963.

Large-scale brain network function is critical for healthy cognition, yet links between such network function, neurochemistry, and smaller-scale neurocircuitry are unclear. Here, we evaluated 59 healthy individuals using resting-state fMRI to determine how network-level temporal dynamics were impacted by two well-characterized pharmacotherapies targeting catecholamines: methylphenidate (20 mg) and haloperidol (2 mg)-administered via randomized, double-blind, placebo-controlled design. Network temporal dynamic changes were tested for links with drug-induced alterations in complex corticostriatal connections as this circuit is a primary site of action for both drugs. Methylphenidate increased time in the default mode network state (DMN p < 0.001) and dorsal attention network state (DAN p < 0.001) and reduced time in the frontoparietal network state (p < 0.01). Haloperidol increased time in a sensory motor-DMN state (p < 0.01). The magnitude of change in network dynamics induced by methylphenidate vs. placebo correlated with the magnitude of methylphenidate-induced rearrangement of complex corticostriatal connectivity (R = 0.32, p = 0.014). Haloperidol did not alter complex corticostriatal connectivity. Methylphenidate enhanced time in network states involved in internal and external attention (DMN and DAN, respectively), aligning with methylphenidate's established role in attention. Methylphenidate also significantly changed complex corticostriatal connectivity by altering the relative strength between multiple corticostriatal connections, indicating that methylphenidate may shift which corticostriatal connections are prioritized relative to others. Findings show that these corticostriatal circuit changes are linked with large-scale network temporal dynamics. Collectively, these findings provide a deeper understanding of large-scale network function, set a stage for mechanistic understanding of network engagement, and provide useful information to guide medication use based on network-level effects. Trial Registration: Registry name: ClinicalTrials.gov; URL: Brain Networks and Addiction Susceptibility-Full Text View-ClinicalTrials.gov; URL Plain text: https://classic.clinicaltrials.gov/ct2/show/NCT01924468; Identifier: NCT01924468., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear., Methods: The current study is a longitudinal investigation with 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study at ages 9 to 10 years at the onset of the study. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multidomain behavioral assessments including cognitive functions and psychopathological measures. For the latent resting-state functional connectivity factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using 2-year follow-up data, and its genetic association was evaluated using twin data from the same cohort., Results: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multidomain behavioral assessments (5-fold cross-validation: ρ = 0.68-0.73 for the training set [n = 5096]; ρ = 0.56-0.58 for the test set [n = 1476]). This functional connectome pattern was highly heritable (h 2  = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with the cumulative number of psychiatric disorders assessed concurrently and at 2 years post-magnetic resonance imaging scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period., Conclusions: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in the development of psychiatric disorders during early adolescence., (Published by Elsevier Inc.)

Importance: Identifying brain-based markers of resiliency that reliably predict who is and is not at elevated risk for developing psychopathology among children who experience adverse childhood experiences (ACEs) is important for improving our mechanistic understanding of these etiological links between child adversity and psychopathology and guiding precision medicine and prevention efforts for reducing psychiatric impact of ACEs., Objective: To examine associations between ACEs and transdiagnostic psychopathology during the transition from preadolescence to early adolescence and test whether these associations are moderated by a hypothesized resilience factor, a previously identified connectome variate (CV) that is associated with higher cognitive function and lower psychopathology., Design Setting and Participants: This study was conducted in a longitudinal design based on multicenter data from a community cohort of U.S. youth aged of 9-11 at baseline, who participated in the Adolescent Brain Cognitive Development (ABCD) study (N=7,382 at baseline and 6,813 at 2-year follow-up). Linear regression models and moderation analyses were used to characterize concurrent and prospective associations between lifetime ACEs and number of DSM-5 psychiatric disorders (indexing transdiagnostic psychopathology) and to determine if individual variations in these associations were moderated by the CV derived from resting-state fMRI at baseline., Main Outcomes and Measures: Cumulative number of current DSM-5 psychiatric disorders assessed using the computerized self-admin version Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) and lifetime ACEs assessed from child and parent reports at baseline (9-10 years) and 2-year-follow-up (11-12 years)., Results: ACE total scores correlated positively with the cumulative number of current DSM-5 psychiatric disorders at both baseline ( r =.258, p < .001) and 2-year follow-up ( r =.257, p < .001). The baseline CV score moderated the ACE-disorder associations at baseline (B = -0.021, p < .001) and at 2-year follow-up (B = -0.018, p = .008), as well as the association between the changes in ACE and in the number of disorders from baseline to year 2 (B = -0.012, p = .045). Post-hoc analyses further showed that the moderation effect of CV on ACE-psychopathology associations was specific to the threat-related ACEs and to female youth., Conclusions and Relevance: These findings provide preliminary evidence for a connectome-based resiliency marker and suggest that functional connectivity strength in a broad system including frontal-parietal cortices and subcortical nuclei relevant to cognitive control may protect preadolescents who have experienced lifetime ACEs--especially females and those experiencing threat-related ACEs--from developing transdiagnostic psychopathology.

