Analysis of post-market adverse events of istradefylline: a real-world study base on FAERS database.

Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

Pollen nutrition structures bee and plant community interactions.

As bees' main source of protein and lipids, pollen is critical for their development, reproduction, and health. Plant species vary considerably in the macronutrient content of their pollen, and research in bee model systems has established that this variation both modulates performance and guides floral choice. Yet, how variation in pollen chemistry shapes interactions between plants and bees in natural communities is an open question, essential for both understanding the nutritional dynamics of plant-pollinator mutualisms and informing their conservation. To fill this gap, we asked how pollen nutrition (relative protein and lipid content) sampled from 109 co-flowering plant species structured visitation patterns observed among 75 subgenera of pollen-collecting bees in the Great Basin/Eastern Sierra region (USA). We found that the degree of similarity in co-flowering plant species' pollen nutrition predicted similarity among their visitor communities, even after accounting for floral morphology and phylogeny. Consideration of pollen nutrition also shed light on the structure of this interaction network: Bee subgenera and plant genera were arranged into distinct, interconnected groups, delineated by differences in pollen macronutrient values, revealing potential nutritional niches. Importantly, variation in pollen nutrition alone (high in protein, high in lipid, or balanced) did not predict the diversity of bee visitors, indicating that plant species offering complementary pollen nutrition may be equally valuable in supporting bee diversity. Nutritional diversity should thus be a key consideration when selecting plants for habitat restoration, and a nutritionally explicit perspective is needed when considering reward systems involved in the community ecology of pollination.

Roadmap for embedding health equity research into learning health systems.

BACKGROUND: Achieving health equity is vital to fulfil the quadruple aim for optimal healthcare system performance. Traditionally, academic medicine and healthcare systems have focused their efforts on addressing health inequities with an emphasis on improving workforce diversity. Although this approach is an important requisite, a diverse workforce alone is not sufficient; rather holistic health equity should be established as the anchoring principal mission of all academic medical centres, residing at the intersection of clinical care, education, research and community. METHODS: NYU Langone Health (NYULH) has embarked on significant institutional changes to position itself as an equity-focused learning health system. One-way NYULH accomplishes this is through the establishment of a health equity research roadmap, which serves as the organising framework through which we conduct embedded pragmatic research in our healthcare delivery system to target and eliminate health inequities across our tripartite mission of patient care, medical education and research. RESULTS: This article outlines each of the six elements of the NYULH roadmap. These elements include: (1) developing processes for collecting accurate disaggregate data on race, ethnicity and language, sexual orientation and gender identity and disability; (2) using a data-driven approach to identify health equity gaps; (3) creating performance and metric-based quality improvement goals to measure progress toward elimination of health equity gaps; (4) investigating the root cause of the identified health equity gap; (5) developing and evaluating evidence-based solutions to address and resolve the inequities; and (6) continuous monitoring and feedback for system improvements. CONCLUSION: Application of each element of the roadmap can provide a model for how academic medical centres can use pragmatic research to embed a culture of health equity into their health system.

Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

Combining cannabis and melatonin treatment with a rehabilitation program improved symptoms in a dog with compulsive disorder: A case report.

Compulsive disorder in dogs (CD) is characterized by constant and time-consuming repetition of behaviors, emancipated from the environment, that definitely compromise their everyday life activities. Here, we documented the efficacy of a novel approach to counteract the negative symptoms of CD in a 5-year-old mongrel dog, previously found to be resistant to the conventional antidepressant. The patient underwent an integrated and interdisciplinary approach, based on the cannabis and melatonin co-administration, together with a tailored 5-month-lasting behavioral program. Observational findings showed a lower rate of compulsive episodes and better management of the dog as well, when compared to the previous paroxetine treatment. We followed him for an additional four months of therapy, and the owners reported easier management of the dog, as reduction of abnormal behaviors to a level acceptable to the owners. Overall, our data so far collected in the CD dog may allow us to test more deeply the feasibility and safety of such an off-label approach, at both preclinical and clinical levels.

