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The majority of studies on the relationship between cancer and well-being have been conducted in the United States and other Western countries. Consequently, a bias might exist that ignores the influence of cultural factors on perceptions of cancer, its etiology, and treatment. This investigation, a pilot study using African languages, attempted to explore the impacts of culture on health-related quality of life by using Celia's FACT-G scales to study rural Zulu, Pedi, and Tswana patients of extremely low socioeconomic status. Results suggest that cultural factors may exert a significant influence on the experience of FACT-G measured quality-of-life issues for cancer patients. Specifically, cultural attitudes toward accepting fate, a high level of trust and deference to healers, and a highly collectivistic orientation surrounding treatment decisions and procedures may have had an impact on the patient's scores on all four FACT-G subscales. [ABSTRACT FROM AUTHOR]

Background: While deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) of thalamus or posterior subthalamic area (PSA) can suppress forms of action tremor in people with Essential Tremor, previous studies have suggested postural tremor may respond more robustly than kinetic tremor to DBS., Objectives: In this study, we aimed to more precisely quantify the (1) onset/offset dynamics and (2) steady-state effects of VIM/PSA-DBS on postural and kinetic tremor., Methods: Tremor data from wireless inertial measurement units were collected from 11 participants with ET (20 unilaterally assessed DBS leads). Three postural hold tasks and one kinetic task were performed with stimulation turned off, in 2-min intervals after enabling unilateral DBS at the clinician-optimized DBS setting (15 min), and in 2-min intervals following cessation of DBS (5 min)., Results: At baseline, kinetic tremor had significantly higher amplitudes, standard deviation, and frequency than postural tremor (P < 0.001). DBS had a more robust acute effect on postural tremors (54% decrease, P < 0.001), with near immediate tremor suppression in amplitude and standard deviation, but had non-significant improvement of kinetic tremor on the population-level across the wash-in period (34% decrease). Tremor response was not equivalent between wash-in and wash-out timepoints and involved substantial individual variability including task-specific rebound or long wash-out effects., Conclusions: Programming strategies for VIM/PSA-DBS should consider the individual temporal and effect size variability in postural versus kinetic tremor improvement. Improved targeting and programming strategies around VIM and PSA may be necessary to equivalently suppress both postural and kinetic tremors., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Theoretical and methodological research on threat conditioning provides important neuroscience-informed approaches to studying fear and anxiety. The threat conditioning framework is at the vanguard of physiological and neurobiological research into core mechanistic symptoms of anxiety-related psychopathology, providing detailed models of neural circuitry underlying variability in clinically relevant behaviors (e.g., decreased extinction, heightened generalization) and heterogeneity in clinical anxiety presentations. Despite the strengths of this approach in explaining symptom and syndromal heterogeneity, the vast majority of psychopathology-oriented threat conditioning work has been conducted using Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic categories, which fail to capture the symptom-level resolution that is afforded by threat conditioning indices. Furthermore, relations between fine-grained neurobehavioral measures of threat conditioning and anxiety traits and symptoms are substantially attenuated by within-category heterogeneity, arbitrary boundaries, and inherent comorbidity in the DSM approach. Conversely, the Hierarchical Taxonomy of Psychopathology (HiTOP) is a promising approach for modeling anxiety symptoms relevant to threat conditioning work and for relating threat conditioning to broader anxiety-related constructs. To date, HiTOP has had a minimal impact on the threat conditioning field. Here, we propose that combining the HiTOP and neurobehavioral threat conditioning approaches is an important next step in studying anxiety-related pathology. We provide a brief review of prominent DSM critiques and how they affect threat conditioning studies and review relevant research and suggest solutions and recommendations that flow from the HiTOP perspective. Our hope is that this effort serves as both an inflection point and practical primer for HiTOP-aligned threat conditioning research that benefits both fields. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Several leading therapies for anxiety-related disorders rely on the principles of extinction learning. However, despite decades of development and research, many of these treatments remain only moderately effective. Developing techniques to improve extinction learning is an important step towards developing improved and mechanistically-informed exposure-based therapies. In this review, we highlight human research on strategies that might augment extinction learning through reward neurocircuitry and dopaminergic pathways, with an emphasis on counterconditioning and other behaviorally-augmented forms of extinction learning (e.g., novelty-facilitated extinction, positive affect training). We also highlight emerging pharmacological and non-pharmacological methods of augmenting extinction, including L-DOPA and aerobic exercise. Finally, we discuss future directions for augmented extinction learning and memory research, including the need for more work examining the influence of individual differences and psychopathology., 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 © 2024 Elsevier Inc. All rights reserved.)

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48. Descriptive statistics and a generalized linear model were used to assess the association between selected demographic factors, self-report of daily medication adherence and plasma drug concentrations consistent with daily adherence. Among 718 paired observations from 370 participants, 43% (306/718) reported daily adherence by CASI, 65% (467/718) had drug concentrations consistent with daily adherence and 11% (81/718) had CASI responses that reported daily adherence despite having drug concentrations consistent with less-than-daily adherence. In adjusted analyses, participants who were assigned male at birth (aOR 1.42 [95% CI 1.02, 1.97]), older (5-year increments aOR 1.10 [95% CI 1.09, 1.11]), White (aOR 2.2 [95% CI 1.88, 2.56]), had advanced education (aOR 3.89 [95% CI 2.97, 5.09]), were employed (aOR 1.89 [95% CI 1.50, 2.40]), or partnered/married (aOR 2 [95% CI 1.72, 2.32]) were more likely to have drug concentrations consistent with daily adherence. Participants who were not employed (aOR 2.7 [95% CI 1.31, 5.55]) or who were single/not partnered (aOR 2.33 [CI 95% 1.25, 4.34]) were more likely to have drug concentrations that did not reflect daily adherence despite self-reported PrEP adherence. These findings support the need for ongoing adherence counseling in clinical trials of new PrEP regimens., (© 2024. The Author(s).)