Background: We investigated a potential sex difference in the relationship between alcohol consumption, brain age gap and cognitive function in older adults without cognitive impairment from the population-based Mayo Clinic Study of Aging., Methods: Self-reported alcohol consumption was collected using the food-frequency questionnaire. A battery of cognitive testing assessed performance in four different domains: attention, memory, language, and visuospatial. Brain magnetic resonance imaging (MRI) was conducted using 3-T scanners (Signa; GE Healthcare). Brain age was estimated using the Brain-Age Regression Analysis and Computational Utility Software (BARACUS). We calculated the brain age gap as the difference between predicted brain age and chronological age., Results: The sample consisted of 269 participants [55% men (n=148) and 45% women (n=121) with a mean age of 79.2 ± 4.6 and 79.5 ± 4.7 years respectively]. Women had significantly better performance compared to men in memory, (1.12 ± 0.87 vs 0.57 ± 0.89, P<0.0001) language (0.66 ± 0.8 vs 0.33 ± 0.72, P=0.0006) and attention (0.79 ± 0.87 vs 0.39 ± 0.83, P=0.0002) z-scores. Men scored higher in visuospatial skills (0.71 ± 0.91 vs 0.44 ± 0.90, P=0.016). Compared to participants who reported zero alcohol drinking (n=121), those who reported alcohol consumption over the year prior to study enrollment (n=148) scored significantly higher in all four cognitive domains [memory: F 3,268  = 5.257, P=0.002, Language: F 3,258  = 12.047, P<0.001, Attention: F 3,260  = 22.036, P<0.001, and Visuospatial: F 3,261  = 9.326, P<0.001] after correcting for age and years of education. In addition, we found a significant positive correlation between alcohol consumption and the brain age gap (P=0.03). Post hoc regression analysis for each sex with language z-score revealed a significant negative correlation between brain age gap and language z-scores in women only (P=0.008)., Conclusion: Among older adults who report alcohol drinking, there is a positive association between higher average daily alcohol consumption and accelerated brain aging despite the fact that drinkers had better cognitive performance compared to zero drinkers. In women only, accelerated brain aging is associated with worse performance in language cognitive domain. Older adult women seem to be vulnerable to the negative effects of alcohol on brain structure and on certain cognitive functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abulseoud, Caparelli, Krell‐Roesch, Geda, Ross and Yang.)

Tar spot, caused by Phyllachora maydis , is the most significant yield-limiting disease of corn ( Zea mays L.) in Indiana. Currently, fungicides are an effective management tool for this disease, and partial returns from their use under different disease severity conditions has not previously been studied. Between 2019 and 2021, two separate field experiments were conducted in each year in Indiana to assess the efficacy of nine foliar fungicide products and nine fungicide application timings based on corn growth stages on tar spot symptoms and stromata, canopy greenness, yield, and influence on partial returns. All fungicides evaluated significantly suppressed tar spot development in the canopy and increased canopy greenness over the nontreated control. Additionally, applications of mefentrifluconazole + pyraclostrobin, metconazole + pyraclostrobin, cyproconazole + picoxystrobin at tassel, and propiconazole + benzovindiflupyr + azoxystrobin between the tassel and dough growth stages were the most effective at significantly reducing disease severity, increasing canopy greenness, protecting yield, and offered the greatest partial return. Fungicide products varied in their ability to protect yield under low and high disease severity conditions relative to the nontreated control. Consistently, positive yield increases were observed when disease severity was high, which translated to greater profitability relative to low severity conditions. On average, the yield increases across foliar fungicide products and timed application treatments were 544.6 and 1,020.7 kg/ha greater, and partial returns using a grain value of $0.17/kg were $92.6/ha and $173.5/ha greater, respectively, when high severity conditions occurred. This research demonstrates that foliar fungicides and appropriately timed fungicide applications can profitably be used to manage tar spot in Indiana under high disease severity conditions., Competing Interests: The author(s) declare no conflict of interest.

