Bioremediation and bioscavenging for elimination of organophosphorus threats: An approach using enzymatic advancements.

Organophosphorus compounds (OP) are highly toxic pesticides and nerve agents widely used in agriculture and chemical warfare. The extensive use of these chemicals has severe environmental implications, such as contamination of soil, water bodies, and food chains, thus endangering ecosystems and biodiversity. Plants absorb pesticide residues, which then enter the food chain and accumulate in the body fat of both humans and animals. Numerous human cases of OP poisoning have been linked to both acute and long-term exposure to these toxic OP compounds. These compounds inhibit the action of the acetylcholinesterase enzyme (AChE) by phosphorylation, which prevents the breakdown of acetylcholine (ACh) neurotransmitter into choline and acetate. Thus, it becomes vital to cleanse the environment from these chemicals utilizing various physical, chemical, and biological methods. Biological methods encompassing bioremediation using immobilized microbes and enzymes have emerged as environment-friendly and cost-effective approaches for pesticide removal. Cell/enzyme immobilized systems offer higher stability, reusability, and ease of product recovery, making them ideal tools for OP bioremediation. Interestingly, enzymatic bioscavengers (stoichiometric, pseudo-catalytic, and catalytic) play a vital role in detoxifying pesticides from the human body. Catalytic bioscavenging enzymes such as Organophosphate Hydrolase, Organophosphorus acid anhydrolase, and Paraoxonase 1 show high degradation efficiency within the animal body as well as in the environment. Moreover, these enzymes can also be employed to decontaminate pesticides from food, ensuring food safety and thus minimizing human exposure. This review aims to provide insights to potential collaborators in research organizations, government bodies, and industries to bring advancements in the field of bioremediation and bioscavenging technologies for the mitigation of OP-induced health hazards.

Win and Loss Responses in the Monetary Incentive Delay Task Mediate the Link between Depression and Problem Drinking.

Depression and alcohol misuse, frequently comorbid, are associated with altered reward processing. However, no study has examined whether and how the neural markers of reward processing are shared between depression and alcohol misuse. We studied 43 otherwise-healthy drinking adults in a monetary incentive delay task (MIDT) during fMRI. All participants were evaluated with the Alcohol Use Disorders Identification Test (AUDIT) and Beck's Depression Inventory (BDI-II) to assess the severity of drinking and depression. We performed whole brain regressions against each AUDIT and BDI-II score to investigate the neural correlates and evaluated the findings at a corrected threshold. We performed mediation analyses to examine the inter-relationships between win/loss responses, alcohol misuse, and depression. AUDIT and BDI-II scores were positively correlated across subjects. Alcohol misuse and depression shared win-related activations in frontoparietal regions and parahippocampal gyri (PHG), and right superior temporal gyri (STG), as well as loss-related activations in the right PHG and STG, and midline cerebellum. These regional activities (ß's) completely mediated the correlations between BDI-II and AUDIT scores. The findings suggest shared neural correlates interlinking depression and problem drinking both during win and loss processing and provide evidence for co-morbid etiological processes of depressive and alcohol use disorders.

Overnight Abstinence Is Associated With Smaller Secondary Somatosensory Cortical Volumes and Higher Somatosensory-Motor Cortical Functional Connectivity in Cigarette Smokers.