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity ( P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output. NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

Abstract: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo. Here, we describe the incorporation of T-cell activation and costimulatory signals onto the surface of VivoVec particles (VVPs) in the form of a multidomain fusion protein and show enhanced in vivo transduction and improved CAR T-cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into nonhuman primates resulted in the robust generation of anti-CD20 CAR T cells and the complete depletion of B cells for >10 weeks. These data validate the VivoVec platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

While emerging research is highlighting the significant effects of culture on marital and family relationships, studies investigating relationship intimacy and abuse in non-Western cultures are non-existent. This investigation assessed relationship intimacy in Pakistani women experiencing trauma symptoms (PTSD) from domestic abuse (DA) who received a culturally informed trauma intervention in a context that differs greatly in values and assumptions about marital relationships relative to Western traditions. Forty women meeting inclusion criteria were assessed on domestic violence type and characteristics (both victim and perpetrator characteristics), PTSD symptomology, and three aspects of relationship intimacy: engagement, communication, and shared friendships. PTSD symptomology and relationship intimacy were reassessed post-intervention. Results indicated significant changes in engagement and communication intimacy following the intervention, with engagement decreasing and communication increasing. The third aspect of intimacy, namely, shared friendships, showed no change. Engagement and overall intimacy showed significant negative correlations with physical abuse, though not with sexual or psychological/emotional abuse. These findings are interpreted within a cultural context where women have few options for leaving an abusive relationship. As such, the results highlight the importance of culture when studying facets of intimate relationships and the need to use culturally informed assessments to better understand the experience of intimacy within abusive relationships., Competing Interests: The authors declare no conflicts of interest.

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experienced in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic knowledge structures (e.g., categories) is unknown. We used a modified aversive sensory preconditioning paradigm in fMRI (n = 35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24 h in the hippocampus and perirhinal cortex. Reactivation of the semantic category during threat conditioning, combined with activation of the hippocampus or medial prefrontal cortex, was predictive of subsequent amygdala reactivity toward novel category members at test. This provides evidence for online integration of emotional experiences into semantic categories, which then promotes threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying semantic structures built up over time and stored in memory as conceptual knowledge., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Efforts to identify risk and resilience factors for anxiety severity and course during the COVID-19 pandemic have focused primarily on demographic rather than psychological variables. Intolerance of uncertainty (IU), a transdiagnostic risk factor for anxiety, may be a particularly relevant vulnerability factor., Method: N = 641 adults with pre-pandemic anxiety data reported their anxiety, IU, and other pandemic and mental health-related variables at least once and up to four times during the COVID-19 pandemic, with assessments beginning in May 2020 through March 2021., Results: In preregistered analyses using latent growth models, higher IU at the first pandemic timepoint predicted more severe anxiety, but also a sharper decline in anxiety, across timepoints. This finding was robust to the addition of pre-pandemic anxiety and demographic predictors as covariates (in the full sample) as well as pre-pandemic depression severity (in participants for whom pre-pandemic depression data were available). Younger age, lower self/parent education, and self-reported history of COVID-19 illness at the first pandemic timepoint predicted more severe anxiety across timepoints with strong model fit, but did not predict anxiety trajectory., Conclusions: IU prospectively predicted more severe anxiety but a sharper decrease in anxiety over time during the pandemic, including after adjustment for covariates. IU therefore appears to have unique and specific predictive utility with respect to anxiety in the context of the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest Lauren S. Hallion and Gordon J. G. Asmundson are Associate Editor and Editor-in-Chief at Journal of Anxiety Disorders, respectively, and receive financial support through payments for their editorial work on the journal. Neither author was involved in the review of the manuscript or the decision regarding its acceptance. We have no additional conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Research on creative problem-solving finds that solutions achieved via spontaneous insight (i.e., Aha! moment) are better remembered than solutions reached without this sense of epiphany, referred to as an "insight memory advantage." We hypothesized that the insight memory advantage can spread to incidental information encoded in the moments surrounding insight as well. Participants (N = 291) were first given Rebus puzzles. After they indicated that they had found a solution, but before they could submit this solution, they were presented with scholastic facts that were incidental and unrelated to the problem at hand. Participants indicated whether they reached the solution via either insight or a step-by-step analysis. Memory results showed better performance for incidental scholastic facts presented when problem solving was accompanied by a spontaneous (Aha! experience) and induced (D'oh! experience) insight compared with solutions reached with analysis. This finding suggests that the memory advantage for problems solved via insight spreads to other unrelated information encoded in close temporal proximity and has implications for novel techniques to enhance learning in educational settings., (© 2024. The Psychonomic Society, Inc.)

Background: Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network-targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory., Methods: Continuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final n  = 25)., Results: Main analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: β = 0.10, 95% CI, 0.04 to 0.17, p  = .001; risk ratings: β = 0.07, 95% CI, 0.00 to 0.13, p  = .037)., Conclusions: Overgeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.

The thalamus is a centrally located and heterogeneous brain structure that plays a critical role in various sensory, motor, and cognitive processes. However, visualizing the individual subnuclei of the thalamus using conventional MRI techniques is challenging. This difficulty has posed obstacles in targeting specific subnuclei for clinical interventions such as deep brain stimulation (DBS). In this paper, we present DiMANI, a novel method for directly visualizing the thalamic subnuclei using diffusion MRI (dMRI). The DiMANI contrast is computed by averaging, voxelwise, diffusion-weighted volumes enabling the direct distinction of thalamic subnuclei in individuals. We evaluated the reproducibility of DiMANI through multiple approaches. First, we utilized a unique dataset comprising 8 scans of a single participant collected over a 3-year period. Secondly, we quantitatively assessed manual segmentations of thalamic subnuclei for both intra-rater and inter-rater reliability. Thirdly, we qualitatively correlated DiMANI imaging data from several patients with Essential Tremor with the localization of implanted DBS electrodes and clinical observations. Lastly, we demonstrated that DiMANI can provide similar features at 3T and 7T MRI, using varying numbers of diffusion directions. Our results establish that DiMANI is a reproducible and clinically relevant method to directly visualize thalamic subnuclei. This has significant implications for the development of new DBS targets and the optimization of DBS therapy., Competing Interests: RP is a consultant for Surgical Information Sciences, Inc. TP has been a consultant for Surgical Information Sciences, Inc. JV has received consulting fees from Abbott, Adamas, Boston Scientific, Insightec, LivaNova, Cala Health and Medtronic. He has received research grants from Boston Scientific, Medtronic, NIH, and St Jude Medical. He is on the executive advisory board for Abbott and serves on the Scientific Advisory Board for Surgical Information Sciences. JA is a consultant for Surgical Information Sciences, Inc. NH is a co-founder of Surgical Information Sciences, Inc. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Patriat, Palnitkar, Chandrasekaran, Sretavan, Braun, Yacoub, McGovern, Aman, Cooper, Vitek and Harel.)

CRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations including single nucleotide variants (SNVs) associated with diseases. Interpretation of these data is currently limited as genotypes cannot be accurately inferred from guide RNA identity alone. scSNV-seq overcomes this limitation by coupling single-cell genotyping and transcriptomics of the same cells enabling accurate and high-throughput screening of SNVs. Analysis of variants across the JAK1 gene with scSNV-seq demonstrates the importance of determining the precise genetic perturbation and accurately classifies clinically observed missense variants into three functional categories: benign, loss of function, and separation of function., (© 2024. The Author(s).)

Background: Excessive subthalamic nucleus (STN) β-band (13-35 Hz) synchronized oscillations has garnered interest as a biomarker for characterizing disease state and developing adaptive stimulation systems for Parkinson's disease (PD)., Objectives: To report on a patient with abnormal treatment-responsive modulation in the β-band., Methods: We examined STN local field potentials from an externalized deep brain stimulation (DBS) lead while assessing PD motor signs in four conditions (OFF, MEDS, DBS, and MEDS+DBS)., Results: The patient presented here exhibited a paradoxical increase in β power following administration of levodopa and pramipexole (MEDS), but an attenuation in β power during DBS and MEDS+DBS despite clinical improvement of 50% or greater under all three therapeutic conditions., Conclusions: This case highlights the need for further study on the role of β oscillations in the pathophysiology of PD and the importance of personalized approaches to the development of β or other biomarker-based DBS closed loop algorithms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET)., Background: DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely., Methods: A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores., Results: The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R 2  = 0.458, p  = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R 2  = -0.073, p  = 0.58)., Conclusion: Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes., Competing Interests: JV was a consultant for Medtronic, Boston Scientific, Abbott, and Cala Health, and serves on the External Advisory Board for Abbott and the Scientific Advisory Board for Surgical Information Sciences. NH was a co-founder and a consultant for Surgical Information Sciences. RP and TP were consultant for Surgical Information Services. The remaining 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 Ikramuddin, Brinda, Butler, Hill, Dharnipragada, Aman, Schrock, Cooper, Palnitkar, Patriat, Harel, Vitek and Johnson.)

Recent research has proposed a relationship between rigid political ideologies and underlying 'cognitive styles'. However, there remain discrepancies in how both social and cognitive rigidity are defined and measured. Problem-solving, or the ability to generate novel ideas by exploring unusual reasoning paths and challenging rigid perspectives around us, is often used to operationalize cognitive flexibility. Thus, we hypothesized a relation between forms of social rigidity, including Socio-cognitive polarization (i.e., a factor capturing conservative political ideology, absolutism/intolerance of ambiguity, and xenophobia), bullshit receptivity (i.e., overestimating pseudo-profound statements), overclaiming (tendency to self-enhance), and cognitive rigidity (i.e., problem-solving). Our results showed differences in performance on problem-solving tasks between four latent profiles of social rigidity identified in our sample. Specifically, those low in socio-cognitive polarization, bullshit, and overclaiming (i.e., less rigid) performed the best on problem-solving. Thus, we conclude that social and cognitive rigidity may share an underlying socio-cognitive construct, wherein those who are more socially rigid are also more likely to be also cognitively rigid when processing non-social information., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators-P3 and error-related negativity (ERN)-were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex-suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined., Methods: We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery., Results: Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization., Discussion: Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses., Competing Interests: RP was a Surgical Information Sciences Inc. consultant. GM was previously consulted for Abbott. NH is a shareholder of Surgical Information Sciences. MP was listed faculty for the University of Minnesota Educational Partnership with Medtronic, Inc. and has been a consultant for Zimmer Biomet, Synerfuse, Inc., NeuroOne Medical Technologies Corp., Boston Scientific, and Surgical Information Sciences, Inc. JV served as a consultant for Medtronic, Boston Scientific, and Abbott and serves on the scientific advisory board for Surgical Information Sciences. The remaining 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 Zapata Amaya, Aman, Johnson, Wang, Patriat, Hill, MacKinnon, Cooper, Darrow, McGovern, Harel, Molnar, Park, Vitek and Escobar Sanabria.)

Given the increasing use of threat conditioning and generalization for clinical-translational research efforts, establishing test-retest reliability of these paradigms is necessary. Specifically, it is an empirical question whether the same participant evinces a similar generalization gradient of conditioned responses across two sessions with the identical contingencies and stimuli. Here, 46 human volunteers participated in an identical auditory threat acquisition and generalization protocol at two sessions separated by 1-to-2 weeks. Skin conductance responses (SCR) and trial-by-trial shock risk ratings served as primary measures. We used linear mixed effects modeling to test differential threat responses and generalization gradients, and Generalizability (G) theory coefficients as our primary formal assessment of test-retest reliability of intraindividual stability and change across time. Results showed largely invariant differential conditioning and generalization gradients across time. G coefficients indicated fair reliability for acquisition and generalization SCR. In contrast, risk rating reliabilities were mixed, and reliability was particularly low for acquisition risk ratings. Our findings generally support reliability of the threat conditioning and generalization paradigm for shorter test-retest intervals and highlight their utility for assessments of behavioral interventions in mental health research, but challenges remain and further work is needed. Threat conditioning and generalization tasks are increasingly used for translational efforts to improve behavioral interventions, and thus test-retest reliability for these tasks needs to be established. Our results support the test-retest reliability of threat conditioning and generalization over a relatively short (1-to-2 week) interval, but this depends on the measure used (physiological vs. self-report). Overall, these tasks could be appropriate for repeated testing over the course of a short-duration intervention study, but more research is needed, particularly in regard to longer-duration studies., (© 2022 Society for Psychophysiological Research.)