Importance: Temporal dynamic measures provide insight into the neurobiological properties of nicotine use. It is critical to determine whether brain-based measures are associated with substance use risk factors, such as childhood trauma-related emotion dysregulation., Objective: To assess temporal dynamic differences based on smoking status and examine the associations between childhood trauma, alexithymia, nicotine smoking, and default mode network (DMN) states., Design, Setting, and Participants: This cross-sectional study was conducted in the Baltimore, Maryland, area at the National Institute on Drug Abuse. Participants included individuals aged 18 to 65 years who smoked nicotine long term and matched controls with no co-occurring substance use or psychiatric disorders. Participants were enrolled from August 8, 2013, to August 9, 2022. Analysis was conducted from August 2022 to July 2023., Exposure: Long-term nicotine smoking., Main Outcomes and Measures: The main outcome was temporal dynamic differences based on smoking status. Coactivation pattern analysis was conducted based on 16-minute resting-state functional magnetic resonance imaging; total time in, persistence of, and frequency of transitions into states were evaluated. The associations between childhood trauma (Childhood Trauma Questionnaire), alexithymia (20-item Toronto Alexithymia Scale), and DMN temporal dynamics were assessed., Results: The sample included 204 participants (102 individuals who smoked nicotine and 102 control individuals) with a mean (SD) age of 37.53 (10.64) years (109 [53.4%] male). Compared with controls, individuals who smoked nicotine spent more time in the frontoinsular DMN (FI-DMN) state (mean difference, 25.63 seconds; 95% CI, 8.05-43.20 seconds; η2p = 0.04; P = .004 after Bonferroni correction). In those who smoked nicotine, greater alexithymia was associated with less time spent in the FI-DMN state (r, -0.26; 95% CI, -0.44 to -0.07; P = .007). In a moderated mediation analysis, alexithymia mediated the association between childhood trauma and time spent in the FI-DMN state only in individuals who smoked nicotine (c' = -0.24; 95% CI, -0.58 to -0.03; P = .02)., Conclusions and Relevance: Compared with controls, individuals who smoked nicotine spent more time in the FI-DMN state. Among those who smoked nicotine, childhood trauma-related alexithymia was associated with less time spent in the FI-DMN state, indicating that considering trauma-related factors may reveal alternative neurobiological underpinnings of substance use. These data may aid in reconciling contradictory findings in prior literature regarding the role of FI-DMN regions in substance use.

Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing regions of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate mean ambient temperature (18-23 °C) were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics., (© 2023. Springer Nature Limited.)

Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency, ω , in addition to the diffusion tensor, D , and relaxation, R 1 , R 2 , correlations. A D ( ω ) - R 1 - R 2 clinical imaging protocol was then introduced, with limited brain coverage and 3 mm 3 voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse in vivo MD-MRI acquisition protocol providing whole brain coverage at 2 mm 3 voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their D ( ω ) - R 1 - R 2 distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.

Introduction: Tar spot is a high-profile disease, causing various degrees of yield losses on corn ( Zea mays L.) in several countries throughout the Americas. Disease symptoms usually appear at the lower canopy in corn fields with a history of tar spot infection, making it difficult to monitor the disease with unmanned aircraft systems (UAS) because of occlusion., Methods: UAS-based multispectral imaging and machine learning were used to monitor tar spot at different canopy and temporal levels and extract epidemiological parameters from multiple treatments. Disease severity was assessed visually at three canopy levels within micro-plots, while aerial images were gathered by UASs equipped with multispectral cameras. Both disease severity and multispectral images were collected from five to eleven time points each year for two years. Image-based features, such as single-band reflectance, vegetation indices (VIs), and their statistics, were extracted from ortho-mosaic images and used as inputs for machine learning to develop disease quantification models., Results and Discussion: The developed models showed encouraging performance in estimating disease severity at different canopy levels in both years (coefficient of determination up to 0.93 and Lin's concordance correlation coefficient up to 0.97). Epidemiological parameters, including initial disease severity or y 0 and area under the disease progress curve, were modeled using data derived from multispectral imaging. In addition, results illustrated that digital phenotyping technologies could be used to monitor the onset of tar spot when disease severity is relatively low (< 1%) and evaluate the efficacy of disease management tactics under micro-plot conditions. Further studies are required to apply and validate our methods to large corn fields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Lane, Fernández-Campos, Cruz-Sancan, Lee, Gongora-Canul, Ross, Da Silva, Telenko, Goodwin, Scofield, Oh, Jung and Cruz.)