INTRODUCTION: Abstinence symptoms present challenges to successful cessation of cigarette smoking. Chronic exposure to nicotine and long-term nicotine abstinence are associated with alterations in cortical and subcortical gray matter volumes (GMVs). AIMS AND METHODS: We aimed at examining changes in regional GMVs following overnight abstinence and how these regional functions relate to abstinence symptoms. Here, in a sample of 31 regular smokers scanned both in a satiety state and after overnight abstinence, we employed voxel-wise morphometry and resting-state functional connectivity (rsFC) to investigate these issues. We processed imaging data with published routines and evaluated the results with a corrected threshold. RESULTS: Smokers showed smaller GMVs of the left ventral hippocampus and right secondary somatosensory cortex (SII) after overnight abstinence as compared to satiety. The GMV alterations in right SII were positively correlated with changes in withdrawal symptom severity between states. Furthermore, right SII rsFC with the precentral gyrus was stronger in abstinence as compared to satiety. The inter-regional rsFC was positively correlated with motor impulsivity and withdrawal symptom severity during abstinence and negatively with craving to smoke during satiety. CONCLUSIONS: These findings highlight for the first time the effects of overnight abstinence on cerebral volumetrics and changes in functional connectivity of a higher-order sensory cortex. These changes may dispose smokers to impulsive behaviors and aggravate the urge to smoke at the earliest stage of withdrawal from nicotine. IMPLICATIONS: Overnight abstinence leads to changes in gray matter volumes and functional connectivity of the second somatosensory cortex in cigarette smokers. Higher somatosensory and motor cortical connectivity in abstinence is significantly correlated with trait motor impulsivity and withdrawal symptom severity. The findings add to the literature of neural markers of nicotine addiction.

Reward-Related Responses and Tonic Craving in Cocaine Addiction: An Imaging Study of the Monetary Incentive Delay Task.

BACKGROUND: Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses were mixed, and few studies have examined whether reward responses relate to tonic cocaine craving. METHODS: We combined functional magnetic resonance imaging and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines, and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine-dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. RESULTS: The VS showed higher activation to large as compared with small or no wins, but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. CONCLUSIONS: The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving, and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug-seeking behavior in addicted individuals.

Perceived friendship and binge drinking in young adults: A study of the Human Connectome Project data.

BACKGROUND: Peer influences figure prominently in young adult binge drinking. Women have trended to show a level of alcohol use on par with men during the last decades. It would be of interest to investigate the neural processes of social cognition that may underlie binge drinking and the potential sex differences. METHODS: Here, we examined the data of the Human Connectome Project where we identified a total of 175 binge drinkers (125 men) and 285 non-binge drinkers (97 men) performing a social cognition task during brain imaging. We analyzed the imaging data with published routines and evaluated the results at a corrected threshold. RESULTS: Both male and female binge relative to non-binge drinkers showed higher perceived friendship. Binge relative to non-binge drinkers demonstrated diminished activations in the anterior medial orbitofrontal cortex (amOFC) during perception of social vs. random interaction, with a more prominent effect size in women. Further, whole-brain regression identified activity of the right posterior insula (rPI) in negative correlation with perceived friendship score in non-binge drinking women. Post-hoc analyses showed significant correlation of rPI activity with perceived friendship, amOFC activity, and a summary measure of alcohol use severity identified by principal component analysis, across all subjects. Mediation and path analysis demonstrated a significant model: amOFC activity → rPI activity → perceived friendship → severity of alcohol use. CONCLUSIONS: These findings support peer influences on binge drinking and suggest neural correlates that may relate altered social cognitive processing to alcohol misuse in young adults.

Sex differences in neural responses to reward and the influences of individual reward and punishment sensitivity.

BACKGROUND: Men and women show differences in sensitivity to reward and punishment, which may impact behavior in health and disease. However, the neural bases of these sex differences remain under-investigated. Here, by combining functional magnetic resonance imaging (fMRI) and a variant of the Monetary Incentive Delay Task (MIDT), we examined sex differences in the neural responses to wins and losses and how individual reward and punishment sensitivity modulates these regional activities. METHODS: Thirty-sex men and 27 women participated in the fMRI study. We assessed sensitivity to punishment (SP) and sensitivity to reward (SR) with the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). In the MIDT, participants pressed a button to collect reward ($1, 1¢, or nil), with the reaction time window titrated across trials so participants achieved a success rate of approximately 67%. We processed the Imaging data with published routines and evaluated the results with a corrected threshold. RESULTS: Women showed higher SP score than men and men showed higher SR score than women. Men relative to women showed higher response to the receipt of dollar or cent reward in bilateral orbitofrontal and visual cortex. Men as compared to women also showed higher response to dollar loss in bilateral orbitofrontal cortex. Further, in whole-brain regressions, women relative to men demonstrated more significant modulation by SP in the neural responses to wins and larger wins, and the sex differences were confirmed by slope tests. CONCLUSIONS: Together, men showed higher SR and neural sensitivity to both wins, large or small, and losses than women. Individual differences in SP were associated with diminished neural responses to wins and larger wins in women only. These findings highlight how men and women may differ in reward-related brain activations in the MIDT and add to the imaging literature of sex differences in cognitive and affective functions.