As extinction is a context-dependent form of learning, conditioned responses tend to return when the conditioned stimulus (CS) is encountered outside the extinction context, known as contextual renewal. Counterconditioning is a technique that may lead to a more persistent reduction of the conditioned response. However, the effects of aversive-to-appetitive counterconditioning on contextual renewal in rodent studies are mixed. Further, research in humans is sparse, particularly direct statistical comparisons between counterconditioning and standard extinction techniques within the same study. Using a causal associative learning framework (the allergist task) implemented online, we compared the effectiveness of counterconditioning to standard extinction in preventing the renewal of judgements on the allergic properties of different food items (CSs). In a between-subjects design, 328 participants first learned that particular food items (CSs) lead to an allergic reaction in a specific restaurant (context A). Next, one CS was extinguished (no allergic reaction) while another CS was counterconditioned (positive outcome) in restaurant B. Causal judgements of the allergic properties of food items occurred in either the response acquisition context (ABA group, N = 112), the response reduction context where extinction and counterconditioning had occurred (ABB group, N = 107), or a novel context (ABC group, N = 109). Results showed that counterconditioning, compared to extinction, diminished the renewal of causal judgements to the CS in a novel context (ABC group). Still, casual judgements returned for both counter-conditioned and extinguished CSs in the response acquisition context (ABA group). Counterconditioning and extinction were similarly effective at preventing recovery of causal judgements in the response reduction context (ABB group); however, only in context B did participants choose the counter-conditioned CS as less likely to cause an allergic reaction in comparison to the extinguished CS. These findings indicate scenarios in which counterconditioning is more effective than standard extinction at diminishing the return of threat associations, with implications for improving the generalization of safety learning., 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 © 2023 Elsevier Inc. All rights reserved.)

Our capacity to measure diverse aspects of human biology has developed rapidly in the past decades, but the rate at which these techniques have generated insights into the biological correlates of psychopathology has lagged far behind. The slow progress is partly due to the poor sensitivity, specificity and replicability of many findings in the literature, which have in turn been attributed to small effect sizes, small sample sizes and inadequate statistical power. A commonly proposed solution is to focus on large, consortia-sized samples. Yet it is abundantly clear that increasing sample sizes will have a limited impact unless a more fundamental issue is addressed: the precision with which target behavioral phenotypes are measured. Here, we discuss challenges, outline several ways forward and provide worked examples to demonstrate key problems and potential solutions. A precision phenotyping approach can enhance the discovery and replicability of associations between biology and psychopathology.

Dimensional models of obsessive-compulsive (OC) symptoms, as seen in obsessive-compulsive disorder (OCD), are instrumental in explaining the heterogeneity observed in this condition and for informing cutting-edge assessments. Prior structural work in this area finds that OC symptoms cross-load under both Negative Affectivity and Psychoticism traits within the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5 ) Alternative Model of Personality Disorder (AMPD). However, tests of OC symptoms in conjunction with assessments of the full AMPD structure and its 25 lower-level facets representing narrower symptom content are lacking. We applied joint exploratory factor analysis to an AMPD measure (Personality Inventory for DSM-5 ; PID-5) and OC symptom data from two separate samples (total N = 1,506) to locate OC symptoms within AMPD space. OC symptoms cross-loaded on Negative Affectivity, Psychoticism, and on the low end of Disinhibition. We also report exploratory analyses of OC symptom subscales with PID-5 variables. Results are discussed in the context OC symptoms' location in PID-5 space, implications for assessment, and placement of OCD within the Hierarchical Taxonomy of Psychopathology.