Efficacy of cognitive-behavioral therapy in improving the quality of life of people with compulsive gambling, a systematic review.

FUNDAMENTALS: Cognitive-behavioral therapy can reduce gambling behavior and other symptoms of pathological gambling. AIM: To synthesize and analyze the evidence on the efficacy of cognitive-behavioral interventions to improve the quality of life of people with pathological gambling. METHODOLOGY: Systematic review with a narrative synthesis of clinical trials published in English and Spanish in Medline, Scopus, Web of Science, CINAHL, The Cochrane Library Plus, PsycoInfo, and ProQuest of articles until January 2020 that will analyze this phenomenon. The PRISMA Declaration was followed and the quality of the articles was analyzed with the Jadad scale. RESULTS: 1233 articles were found, including nine in the review. Two studies confirmed the efficacy of cognitive behavioral therapy-based interventions for improving the quality of life in people with pathological gambling. In addition, these interventions improved depression, anxiety, the amount of money played, and reduced alcohol consumption and the gambling diagnosis score, which had an impact on improving the quality of life. Cognitive behavioral interventions were more effective when it was supported by a manual or when were combined with Mindfulness or Player Anonymous sessions. Having better long-term results in these cases. CONCLUSIONS: Cognitive behavioral-based interventions can improve the quality of life of people with pathological gambling and other psychological variables without being its immediate effect. Future research should analyze whether they are more efficacy online or in person, individually, or in groups, and the number of sessions required for their effects to last over time.

Perspective: Can psychedelic-assisted therapy be a promising aid in compulsive sexual behavior disorder treatment?

Recently, there has been an increase in studies yielding evidence for psychedelics' anxiolytic and anti-depressive qualities. Preliminary evidence for treatment in substance addiction is also available. In our manuscript, we present a perspective on the possible effectiveness and mechanisms of action of psychedelics' introduction in the treatment of Compulsive Sexual Behavior Disorder (CSBD) and other p roblematic sexual behaviors, which are considered representative of the so-called "behavioral addiction" category. Evidence for the efficacy of Mindfulness Based Interventions in CSBD treatment is promising. Psychedelics- and mindfulness-induced states share common characteristics on both a subjective and objective level. One of the proposed mechanisms regards reduction of experiential avoidance through the promotion of exposure and acceptance. On the neurophysiological level, a shift from higher- to lower-level association regions and an impact on 5- HT2A receptors is observed. Elaborated mechanisms explain the possible enhancement of therapeutic processes by psychedelics. Psychedelics' relative safety and low addictive potential support their introduction into traditional forms of therapy for CSBD and other out of control behaviors.

Effects of the psychoactive compounds in green tea on risky decision-making.

Epigallocatechin-3-gallate (EGCG) and caffeine are the two primary compounds found in green tea. While EGCG has anxiolytic and anti-inflammatory effects, its acute effects on cognition are not well understood. Furthermore, despite widespread green tea consumption, little is known about how EGCG and caffeine co-administration impacts behavior. Here, we investigated the effects of multiple doses of either EGCG or caffeine on a rat model of risk-taking. This was assessed using the risky decision-making task (RDT), in which rats choose between a small, well-tolerated reward and a large reward with escalating risk of mild footshock. Rats were tested in RDT after acute systemic administration of EGCG, caffeine or joint EGCG and caffeine. EGCG caused a dose-dependent reduction in risk-taking without affecting reward discrimination or task engagement. Caffeine did not impact risk-taking, but elevated locomotor activity and reduced task engagement at high doses. Finally, exposure to both EGCG and caffeine had no effect on risk-taking, suggesting that low-dose caffeine is sufficient to mask the risk-aversion caused by EGCG. These data suggest EGCG as a potential therapeutic treatment for psychological disorders that induce compulsive risky decision-making.