Midcingulate Cortical Activations Interrelate Chronic Craving and Physiological Responses to Negative Emotions in Cocaine Addiction.

BACKGROUND: Negative emotions precipitate drug craving. Individuals vary in how they engage in negative emotions, as may be reflected in physiological arousal elicited by the emotions. It remains unclear whether physiological responses to negative emotions relate to cocaine craving and how regional brain activations support this relationship. METHODS: We examined brain activation and skin conductance responses (SCRs) among 40 cocaine-dependent (CD) subjects and 37 healthy control subjects during exposure to negative-emotional and neutral images. Imaging and SCR data were processed with published routines, and the results were evaluated at a corrected threshold. RESULTS: Relative to control subjects, CD subjects showed increased activation in the hippocampus, inferior parietal gyrus, and caudate in response to negative-emotional versus neutral images. CD subjects relative to control subjects showed diminished SCR to negative-emotional versus neutral images, and the difference (SCRNE-NU) was positively correlated with chronic craving, as evaluated by the Cocaine Craving Questionnaire, and craving rating (negative-emotional - neutral), in CD subjects. Activations of the midcingulate cortex (MCC) were positively correlated with both chronic cocaine craving and SCRNE-NU and completely mediated the correlation between chronic cocaine craving and SCRNE-NU. Further, path analyses suggested a directional influence of SCRNE-NU on craving rating (negative-emotional - neutral): chronic craving → MCC activation → SCRNE-NU → craving rating. CONCLUSIONS: CD subjects demonstrate hypoactive SCRs to negative emotions. Less diminution of SCR is associated with higher cocaine craving and MCC response to negative emotions. A hub of the limbic motor circuit, the MCC may translate chronic cocaine craving into physiological responses that precipitate cocaine seeking.

The Diagnostic Criteria for Chronic Endometritis: A Survey of Pathologists.

While acute endometritis is a reasonably well-defined entity of ascending infection and attendant active inflammation, chronic endometritis is less well defined. As part of a broad effort to define and refine the diagnostic criteria and management of the disease, we conducted a survey of pathologists to understand the variability in diagnostic criteria and implications of the diagnosis of nonspecific, nonobstetric chronic endometritis. Members of national and international professional pathology societies were surveyed utilizing anonymous electronic surveys designed to examine diagnostic criteria, etiological understanding and treatment implications of a pathologic diagnosis of nonspecific, nonobstetric chronic endometritis. There was substantial variability among pathologists in the diagnostic criteria used for making a diagnosis of nonspecific, nonobstetric chronic endometritis, with 28.5% of pathologists using the presence of a single plasma cell for making the diagnosis. There was additional variability in the use of special stains, reporting in the presence of coexisting lesions and the hormonal stage of the endometrium. There were no differences between generalists and specialists in the diagnostic criteria used, except the significantly greater likelihood of specialists making the diagnosis in gestational endometrium. The substantial variability in diagnostic criteria for nonspecific, nonobstetric chronic endometritis among pathologists, including among gynecologic pathologists, has the potential to confound the management of patients. Standardization of diagnostic criteria for chronic endometritis is essential to understand the implications of the diagnosis.

Resting state hypothalamic and dorsomedial prefrontal cortical connectivity of the periaqueductal gray in cocaine addiction.