Background: Postural instability is one of the most disabling motor symptoms of Parkinson's disease (PD) given its association with falls and loss of independence. Previous studies have assessed biomechanical measures of reactive stepping in response to perturbations, showing that individuals with PD exhibit inadequate postural responses to regain balance., Research Question: Does dopamine replacement therapy normalize step length in response to balance perturbations?, Methods: In this study, we estimated reactive step length, to a postural perturbation, retrospectively from a dataset of frontal plane video using 2D motion tracking and direct linear transform methods. We compared two perturbation methods: support surface translation and shoulder pull (the clinical standard) in 14 individuals with PD and 13 without PD (on and off medication), with and without partial body weight support (BWS). The primary outcome was the length of the first step taken to regain balance after the perturbation analyzed with mixed effects ANOVA, with post hoc analysis of anteroposterior (AP) and mediolateral (ML) components., Results: PD OFF medication exhibited shorter reactive step length compared to PD ON and compared to control groups for the surface translation perturbations, but no significant difference was observed for the shoulder pull perturbations., Significance: Dopamine replacement therapy affects step length in response to perturbation more robustly for surface translations than for a pull by the shoulders., Competing Interests: Declaration of Interest There are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear., Methods: Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects., Results: The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05)., Conclusions: This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tara Palnitkar: consultant for Surgical Information Sciences; Remi Patriat: consultant for Surgical Information Sciences; Jerrold Vitek: consultant for Medtronic, Boston Scientific, Abbott, and Surgical Information Sciences; Noam Harel: consultant and a shareholder for Surgical Information Sciences; all other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This experiment tested if balance performance differed between a standardized treadmill surface perturbation task and a clinical pull test and was affected by medication or the presence of body weight support in people with Parkinson's disease (PD)., Methods: Twenty-seven individuals were tested (14 PD in both ON- and OFF-medication states). Clinical pull test and rapid forward (backward fall) translations of the support surface were applied to induce postural reactions requiring at least 1 step to restore balance. The effects of pull type (clinical vs. treadmill), partial bodyweight support (0 vs 20% body weight) and group (control, PD ON-meds and PD OFF-meds) on reactive stepping as well as practice/learning effect were examined. The number of steps taken and the first step duration were entered in linear repeated-measures mixed-effect models separately., Results: The effects of pull type, group, and bodyweight support were all significant in both metrics, as was ON- vs. OFF-medication. A significant interaction term (group x pull type) was found in the first step duration, showing that the group difference was greater in treadmill compared to the clinical pull test. A significant practice effect was also observed within and across testing sessions., Conclusions: A standardized treadmill perturbation performed slightly better than the classical pull test in distinguishing between groups, and partial weight support did not substantially degrade the test's performance to detect the balance deficits in people with PD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: To examine the role of psychological flexibility as a potential mediator in the relationship between involvement in a guided self-help intervention, Self-Help Plus, and psychological distress in a sample of South Sudanese refugee women living in northern Uganda., Method: We conducted secondary analysis of data from a cluster randomized controlled trial conducted in 2018. We used multilevel mediation modeling to explore the relationship of psychological flexibility, as measured by the Acceptance and Action Questionnaire (AAQ-II), as a mediating factor in the relationship between Self-Help Plus involvement and general psychological distress as measured by the Kessler Psychological Distress Scale-6 (K6)., Results: We found strong multilevel mediation of decreased K6 scores in the treatment group by AAQ-II scores (multilevel b = -3.28). A more pronounced mediation effect was discovered immediately post intervention (b = -1.09) compared to 3-month follow-up (b = -0.84). This is in line with the current literature that demonstrates the role of psychological flexibility as a primary mechanism of change in ACT-based interventions., Conclusions: Psychological flexibility is a contributing component in the theory of change for this ACT-based intervention. Identifying the core components of interventions allows for more effective adaptation and implementation of relevant services, especially in low-resource contexts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reported coronavirus disease 2019 (COVID-19) outcomes in persons living with HIV (PLWH) vary across cohorts. We examined clinical characteristics and outcomes of PLWH with COVID-19 compared with a matched HIV-seronegative cohort in a mid-Atlantic US healthcare system. Multivariate logistic regression was used to explore factors associated with hospitalization and death/mechanical ventilation among PLWH. Among 281 PLWH with COVID-19, the mean age was 51.5 (SD 12.74) years, 63% were male, 86% were Black, and 87% had a HIV viral load <200 copies/mL. Overall, 47% of PLWH versus 24% ( p < 0.001) of matched HIV-seronegative individuals were hospitalized. Rates of COVID-19 associated cardiovascular and thrombotic events, AKI, and infections were similar between PLWH and HIV-seronegative individuals. Overall mortality was 6% ( n = 18/281) in PLWH versus 3% ( n = 33/1124) HIV-seronegative, p < 0.0001. Among admitted patients, mortality was 14% ( n = 18/132) for PLWH and 13% ( n = 33/269) for HIV-seronegative, p = 0.75. Among PLWH, hospitalization associated with older age aOR 1.04 (95% CI 1.01, 1.06), Medicaid insurance aOR 2.61 (95% CI 1.39, 4.97) and multimorbidity aOR 2.98 (95% CI 1.72, 5.23). Death/mechanical ventilation associated with older age aOR 1.06 (95% CI 1.01, 1.11), Medicaid insurance aOR 3.6 (95% CI 1.36, 9.74), and multimorbidity aOR 4.4 (95% CI 1.55, 15.9) in adjusted analyses. PLWH were hospitalized more frequently than the HIV-seronegative group and had a higher overall mortality rate, but once hospitalized had similar mortality rates. Older age, multimorbidity and insurance status associated with more severe outcomes among PLWH suggesting the importance of targeted interventions to mitigate the effects of modifiable inequities., Competing Interests: P.K. reports research grants from Eli Lilly, G.S.K., Merck, Gilead, Regeneron, and American Gene Technologies and financial interest in Merck, Johnson & Johnson, G.S.K., Gilead, and Pfizer.

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products., Competing Interests: Potential conflicts of interest. S. E. C. reports research training funding from the National Institutes of Health (NIH) through grant number T32AI007613. R. G. reports research funding from an NIH UM1 grant for HIV clinical trials; royalty payments from Elsevier for a textbook chapter on HIV therapy; and payments for educational talks at academic and non-profit institutions. J. R. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several decades of rodent neurobiology research have identified a network of brain regions that support Pavlovian threat conditioning and extinction, focused predominately on the amygdala, hippocampus, and medial prefrontal cortex (mPFC). Surprisingly, functional magnetic resonance imaging (fMRI) studies have shown inconsistent evidence for these regions while humans undergo threat conditioning and extinction. In this review, we suggest that translational neuroimaging efforts have been hindered by reliance on traditional univariate analysis of fMRI. Whereas univariate analyses average activity across voxels in a given region, multivariate pattern analyses (MVPA) leverage the information present in spatial patterns of activity. MVPA therefore provides a more sensitive analysis tool to translate rodent neurobiology to human neuroimaging. We review human fMRI studies using MVPA that successfully bridge rodent models of amygdala, hippocampus, and mPFC function during Pavlovian learning. We also highlight clinical applications of these information-sensitive multivariate analyses. In sum, we advocate that the field should consider adopting a variety of multivariate approaches to help bridge cutting-edge research on the neuroscience of threat and anxiety., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the study of frustrated quantum magnets, it is essential to be able to control the nature and degree of site disorder during the growth process, as many measurement techniques are incapable of distinguishing between site disorder and frustration-induced spin disorder. Pyrochlore-structured spinel oxides can serve as model systems of geometrically frustrated three-dimensional quantum magnets; however, the nature of the magnetism in one well-studied spinel, ZnFe 2 O 4 , remains unclear. Here, we demonstrate simultaneous control of both stoichiometry and inversion disorder in the growth of ZnFe 2 O 4 single crystals, directly yielding a revised understanding of both the collective spin behavior and lattice symmetry. Crystals grown in the stoichiometric limit with minimal site inversion disorder contravene all the previously suggested exotic spin phases in ZnFe 2 O 4 . Furthermore, the structure is confirmed on the [Formula: see text] space group with broken inversion symmetry that induces antiferroelectricity. The effective tuning of magnetic behavior by site disorder in the presence of robust antiferroelectricity makes ZnFe 2 O 4 of special interest to multiferroic devices.