Compulsive sexual behavior, religiosity, and spirituality: A systematic review.

BACKGROUND AND AIMS: In recent years, increasing attention has been given to the relationship between compulsive sexual behavior (CSB), religiosity, and spirituality. This review summarizes research examining the relationship CSB has with religiosity and spirituality, clarifying how these constructs inform the assessment and treatment of this syndrome. METHODS: The present paper reviews research published through August 1, 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Only studies providing quantitative analyses were included. RESULTS: This review identified 46 articles, subsuming 59 studies, analyzing the relationship between CSB and religiosity or spirituality. Most studies used cross-sectional designs with samples primarily composed of heterosexual White men and women. Generally, the studies found small to moderate positive relationships between religiosity and CSB. Studies considering the mediating or moderating role of moral incongruence identified stronger, indirect relationships between religiosity and problematic pornography use (PPU), a manifestation of CSB. Few studies examined the association between spirituality and CSB, but those that did either reported negative relationships between indicators of spiritual well-being and CSB or positive relationships between CSB and aspects of spiritual struggles. DISCUSSION AND CONCLUSIONS: Although research examining CSB and religiosity has flourished, such growth is hampered by cross-sectional samples lacking in diversity. Moral incongruence assists in explaining the relationship between religiosity and PPU, but future research should consider other manifestations of CSB beyond PPU. Attention should also be given to examining other religiosity and spirituality constructs and obtaining more diverse samples in research on CSB, religiosity, and spirituality.

Input-selective adenosine A1 receptor-mediated synaptic depression of excitatory transmission in dorsal striatum.

The medial (DMS) and lateral (DLS) dorsal striatum differentially drive goal-directed and habitual/compulsive behaviors, respectively, and are implicated in a variety of neuropsychiatric disorders. These subregions receive distinct inputs from cortical and thalamic regions which uniquely determine dorsal striatal activity and function. Adenosine A1 receptors (A1Rs) are prolific within striatum and regulate excitatory glutamate transmission. Thus, A1Rs may have regionally-specific effects on neuroadaptive processes which may ultimately influence striatally-mediated behaviors. The occurrence of A1R-driven plasticity at specific excitatory inputs to dorsal striatum is currently unknown. To better understand how A1Rs may influence these behaviors, we first sought to understand how A1Rs modulate these distinct inputs. We evaluated A1R-mediated inhibition of cortico- and thalamostriatal transmission using in vitro whole-cell, patch clamp slice electrophysiology recordings in medium spiny neurons from both the DLS and DMS of C57BL/6J mice in conjunction with optogenetic approaches. In addition, conditional A1R KO mice lacking A1Rs at specific striatal inputs to DMS and DLS were generated to directly determine the role of these presynaptic A1Rs on the measured electrophysiological responses. Activation of presynaptic A1Rs produced significant and prolonged synaptic depression (A1R-SD) of excitatory transmission in the both the DLS and DMS of male and female animals. Our findings indicate that A1R-SD at corticostriatal and thalamostriatal inputs to DLS can be additive and that A1R-SD in DMS occurs primarily at thalamostriatal inputs. These findings advance the field's understanding of the functional roles of A1Rs in striatum and implicate their potential contribution to neuropsychiatric diseases.

High-frequency neuromodulation improves obsessive-compulsive behavior.

Nearly one billion people worldwide suffer from obsessive-compulsive behaviors1,2, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive-compulsive behaviors as maladaptive habit learning3,4, which may be associated with abnormal beta-gamma neurophysiology of the orbitofrontal-striatal circuitry during reward processing5,6. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta-gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive-compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive-compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive-compulsive behavior, suggest a unifying functional role of rhythms in the beta-gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.

A pilot study of mindfulness-based relapse prevention for compulsive sexual behaviour disorder.