Cancer continues to be a significant source of mortality and morbidity worldwide despite progress in cancer prevention, early detection, and treatment. Fortunately, immunotherapy has been a breakthrough in the treatment of many cancers. However, the response to immunotherapy treatment and the experience of associated side effects varies significantly between patients. Recently, attention has been given to understanding the role of the tumor immune microenvironment (TIME) in the development, progression, and treatment response of cancer. A new understanding of the role of the microbiota in the modulation of the TIME has further complicated the story but also unlocked a new area of adjuvant therapeutic research. The complex balance of tumor-permissive and tumor-suppressive immune environments requires further elucidation in order to be harnessed as a therapeutic target. Because both the TIME and the microbiome show importance in these areas, we propose here the concept of the "microbiome-TIME axis" to review the current field of research and future directions.

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.

Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological data increasingly show that striatal nodes receive appreciable input from numerous cortical areas, and that the combinational properties of these multivariate "connectivity profiles" play a predominant role in shaping striatal activity and function. Yet, how abnormal configuration of striatal connectivity profiles might contribute to SUD is unknown. Here, we implemented a novel "connectivity profile analysis" (CPA) approach using resting-state functional connectivity data to facilitate detection of different types of connectivity profile "misconfiguration" that may reflect distinct forms of aberrant circuit plasticity in SUD. We examined 46 nicotine-dependent smokers and 33 non-smokers and showed that both dorsal striatum (DS) and ventral striatum (VS) connectivity profiles with frontal cortex were misconfigured in smokers-but in doubly distinct fashions. DS misconfigurations were stable across sated and acute abstinent states (indicative of a "trait" circuit adaptation) whereas VS misconfigurations emerged only during acute abstinence (indicative of a "state" circuit adaptation). Moreover, DS misconfigurations involved abnormal connection strength rank order arrangement, whereas VS misconfigurations involved abnormal aggregate strength. We found that caudal ventral putamen in smokers uniquely displayed multiple types of connectivity profile misconfiguration, whose interactive magnitude was linked to dependence severity, and that VS misconfiguration magnitude correlated positively with withdrawal severity during acute abstinence. Findings underscore the potential for approaches that more aptly model the neurobiological composition of corticostriatal circuits to yield deeper insights into the neural basis of SUD., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are notably heterogeneous, suggesting underlying endophenotypic variance. However, parsing this variance in smokers has remained challenging. In this study, we identified smoker subgroups based on response accuracy during a Parametric Flanker Task (PFT) and then characterized distinct neuroimaging endophenotypes using a nicotine state manipulation. Smokers completed the PFT in two fMRI sessions (nicotine sated, abstinent). Based on response accuracy in the stressful, high cognitive demand PFT condition, smokers split into high (HTP, n = 21) and low task performer (LTP, n = 24) subgroups. Behaviorally, HTPs showed greater response accuracy (88.68% ± 5.19 SD) vs. LTPs (51.04% ± 4.72 SD), independent of nicotine state, and greater vulnerability to abstinence-induced errors of omission (EOm, p = 0.01). Neurobiologically, HTPs showed greater BOLD responses in attentional control brain regions, including bilateral insula, dorsal ACC, and frontoparietal Cx for the [correct responses (-) errors of commission] PFT contrast in both states. A whole-brain functional connectivity (FC) analysis with these subgroup-derived regions as seeds identified two circuits: Precentral Cx↔Insula and Insula↔Occipital Cx, with abstinence-induced FC strength increases seen only in HTPs. Finally, abstinence-induced FC and behavior (EOm) differences were positively correlated for HTPs in a Precentral Cx↔Orbitofrontal cortical circuit. In sum, only the HTP subgroup demonstrated sustained attention deficits following 48-hr nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this 'dual (task and abstinence) stressor' approach revealed discrete smoker subgroups with differential attentional deficits to withdrawal that could be novel pharmacological/behavioral targets for therapeutic interventions to improve cessation outcomes., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci's hemispheric connection profiles and its spatial variance across the striatum, and assessment of how interindividual differences relate to function, stands to further the understanding of the role of corticostriatal circuits in lateralized functions and the role of abnormal corticostriatal laterality in neurodevelopmental and other neuropsychiatric disorders. A resting-state functional connectivity fingerprinting approach (n = 261) identified "laterality hotspots"-loci whose profiles of connectivity with ipsilateral and contralateral frontal cortex were disproportionately dissimilar-in the right rostral ventral putamen, left rostral central caudate, and bilateral caudal ventral caudate. Findings were replicated in an independent sample and were robust to both preprocessing choices and the choice of cortical atlas used for parcellation definitions. Across subjects, greater rightward connectional laterality at the right ventral putamen hotspot and greater leftward connectional laterality at the left rostral caudate hotspot were associated with higher performance on tasks engaging lateralized functions (i.e., response inhibition and language, respectively). In sum, we find robust and reproducible evidence for striatal loci with disproportionately lateralized connectivity profiles where interindividual differences in laterality magnitude are associated with behavioral capacities on lateralized functions., (Published by Oxford University Press 2021.)