Background: Unlike the other 2 criteria for diagnosing premature ejaculation (PE), namely lack of ejaculatory control and short ejaculation latency (EL), the role of bother/distress has received only minimal consideration and investigation., Aim: The specific aim was to determine both why distress is included in the PE diagnosis and whether such inclusion is advantageous to achieving better diagnostic outcomes. To this end, the review explored the historical and theoretical underpinnings of the inclusion of "bother/ distress" in the diagnosis of PE, with reference to the larger role that distress has played in the diagnosis of mental disorders, in an attempt to understand the utility (or lack thereof) of this construct in making a PE diagnosis., Methods: We reviewed the role of bother/distress across current professional definitions for PE and then expanded this discussion to include the role of distress in other sexual dysfunctions. We then included a brief historical perspective regarding the role that distress has played in the diagnosis of PE. This discussion is followed by a deeper look at 2 nosological systems, namely DSM and ICD, to allow perspective on the inclusion of the bother/distress construct in the diagnosis of mental and behavioral disorders, including the assumptions/arguments put forward to include or exclude bother/distress as an important criterion underlying various professional assumptions., Outcome: Determination of the value and/or need of including bother/distress as a necessary criterion for the diagnosis of PE., Results: Based on the research literature, bother/distress does not appear to be as critical for a PE diagnosis as either the lack of ejaculatory control or short EL. It is the weakest of the differences among men with and without PE, and recent evidence suggests that its inclusion is generally redundant with the severity of the 2 other criteria for PE, ejaculatory control and EL., Clinical Translation: Bother/distress appears to serve little purpose in the diagnosis of PE yet its assessment may be important for the treatment strategy and for assessing treatment effectiveness., Strengths and Limitations: This review did not provide a critical analysis of the literature regarding the role of bother/distress in PE, but rather focused on its potential value in understanding and diagnosing PE., Conclusion: Although bother/distress appears to add little to the improvement of accuracy for a PE diagnosis, understanding and assessing the man's or couple's experience of distress has important implications for the treatment strategy and focus, as well as for assessing treatment success. Rowland DL, Cooper SE. The Tenuous Role of Distress in the Diagnosis of Premature Ejaculation: A Narrative Review. Sex Med 2022;10:100546., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

To elucidate the role of the basal ganglia during REM sleep movements in Parkinson's disease (PD) we recorded pallidal neural activity from four PD patients. Unlike desynchronization commonly observed during wakeful movements, beta oscillations (13-35 Hz) synchronized during REM sleep movements; furthermore, high-frequency oscillations (150-350 Hz) synchronized during movement irrespective of sleep-wake states. Our results demonstrate differential engagement of the basal ganglia during REM sleep and awake movements., (© 2022. The Author(s).)