BACKGROUND AND AIMS: Compulsive sexual behaviour disorder (CSBD) is a medical condition that can impair social and occupational functioning and lead to severe distress. To date, treatment effectiveness studies of CSBD are under-developed; typically, treatment for CSBD is based on guidelines for substance or other behavioural addictions. Mindfulness-based relapse prevention (MBRP) is an evidence-based treatment for substance addiction aimed at, among other things, reducing craving and negative affect-i.e. processes that are implicated in the maintenance of problematic sexual behaviours. However, to our knowledge no prior research has been published evaluating mindfulness-based intervention (MBI) in the treatment of CSBD, except two clinical case reports. Therefore, the aim of the current pilot study was to examine whether MBRP can lead to clinical improvement in CSBD. Methods: Participants were 13 adult males with a diagnosis of CSBD. Before and after the eight-week MBRP intervention, participants completed a booklet of questionnaires including measurements of porn viewing, masturbation and emotional distress. Results: As expected, we found that after MBRP participants spent significantly less time engaging in problematic pornography use and exhibited a decrease in anxiety, depression and obsessive-compulsive (OC) symptoms. Discussion and Conclusions: The findings indicate that MBRP could be beneficial for CSBD individuals. Further clinical effectiveness studies with bigger sample sizes, delayed post-training measurements and randomised control trial design are warranted. In conclusion, MBRP leads to a decrease in time spent watching porn and a decrease in emotional distress in CSBD patients.

But first, coffee: The roles of arousal and inhibition in the resistance of compulsive cleansing in individuals with high contamination fears.

Inhibition plays a crucial role in reducing intrusive thoughts and compulsive behaviors, such as handwashing, in response to the feeling of disgust. The current study examines whether manipulating arousal can facilitate inhibition and the resistance of compulsive cleansing. Forty-seven participants with high contamination fears were recruited for this study. Participants were divided into a caffeine group or a no-caffeine group. Participants touched a potentially contaminated and disgusting stimulus ("dirty" diapers) and were asked to wait as long as they could before washing their hands. Only the caffeine group exhibited greater pre-post stop-signal reaction time improvement in the stop-signal task, indicating improved inhibition. Participants in the caffeine group exhibited significantly lower subjective distress and urges-to-wash their hands both after touching the stimulus and while waiting to engage in the cleansing behavior. Similarly, the caffeine group resisted the urge to compulsively cleanse for about twice as long as those in the no-caffeine group. Time spent washing, subjective distress levels, and urge-to-wash levels after participants washed their hands were similar between groups. The current findings support the notion that increased arousal improves inhibition, which may play a role in improving our ability to resist intrusive disgust and compulsive cleansing behaviors.

Chest Wall Mobility: Identification of Underlying Predictors.

OBJECTIVE: The purpose of this study was to identify factors contributing to normal mobility or hypermobility of the chest wall. METHODS: Seventy-eight young adults were divided into 2 groups: patients with normal mobility (group 1, n = 40) and hypermobility of the chest wall (group 2, n = 38). The mean mobility of the chest wall in groups 1 and 2 was 9.9 and 6.1 cm, respectively. The mean age of groups 1 and 2 was 22.2 and 21.5 years, respectively. The Brief Symptom Inventory, State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale were used to evaluate the psychometric properties. Quality of life was assessed using 12-Item Short Form Health Survey. Smoking status was determined via self-report of current smoking status. Chest wall mobility was measured using thoracic and axillary cirtometry. Pulmonary functions were evaluated using a Spirobank II device. Subsequently, forced vital capacity (FVC), forced expiratory volume in 1 second, peak expiratory flow, and forced expiratory flow 25% to 75% were verified. Carefusion Micro RPM and the 6-minute walk test were used to evaluate maximal respiratory pressures and functional capacity, respectively. RESULTS: With backward linear regression models, FVC and obsessive-compulsive traits were significant predictors of chest wall mobility (R²â€¯= 0.27; P < .001 and P = .01, respectively). In logistic regression models, FVC, maximum inspiratory pressure, and obsessive-compulsive traits were significant predictors of normal mobility/hypermobility of the chest wall (R²â€¯= 0.42; P < .001, P = .01, and P = .03, respectively). CONCLUSION: Forced vital capacity, maximum inspiratory pressure, and obsessive-compulsive traits are significant predictors of chest wall mobility and normal mobility or hypermobility of the chest wall.