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2 n = 62). Lesion locations were mapped to a brain atlas and the brain network functionally connected to each lesion location was computed using human connectome data (n = 1,000). Associations with addiction remission were identified. Generalizability was assessed using an independent cohort of patients with focal brain damage and alcohol addiction risk scores (n = 186). Specificity was assessed through comparison to 37 other neuropsychological variables. Lesions disrupting smoking addiction occurred in many different brain locations but were characterized by a specific pattern of brain connectivity. This pattern involved positive connectivity to the dorsal cingulate, lateral prefrontal cortex, and insula and negative connectivity to the medial prefrontal and temporal cortex. This circuit was reproducible across independent lesion cohorts, associated with reduced alcohol addiction risk, and specific to addiction metrics. Hubs that best matched the connectivity profile for addiction remission were the paracingulate gyrus, left frontal operculum, and medial fronto-polar cortex. We conclude that brain lesions disrupting addiction map to a specific human brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation., (© 2022. The Author(s).)

A randomized neonatal piglet trial was conducted to evaluate the safety and the effects of a plant-based formula containing almonds and buckwheat as the main ingredients on growth and plasma parameters. From postnatal day (PND) 2 to 21, the piglets were fed a dairy-based milk formula (Similac Advance) or a plant-based formula (Else Nutrition) and all piglets were euthanized at day 21. No diarrhea was observed after PND 8 and all the piglets completed the trial. Body growth, kcal intake, the complete plasma count parameters and hematological parameters were within the reference range in both groups. Organ growth and development was similar between the two groups. Plasma glucose was higher in the dairy-based-fed piglets relative to the plant-based at 2 weeks of age. Liver function biomarkers levels were greater in the plasma of the plant-based compared to the dairy-based fed group. In addition, calcium levels were higher in the plant-based fed piglets at 1 week of age. Thus, the plant-based formula tested in this study was well tolerated by the piglets and supported similar growth compared to dairy-based milk formula. Therefore, the results support the safety of the tested plant-based infant formula during the neonatal period in comparison to the dairy-based formula fed group.

Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults [n = 240, mean age 35.1 (±10.7) years, 48% male, 49% African American]. Accelerated brain aging was operationalized as the difference between predicted and chronological age ("brain age gap"). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap (β = 0.014, p = 0.023). We replicated these results in an independent cohort [n = 231 adults, mean age 34.3 (±11.1) years, 55% male, 28% African American: β = 0.014, p = 0.002]. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated., (Copyright © 2021. Published by Elsevier Inc.)

Delirium is a common neurocognitive disorder in hospitalised older adults with substantial negative consequences. Impaired global cognition is a well-established delirium risk factor. However, poor performance on attention tests and higher intra-subject variability may be more sensitive delirium risk factors, given the disorder is characterised by a fluctuating course and attentional deficits. We systematically searched databases (Embase, PsycINFO, MEDLINE) and 44 studies satisfied inclusion criteria. Random-effects meta-analysis models showed poor performance in all cognitive domains except perception was significantly associated with incident delirium. Largest effects were for orientation (g=-1.20) and construction and motor performance (g=-0.60). These effects were no longer significant in the subgroup without pre-existing cognitive impairment, where executive functions and verbal functions and language skills were associated with incident delirium. A small, non-significant association between intra-subject variability and incident delirium was found (g=0.42). Cognitive domain specific tests may be quicker and more sensitive predictors of incident delirium. This pattern of neuropsychological findings supports the proposition that vulnerability for delirium manifests as a dysfunction of whole-brain information integration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recent evidence suggests that the aberrant signaling of salience is associated with psychotic illness. Salience, however, can take many forms in task environments. For example, salience may refer to any of the following: (1) the valence of an outcome, (2) outcomes that are unexpected, called reward prediction errors (PEs), or (3) cues associated with uncertain outcomes. Here, we measure brain responses to different forms of salience in the context of a passive PE-signaling task, testing whether patients with schizophrenia (SZ) showed aberrant signaling of particular types of salience. We acquired event-related MRI data from 29 SZ patients and 23 controls during the performance of a passive outcome prediction task. Across groups, we found that the anterior insula and posterior parietal cortices were activated to multiple different types of salience, including PE magnitude and heightened levels of uncertainty. However, BOLD activation to salient events was not significantly different between patients and controls in many regions, including the insula, posterior parietal cortices, and default mode network nodes. Such results suggest that deficiencies in salience processing in SZ may not result from an impaired ability to signal salience per se , but instead the ability to use such signals to guide future actions. Notably, no between-group differences were observed in BOLD signal changes associated with PE-signaling in the striatum. However, positive symptom severity was found to significantly correlate with the magnitudes of salience contrasts in default mode network nodes. Our results suggest that, in an observational environment, SZ patients may show an intact ability to activate striatal and cortical regions to rewarding and non-rewarding salient events. Furthermore, reduced deactivation of a hypothesized default mode network node for SZ participants with high levels of positive symptoms, following salient events, point to abnormalities in interactions of the salience network with other brain networks, and their potential importance to positive symptoms.