Approaches to control basal ganglia neural activity in real-time are needed to clarify the causal role of 13-35 Hz ("beta band") oscillatory dynamics in the manifestation of Parkinson's disease (PD) motor signs. Here, we show that resonant beta oscillations evoked by electrical pulses with precise amplitude and timing can be used to predictably suppress or amplify spontaneous beta band activity in the internal segment of the globus pallidus (GPi) in the human. Using this approach, referred to as closed-loop evoked interference deep brain stimulation (eiDBS), we could suppress or amplify frequency-specific (16-22 Hz) neural activity in a PD patient. Our results highlight the utility of eiDBS to characterize the role of oscillatory dynamics in PD and other brain conditions, and to develop personalized neuromodulation systems., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R. Patriat is a consultant for Surgical Information Sciences Inc. G.F. Molnar has previously consulted for Abbott. N. Harel is a shareholder of Surgical Information Sciences. M.C. Park is listed faculty for University of Minnesota Educational Partnership with Medtronic, Inc. and has been a consultant for Zimmer Biomet, Synerfuse, Inc., NeuroOne Medical Technologies Corp., Boston Scientific, and Surgical Information Sciences, Inc. J. L. Vitek has served as a consultant for Medtronic, Boston Scientific, and Abbott and serves on the scientific advisory board for Surgical Information Sciences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Generalization of conditioned fear is adaptive in some situations but maladaptive when fear excessively generalizes to innocuous stimuli with incidental resemblance to a genuine threat cue. Recently, empirical interest in fear generalization as a transdiagnostic explanatory mechanism underlying anxiety-related disorders has accelerated. As there are now several studies of fear generalization across multiple types of anxiety-related disorders, the authors conducted a meta-analysis of studies reporting behavioral measures (subjective ratings and psychophysiological indices) of fear generalization in anxiety-related disorder vs. comparison groups. We conducted systematic searches of electronic databases (conducted from January-October 2020) for fear generalization studies involving anxiety-related disorder groups or subclinical analog groups. A total of 300 records were full-text screened and two unpublished datasets were obtained, yielding 16 studies reporting behavioral fear generalization measures. Random-effects meta-analytic models and meta-regressions were applied to the identified data. Fear generalization was significantly heightened in anxiety-related disorder participants (N = 439) relative to comparison participants (N = 428). We did not identify any significant clinical, sample, or methodological moderators. Heightened fear generalization is quantitatively supported as distinguishing anxiety-related disorder groups from comparison groups. Evidence suggests this effect is transdiagnostic, relatively robust to experimental or sample parameters, and that generalization paradigms are a well-supported framework for neurobehavioral investigations of learning and emotion in anxiety-related disorders. We discuss these findings in the context of prior fear conditioning meta-analyses, past neuroimaging investigations of fear generalization in anxiety-related disorders, and future directions and challenges for the field., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Context: The United States has witnessed a disproportionate rise in substance use disorders (SUD) and co-occurring mental health disorders, paired with housing instability, especially among racially minoritized communities. Traditional in-patient residential treatment programs for SUD have proven inconsistent in their effectiveness in preventing relapse and maintaining attrition among these patient populations. There is evidence showing that peer recovery programs led by individuals who have lived experience with SUD can increase social support and foster intrinsic motivation within participants to bolster their recovery. These peer recovery programs, when coupled with a standardized training program for peer recovery coaches, may be very efficacious at improving patient health outcomes, boosting performance on Substance Abuse and Mental Health Services Administration (SAMHSA) national outcome measures (NOMs), and helping participants build an overall better quality of life., Objectives: The goal of this study is to highlight the efficacy of a peer recovery program, the Minority Aids Initiative, in improving health outcomes and associated NOMs in men with SUD and/or co-occurring mental health disorder., Methods: Participants received six months of peer recovery coaching from trained staff. Sessions were guided by the Manual for Recovery Coaching and focused on 10 different domains of recovery . Participants and coaches set long-term goals and created weekly action plans to work toward them. Standardized assessments (SAMHSA's Government Performance and Results Act [GPRA] tool, Addiction Severity Index [ASI]) were administered by recovery coaches at intake and at the 6-month time point to evaluate participant progress. Analyses of participant recovery were carried out according to SAMHSA's six NOMs and assessed the outcomes of the intervention and their significance., Results: A total of 115 participants enrolled in the program over a 2-year period. Among them, 53 were eligible for 6-month follow-up interviews. In total, 321 sessions were held, with an average of three sessions per participant. Participants showed marked improvement across five of the six NOMs at the end of the 6-month course and across all ASI outcomes, with the exception of three in which participants reported an absence or few symptoms at intake., Conclusions: Our study shows that participants receive benefits across nearly all NOM categories when paired with recovery coaches who are well trained in medication-assisted treatment (MAT) and medications for opioid use disorder (MOUD) over a 6-month period. We see the following: a higher rate of abstinence; increased housing stability; lower health, behavioral, and social consequences; lower depression and anxiety; longer participant-recovery coach exposure time; and higher follow-up rates. We hope that our results can contribute to advancements and greater acceptance in the implementation of peer recovery coaching as well as an improvement in the lives of the communities affected by substance use., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Heightened generalization of conditioned fear and avoidance to safe stimuli resembling threat is a key feature of pathological anxiety and might contribute to the increased prevalence of anxiety-related disorders among women. Though animal studies have documented over-generalized fear in female versus male rodents, analogous work in humans is sparse, and no studies to date have examined gender differences in generalized avoidance. We addressed this gap by testing 170 self-identified women (n = 85) and men (n = 85) using a video game-based task assessing generalized Pavlovian fear (perceived threat, fear-potentiated startle) and generalized instrumental avoidance. Instrumental measures of generalization reflected maladaptive avoidance by virtue of being unnecessary to secure safety and incurring a cost of losing the game in which the task is embedded. Women displayed increases in both Pavlovian generalization of perceived threat and maladaptive generalized avoidance. Additionally, decreased motivation to win the game among women mediated the effect of gender on generalized avoidance, and generalized perceived risk and tendencies toward experiential avoidance positively predicted generalized avoidance in women but not men. Overall, findings implicate the undue spread of fear and avoidance to safe stimuli resembling danger among women as a candidate mechanism for differential rates of clinical anxiety across the genders., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Treadmills provide a safe and convenient way to study the gait of people with Parkinson's disease (PD), but outcome measures derived from treadmill gait may differ from overground walking., Objective: To investigate how the relationships between gait metrics and walking speed vary between overground and treadmill walking in people with PD and healthy controls., Methods: We compared 29 healthy controls to 27 people with PD in the OFF-medication state. Subjects first walked overground on an instrumented gait walkway, then on an instrumented treadmill at 85%, 100% and 115% of their overground walking speed. Average stride length and cadence were computed for each subject in both overground and treadmill walking., Results: Stride length and cadence both differed between overground and treadmill walking. Regressions of stride length and cadence on gait speed showed a log-log relationship for both overground and treadmill gait in both PD and control groups. The difference between the PD and control groups during overground gait was maintained for treadmill gait, not only when treadmill speed matched overground speed, but also with ± 15% variation in treadmill speed from that value., Significance: These results show that the impact of PD on stride length and cadence and their relationship to gait speed is preserved in treadmill as compared to overground walking. We conclude that a treadmill protocol is suitable for laboratory use in studies of PD gait therapeutics., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A "stepping stone" task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12-30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation., Competing Interests: Conflict of Interest: 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.