Imaginal architectural devices and the ritual space of medieval necromancy.

The material and spatial dimensions documented in the manuscripts of ritual magic that circulated in the medieval and early modern periods have long eluded researchers. Studying where those rituals take place is important to understand the history of the practice of ritual magic. Few attempts have been done to interpret the reasons behind the construction of magic circles and the use of domestic locations. The author introduces a new interpretative category of such ritual spaces: imaginal architectural devices (IADs). IADs pick out a specific kind of portable, spatially unfixed ritual space, where "magical" ones are a key example. They are temporary architectural artefacts, attested across a swath of sources of ritual magic, that work as strategic tools for orienting cognition, behavior, and belief. Drawing on spatial theory and cognitive studies, the author constructs IADs as a typological category for comparative analysis. It describes architectural operations that work at the interplay between mental projections and material culture, and that modify the perception of space. In the second part of the article, IADs will be applied to study the circles described in the second section of the Liber Iuratus Honorii, a thirteenth-century handbook containing instructions on how to conjure different ranks of spirits. In the end, the author suggests future directions of research on the transmission of IADs into contemporary ritual magic.

Reducing compulsive Internet use and anxiety symptoms via two brief interventions: A comparison between mindfulness and gradual muscle relaxation.

BACKGROUND: Compulsive Internet use (CIU) refers to those individuals who experience a loss of control regarding their online use. Although suffered by a minority, a much larger proportion of adults report to be experiencing early signs of CIU, which can become more problematic if sustained over time, especially when used as a coping mechanism for stress. Since compulsive behaviors are characterized by executing behaviors on "automatic pilot," mindfulness techniques, which help individuals relate more consciously with their environment, could help develop a more adaptive relationship with technology. However, mindfulness interventions are often lengthy hence not ideal for busy individuals with early signs of CIU. AIMS: This study tested the effectiveness of a brief mindfulness intervention (10 min a day for 2 weeks) to reduce CIU and anxiety and depression symptoms, in relation to an equivalent length classic arousal descending technique (i.e., gradual-muscle-relaxation), and a wait-list control group. METHODS: A randomized controlled trial (RCT) was used with assessments at pre- and post-phases. Participants showing initial signs of CIU were allocated to a mindfulness-group (n = 343), gradual-relaxation (n = 301), or a wait-list control group (n = 350). RESULTS: The mindfulness and gradual-muscle-relaxation participants were equally effective in reducing anxiety and depression. The mindfulness intervention was more effective reducing CIU symptoms. DISCUSSION: Given the large sample sizes of this RCT, these results are promising, although follow-up studies are needed. Considering health hazards of the "always-on-culture" and the popularity of bite-sized learning, the effectiveness of easy-to fit-in daily life health practices is a positive development.

Mindfulness predicts insight in obsessive-compulsive disorder over and above OC symptoms: An experience-sampling study.