Background: The nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS., Methods: To isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain., Results: During abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms., Conclusions: Using multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence., (Published by Elsevier Inc.)

Rationale: Previous neuroimaging studies of cognition involving nicotinic acetylcholine receptor (nAChR) agonist administration have repeatedly found enhanced task-induced deactivation of regions of the default mode network (DMN), a group of brain systems that is more active at rest and mediates task-independent thought processes. This effect may be related to pro-cognitive nAChR agonist effects OBJECTIVES: The present study sought to test whether nAChR modulation of the DMN is bi-directional, i.e., whether a nAChR antagonist would reduce task-induced deactivation., Methods: Eighteen healthy non-smokers underwent functional magnetic resonance imaging while performing a letter N-back task. Scans were performed after nicotine administration (7 mg/24 h, transdermally), after administration of the nAChR antagonist mecamylamine (7.5 mg, p.o.), and after double placebo, in counterbalanced sequence. Blood-oxygen-level-dependent (BOLD) signal was analyzed within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC) regions of interest-central hubs of the DMN in which consistent nAChR agonist-induced changes had previously been identified., Results: Nicotine enhanced hit rate in both the 0-back and 2-back condition, while mecamylamine slowed reaction time in the 2-back condition. Mecamylamine reduced task-induced deactivation of vmPFC and PCC. Nicotine had no significant effects on the BOLD signal., Conclusions: The finding that nAChR tone reduction by mecamylamine weakened task-induced DMN deactivation indicates that a constant tone of nAChR activation helps regulate DMN activity in healthy individuals. This suggests that low nAChR tone may play a causal role in DMN dysregulation seen in conditions such as mild cognitive impairment or Alzheimer's disease.

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges' g = 0.24, 95% CI 0.06-0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children.

Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42020149276.

Tar spot of corn has been a major foliar disease in several Latin American countries since 1904. In 2015, tar spot was first documented in the United States and has led to significant yield losses of approximately 4.5 million t. Tar spot is caused by an obligate pathogen, Phyllachora maydis, and thus requires a living host to grow and reproduce. Due to its obligate nature, biological and epidemiological studies are limited and impact of disease in corn production has been understudied. Here we present the current literature and gaps in knowledge of tar spot of corn in the Americas, its etiology, distribution, impact and known management strategies as a resource for understanding the pathosystem. This will in tern guide current and future research and aid in the development of effective management strategies for this disease.

Most cigarette smokers who wish to quit too often relapse within the first few days of abstinence, primarily due to the aversive aspects of the nicotine withdrawal syndrome (NWS), which remains poorly understood. Considerable research has suggested that the dorsal anterior cingulate cortex (dACC) plays a key role in nicotine dependence, with its functional connections between other brain regions altered as a function of trait addiction and state withdrawal. The flow of information between dACC and fronto-striatal regions is secured through different pathways, the vast majority of which are glutamatergic. As such, we investigated dACC activity using resting state functional connectivity (rsFC) with functional magnetic resonance imaging (fMRI) and glutamate (Glu) concentration with magnetic resonance spectroscopy (MRS). We also investigated the changes in adenosine levels in plasma during withdrawal as a surrogate for brain adenosine, which plays a role in fine-tuning synaptic glutamate transmission. Using a double-blind, placebo-controlled, randomized crossover design, nontreatment seeking smoking participants (N = 30) completed two imaging sessions, one while nicotine sated and another after 36 h nicotine abstinence. We observed reduced dACC Glu (P = 0.029) along with a significant reduction in plasma adenosine (P = 0.03) and adenosine monophosphate (AMP; P < 0.0001) concentrations during nicotine withdrawal in comparison with nicotine sated state. This withdrawal state manipulation also led to an increase in rsFC strength (P < 0.05) between dACC and several frontal cortical regions, including left superior frontal gyrus (LSFG), and right middle frontal gyrus (RMFG). Moreover, the state-trait changes in dACC Glu and rsFC strength between the dACC and both SFG and MFG were positively correlated (P = 0.012, and P = 0.007, respectively). Finally, the change in circuit strength between dACC and LSFG was negatively correlated with the change in withdrawal symptom manifestations as measured by the Wisconsin Smoking Withdrawal Scale (P = 0.04) and Tobacco Craving Questionnaire (P = 0.014). These multimodal imaging-behavioral findings reveal the complex cascade of changes induced by acute nicotine deprivation and call for further investigation into the potential utility of adenosine- and glutamate-signaling as novel therapeutic targets to treat the NWS.