Overgeneralization of conditioned fear to safe stimuli that resemble a previously-learned threat-cue is a well-studied correlate of clinical anxiety, yet whether conditioned disgust generalizes remains unknown, as does the extent to which such generalization is associated with disgust-related traits and maladaptive outcomes. The present study addresses this gap by adapting a validated fear-generalization paradigm to assess conditioned disgust and behavioral avoidance to a disgust-cue (CS+) paired with a disgusting video clip, and safe generalization stimuli parametrically varying in perceptual similarity to CS+. For comparison, levels of fear generalization were also assessed using the original fear-generalization paradigm. In both paradigms, costly and unnecessary avoidance to safe threat-cue approximations analogues maladaptive outcomes of generalization. In the disgust paradigm only, disgust-proneness was associated with elevated perceived risk to safe stimuli and increases in the extent to which such elevations were accompanied by maladaptive avoidance. Comparable levels of generalization, and positive associations between generalization and maladaptive avoidance, were found across disgust and fear paradigms. Results confirm that conditioned disgust is subject to generalization, implicate generalized disgust as a source of maladaptive avoidance particularly among those prone to disgust, and suggest a potential role for these processes in the etiology and maintenance of disgust-related disorders., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Sexual minority (SM) tobacco users are less likely to successfully quit than heterosexuals, yet little evidence describes cessation behaviors in this population over time., Aims and Methods: Our study investigated quit motivations, attempts, and methods in a longitudinal cohort of adult tobacco users by sexual orientation. Participants (N = 1177) completed interviews every 6 months through 48 months and reported quit attempts (24-hour tobacco free), successful quits (7-day point prevalence abstinence), motivations, and methods. Chi-squared and Fisher's exact tests assessed differences by heterosexual and SM orientation, gender, and quit outcome (attempt-only vs. successful quit)., Results: Quit rates were similar for heterosexual and SM adults. Over half attempted to quit at least once over 48 months, but few remained abstinent (SM: 16.9%; heterosexual: 12.1%). Most used nicotine replacement therapy (SM: 31.9%; heterosexual: 26.1%) or tobacco product substitution (SM: 27.7%; heterosexual: 21.2%). Few used quitlines (SM: 4.3%; heterosexual: 1.3%) or Internet-based programs (SM: 6.4%; heterosexual: 1.3%). Quit motivations included health concerns, family, and physical fitness. Participants reporting a successful quit were more likely to report a household member quit smoking than 24-hour quit attempters. Among participants reporting a successful quit, more SM than heterosexual participants reported that a coworker quit smoking (55.6% vs. 33.1%, p = .009)., Conclusions: We found few differences between heterosexual and SM tobacco users in our sample. Many repeatedly attempt to quit, yet few used evidence-based methods. Leveraging online quit programs, health messages, and family members in tailored cessation interventions may help SM and heterosexual tobacco users successfully quit., Implications: SM and heterosexual tobacco users evidenced few differences in quit behaviors. Over 4 years, a majority attempted to quit, with over a third making repeated quit attempts. Nicotine replacement therapy and tobacco product substitution were mostly used during quit attempts; however, more SM than heterosexual men reported using web-based quit programs. Personal health and family concerns were universal motivations to quit, yet SM women also cited physical fitness as a primary motivation. Tobacco users reporting that a household member stopped smoking were more likely to successfully quit. More SM than heterosexual men reported that a coworker quit smoking., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Laboratory experiments using fear conditioning and extinction protocols help lay the groundwork for designing, testing, and optimizing innovative treatments for anxiety-related disorders. Yet, there is limited basic research on fear conditioning and extinction in obsessive-compulsive disorder (OCD). This is surprising because exposure-based treatments based on associative learning principles are among the most popular and effective treatment options for OCD. Here, we systematically review and critically assess existing aversive conditioning and extinction studies of OCD. Across 12 studies, there was moderate evidence that OCD is associated with abnormal acquisition of conditioned responses that differ from comparison groups. There was relatively stronger evidence of OCD's association with impaired extinction processes. This included multiple studies finding elevated conditioned responses during extinction learning and poorer threat/safety discrimination during recall, although a minority of studies yielded results inconsistent with this conclusion. Overall, the conditioning model holds value for OCD research, but more work is necessary to clarify emerging patterns of results and increase clinical translational utility to the level seen in other anxiety-related disorders. We detail limitations in the literature and suggest next steps, including modeling OCD with more complex conditioning methodology (e.g., semantic/conceptual generalization, avoidance) and improving individual-differences assessment with dimensional techniques., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Strategies for addressing anxiety-related decrements in performance have been implemented across a variety of domains, including Sex, Sport, and Stage. In this review, we (1) iterate the dominant anxiety-related remediation strategies within each of these domains; (2) identify over-lapping and domain-specific strategies; and (3) attempt to unify the conceptualization of performance-related anxiety across these three areas under the information-processing framework of the Reflective/deliberative-Impulsive/automatic Model (RIM). Despite both diversity and similarity in remediation approaches across domains, we found that many strategies appear to share the common goal of maintaining a dominant automatic style of information processing in high performance demand situations. We then describe how various remediation strategies might hypothetically fit within the RIM framework and its subcomponents, identifying each intervention as falling into one or more broad categories related to achieving and/or maintaining dominance in automatic information processing. We conclude by affirming the benefit of adopting a unifying information-processing framework for the conceptualization of performance-related anxiety, as a way of both guiding future cross- and inter- disciplinary research and elucidating effective remediation models that share common pathways/mechanisms to improved performance.

People diagnosed with schizophrenia have been broadly observed to experience deficits in clinical and cognitive insight; however, less is understood about how these deficits are related. One possibility is that these deficits co-occur among people when other deficits in cognition are present, such as in executive function, social cognition, and metacognition, which may either promote the development of both forms of poor insight or allow one to negatively influence the other. To explore this possibility, we conducted a cluster analysis using assessments of clinical and cognitive insight among 95 adults with a schizophrenia spectrum disorder. As predicted, this analysis yielded a group with concurrently poor clinical and cognitive insight ( n = 36). Additional groups were found with concurrently good clinical and cognitive insight ( n = 28) and poor clinical insight and good cognitive insight ( n = 31). Groups were then compared on assessments of executive function, social cognition, and metacognition. The group with concurrently lower levels of cognitive and clinical insight had significantly poorer metacognition relative to the other groups. In particular, they tended to form more fragmented and less integrated ideas about themselves and others. No differences were found for executive function or social cognition. The result may suggest that while clinical and cognitive insight is partially orthogonal phenomena, relatively lower levels of metacognition, or difficulties forming integrated ideas about oneself and others, maybe a condition leading to the confluence of lower clinical and cognitive insight. Interventions targeting metacognition may be of particular use for this group., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)