Insight in obsessive-compulsive disorder (OCD) is assumed to fluctuate over time. However, temporal variations of insight and its correlates in OCD have never been empirically studied. We used ecological momentary assessment (EMA) to analyze the temporal variation of insight into the unreasonableness of the threat-related core belief (1), into the senselessness of compulsions to prevent this belief from occurring (2), and into the belief, itself, as being due to OCD (3). Furthermore, we analyzed whether worry, self-punishment and mindfulness are associated with these aspects of insight. A total of 50 OCD patients underwent EMA 10 times a day over 6 consecutive days. Data were analyzed using multilevel modelling. Results revealed that multiple time-points within individuals accounted for up to 51.4% of insight variance, indicating a substantial fluctuation of insight over time. Root mean square successive difference (rMSSD) scores indicated significantly higher fluctuation patterns in the doubt/checking dimension as compared to taboo thoughts throughout all aspects of insight. As hypothesized, self-punishment and mindfulness significantly predicted insight into the unreasonableness of the threat-related belief and the senselessness of compulsions to prevent this belief from occurring. Mindfulness demonstrated the greatest predictive value and remained significant after controlling for OC symptoms. Contrary to expectation, worry, as it was measured in our study, was not associated with insight. Besides providing evidence for insight fluctuation, our results indicate that mindfulness-based strategies might be beneficial for increasing insight in OCD.

Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

Binge eating (BE) is a heritable trait associated with eating disorders and involves episodes of rapid, large amounts of food consumption. We previously identified cytoplasmic FMR1-interacting protein 2 (Cyfip2) as a genetic factor underlying compulsive-like BE in mice. CYFIP2 is a homolog of CYFIP1 which is one of four paternally-deleted genes in patients with Type I Prader-Willi Syndrome (PWS), a neurodevelopmental disorder whereby 70% of cases involve paternal 15q11-q13 deletion. PWS symptoms include hyperphagia, obesity (if untreated), cognitive deficits, and obsessive-compulsive behaviors. We tested whether Cyfip1 haploinsufficiency (+/-) would enhance compulsive-like behavior and palatable food (PF) intake in a parental origin- and sex-dependent manner on two Cyfip2 genetic backgrounds, including the BE-prone C57BL/6N (Cyfip2N/N) background and the BE-resistant C57BL/6J (Cyfip2J/J) background. Cyfip1+/- mice showed increased compulsive-like behavior on both backgrounds and increased PF intake on the Cyfip2N/N background. In contrast, maternal Cyfip1 haploinsufficiency on the BE-resistant Cyfip2J/J background induced a robust escalation in PF intake in wild-type Cyfip1J/J males while having no effect in Cyfip1J/- males. Notably, induction of behavioral phenotypes in wild-type males following maternal Fmr1+/- has previously been reported. In the hypothalamus, there was a paternally-enhanced reduction in CYFIP1 protein whereas in the nucleus accumbens, there was a maternally-enhanced reduction in CYFIP1 protein. Nochange in FMR1 protein (FMRP) was observed in Cyfip1+/- mice, regardless of parental origin. To summarize, Cyfip1 haploinsufficiency increased compulsive-like behavior and induced genetic background-dependent, sex-dependent, and parent-of-origin-dependent effects on PF consumption and CYFIP1 expression that could have relevance for neurodevelopmental and neuropsychiatric disorders.

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Mindfulness, Compulsive Mobile Social Media Use, and Derived Stress: The Mediating Roles of Self-Esteem and Social Anxiety.

There is growing concern over the emergence of damaging compulsive use patterns among some users of social networking sites (SNSs), in particular of mobile social media. Although previous studies argue that mindfulness has a protective effect on compulsive behaviors, to date, no study has analyzed the underlying mechanisms by which mindfulness reduces compulsive SNS usage. This study addresses this gap by examining the relationship between mindfulness, self-esteem, social anxiety, compulsive mobile SNS usage, and derived stress in the context of the use of the mobile social media application, WhatsApp™. Mediation analysis supported the roles of self-esteem and social anxiety as mediators of the beneficial (lowering) effect of mindfulness on compulsive mobile SNS usage. Moreover, the results confirmed that compulsive mobile SNS use induces stress and that mindfulness has also lowering effects on stress derived from such compulsive behavior, mediated by the former variables. This research, therefore, provides a process explanation for the beneficial effect of mindfulness on stress derived from mobile social media use. Further theoretical and practical implications, as well as future research avenues, are discussed.