The size of a ΔK=0 M1 excitation strength has been determined for the first time in a predominantly axially deformed even-even nucleus. It has been obtained from the observation of a rare K-mixing situation between two close-lying J^{π}=1^{+} states of the nucleus ^{164}Dy with components characterized by intrinsic projection quantum numbers K=0 and K=1. Nuclear resonance fluorescence induced by quasimonochromatic linearly polarized γ-ray beams provided evidence for K mixing of the 1^{+} states at 3159.1(3) and 3173.6(3) keV in excitation energy from their γ-decay branching ratios into the ground-state band. The ΔK=0 transition strength of B(M1;0&#95;{1}^{+}→1&#95;{K=0}^{+})=0.008(1)μ&#95;{N}^{2} was inferred from a mixing analysis of their M1 transition rates into the ground-state band. It is in agreement with predictions from the quasiparticle phonon nuclear model. This determination represents first experimental information on the M1 excitation strength of a nuclear quantum state with a negative R-symmetry quantum number.

Changes to cognition, both decline and improvement, are commonly reported after transcatheter aortic valve implantation (TAVI). However, previous systematic reviews and meta-analyses have missed these subgroups by assessing whole-group-averages for cognitive outcomes. We sought to pool estimates to identify the prevalence of cognitive decline and improvement after TAVI, as well as associated factors for these outcomes. A systematic review identified 15 articles appropriate for meta-analysis. When robust cognitive change definitions were employed, the pooled prevalence of incident cognitive impairment up to 1-, 1 to 6-, and ≥6-months post-TAVI was 7%, 14%, and 12%, respectively. For cognitive improvement, the prevalence from 1 to 6 months and ≥6 months after TAVI was estimated to be 19% and 11%, respectively. Two factors were associated with these cognitive outcomes: (1) using a cerebral embolic protection device was associated with decreased prevalence of cognitive decline up to 1-week post-TAVI; (2) baseline cognitive impairment had a large association with post-TAVI cognitive improvement. In conclusion, cognitive decline and cognitive improvement are experienced by approximately 7% to 19% of patients after TAVI, respectively. Those with the lowest cognitive performance pre-TAVI appear to have the most to gain in terms of cognitive improvement post-TAVI. Identifying further predictive factors for cognitive decline and improvement post-TAVI will facilitate a personalized-medicine approach for cognitive care and prognosis., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Phyllachora maydis is an important fungal pathogen that causes tar spot of corn and has led to significant yield loss in the United States and other countries. P. maydis is an obligate biotroph belonging to the Sordariomycetes class of Ascomycota. Due to the challenges posed by their obligate nature, there is no genome sequence available in the Phyllachora genus. P. maydis isolate PM01 was collected from a corn field in Indiana and the genome was determined by next-generation sequencing. The assembly size is 45.7 Mb, with 56.46% repetitive sequences. There are 5,992 protein-coding genes and 59 are predicted as effector proteins. This genome resource will increase our understanding of genomic features of P. maydis and will assist in studying the corn - P. maydis interaction and identifying potential resistant candidates for corn breeding programs.

Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here we examine the effects of nicotine dependence (trait; smokers (n = 24) vs. non-smoking controls; n = 20) and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of inhibitory control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence, and pharmacological manipulation. However, effects were driven entirely by conditions that required less inhibitory control. When demand for inhibitory control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

Background: The nicotine withdrawal syndrome remains a major impediment to smoking cessation. Cognitive and affective disturbances are associated with altered connectivity within and between the executive control network, default mode network (DMN), and salience network. We hypothesized that functional activity in cognitive control networks, and downstream amygdala circuits, would be modified by application of transcranial direct current stimulation (tDCS) to the left (L) dorsolateral prefrontal cortex (dlPFC, executive control network) and right (R) ventromedial prefrontal cortex (vmPFC, DMN)., Methods: A total of 15 smokers (7 women) and 28 matched nonsmokers (14 women) participated in a randomized, sham-controlled, double-blind, exploratory crossover study of 3 tDCS conditions: anodal-(L)dlPFC/cathodal-(R)vmPFC, reversed polarity, and sham. Cognitive tasks probed withdrawal-related constructs (error monitoring, working memory, amygdalar reactivity), while simultaneous functional magnetic resonance imaging measured brain activity. We assessed tDCS impact on trait (nonsmokers vs. sated smokers) and state (sated vs. abstinent) smoking aspects., Results: Single-session, anodal-(L)dlPFC/cathodal-(R)vmPFC tDCS enhanced deactivation of DMN nodes during the working memory task and strengthened anterior cingulate cortex activity during the error-monitoring task. Smokers were more responsive to tDCS-induced DMN deactivation when sated (vs. withdrawn) and displayed greater cingulate activity during error monitoring than nonsmokers. Nicotine withdrawal reduced task engagement and attention and reduced suppression of DMN nodes., Conclusions: Cognitive circuit dysregulation associated with nicotine withdrawal may be modifiable by anodal tDCS applied to L-dlPFC and cathodal tDCS applied to R-vmPFC. tDCS may have stronger effects as a complement to existing therapies, such as nicotine replacement, owing to possible enhanced plasticity in the sated state., (Published by Elsevier Inc.)

Distress tolerance (DT), a predictor of substance use treatment retention and post-treatment relapse, is associated with task based neural activation in regions located within the salience (SN), default mode (DMN), and executive control networks (ECN). The impact of network connectivity on DT has yet to be investigated. The aim of the present study was to test within and between network resting-state functional connectivity (rsFC) associations with DT, and the impact of cocaine use on this relationship. Twenty-nine adults reporting regular cocaine use (CU) and 28 matched healthy control individuals (HC), underwent resting-state functional magnetic resonance imaging followed by the completion of two counterbalanced, computerized DT tasks. Dual-regression analysis was used to derive within and between network rsFC of the SN, DMN, and lateralized (left and right) ECN. Cox proportional-hazards survival models were used to test the interactive effect of rsFC and group on DT. The association between cocaine use severity, rsFC, and DT was tested within the CU group. Lower LECN and higher DMN-SN rsFC were associated with DT impairment. Greater amount of cocaine use per using day was associated with greater DMN-SN rsFC. The findings emphasize the role of neural resource allocation within the ECN and between DMN-SN on distress tolerance., Competing Interests: The authors declare no conflicts of interest.

There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD., (Copyright © 2019 Steele, Maxwell, Ross, Stein and Salmeron.)

The habenula, an epithalamic nucleus involved in reward and aversive processing, may contribute to negative reinforcement mechanisms maintaining nicotine use. We used a performance feedback task that differentially activates the striatum and habenula and administered nicotine and varenicline (versus placebos) to overnight-abstinent smokers and nonsmokers to delineate feedback-related functional brain alterations both as a function of smoking trait (smokers versus nonsmokers) and drug administration state (drug versus placebo). Smokers showed less striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with trait-level addiction severity. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers, and increased habenula activity among smokers correlated with elevated state-level tobacco cravings. These outcomes highlight a dissociation between neurobiological processes linked with the dependence severity trait and the nicotine withdrawal state. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Latest developments in magnetic resonance imaging (MRI) hardware and software have significantly improved image acquisition for functional MRI (fMRI) techniques, including resting-state fMRI (rsfMRI). Specifically, with improvements in gradient and radiofrequency coils and advances in pulse sequence designs, functional images with higher spatiotemporal resolution can be achieved. However, while smaller voxel size has the benefit of resolving finer brain structures, it also decreases voxel-wise signal-to-noise ratio (SNR) and, subsequently, temporal SNR (tSNR), which is critical for the sensitivity of fMRI. Although the improved temporal resolution allows more image frames to be collected per unit time, the ability to detect brain activity by using the high spatiotemporal fMRI has not been fully characterized. Here, we aimed to evaluate the effects of spatial smoothing, scan length, sample size, seed size, and location on resting-state functional connectivity (rsFC) and tSNR by using data from the human connectome project. Results from this analysis show an important effect of smoothing on the rsFC strength (correlation values between the seed and the target) as well as on the tSNR. In contrast, while rsFC strength is not affected by sample size, the standard error decreases with the increasing number of participants, therefore improving the detection power for larger samples. Scan length and seed size seem to have a moderate effect on rsFC strength. Finally, seed location has an important impact on rsFC maps, as rsFC strength from cortical seeds seems higher than from sub-cortical seeds. In summary, our findings show that the choice of parameters can be critical for an rsfMRI study.