Cocaine-dependent (CD) individuals demonstrate significant anxiety and dysphoria during withdrawal, a negative emotional state that may perpetuate drug seeking and consumption. An extensive body of work has focused on characterizing reward circuit dysfunction, but relatively little is known about the pain circuit during cocaine withdrawal. In an earlier study, we highlighted how cue-elicited functional connectivity between the periaqueductal gray (PAG), a subcortical hub of the pain circuit, and ventromedial prefrontal cortex supports tonic craving in recently abstinent CD. The functional organization of the brain can be characterized by intrinsic connectivities, and it is highly likely that the resting state functional connectivity (rsFC) of the PAG may also be altered in association with cocaine use variables. Here, we examined this issue in 52 CD and 52 healthy control (HC) participants. Imaging data were processed with published routines, and the findings were evaluated with a corrected threshold. In a covariance analysis, CD as compared with HC showed higher PAG rsFC with the hypothalamus, dorsomedial prefrontal, and inferior parietal cortices. Further, these connectivities were correlated negatively with tonic cocaine craving and recent cocaine use, respectively. Higher hypothalamic and frontoparietal rsFC with the PAG may reflect a compensatory process to regulate craving and compulsive drug use. The findings provide additional evidence in humans implicating the PAG circuit and may help research of the role of negative reinforcement in sustaining habitual drug use in cocaine addiction.

The Neural Processes Interlinking Social Isolation, Social Support, and Problem Alcohol Use.

BACKGROUND: Subjective feeling of social isolation, as can be measured by perceived burdensomeness (PB), is a major risk factor for alcohol misuse. Heightened PB is associated with elevated stress response and diminished cognitive control, both of which contribute to problem drinking. Here, we sought to identify the neural substrates underlying the relationship between PB and alcohol misuse. METHODS: We employed resting-state functional magnetic resonance imaging data collected from 61 problem drinkers to characterize the functional connectivity of the hypothalamus and ventral striatum (VS) in relation to PB. We specifically examined whether the connectivities of the hypothalamus and VS were differentially influenced by PB to produce contrasting effects on alcohol use. Finally, we evaluated how individual differences in social support modulate the inter-relationships of social isolation, neural connectivity, and the severity of problem drinking. RESULTS: Whole-brain multiple regressions show a positive relationship between PB and hypothalamic connectivity with the hippocampus and an inverse pattern for VS connectivity with the middle frontal gyrus. Difference in strength between the 2 connectivities predicted the severity of problem drinking, suggesting an imbalance involving elevated hypothalamic and diminished prefrontal cortical modulation in socially isolated problem drinkers. A path analysis further revealed that the lack of social support was associated with a bias toward low prefrontal connectivity, which in turn increased PB and facilitated problem drinking. CONCLUSIONS: Altered hypothalamus and VS connectivity may underlie problem drinking induced by social isolation. The current findings also highlight the important role of social support as a potential protective factor against alcohol misuse.

Sex Differences in Neural Responses to the Perception of Social Interactions.

Social interaction is critical to emotional well-being. Previous studies have suggested sex differences in the perception of social interaction. However, the findings depend on the nature of interactions and whether it involves facial emotions. Here, we explored sex differences in neural responses to the perception of social interaction using the Human Connectome Project data. Participants (n = 969, 505 women) were engaged in a social cognition task with geometric objects moving and colliding to simulate social interaction. Behaviorally, men relative to women demonstrated higher accuracy in perceiving social vs. random interactions. Men vs. women showed higher activation in the right superior temporal gyrus, bilateral occipital and posterior cingulate cortex and precuneus, and women vs. men showed higher activation in the right inferior frontal cortex, during exposure to social vs. random interactions. In whole-brain regressions, the differences in accuracy rate in identifying social vs. random interactions (AR SOC - AR RAN ) were associated with higher activation in the paracentral lobule (PCL) and lower activation in bilateral anterior insula (AI), pre-supplementary motor area (preSMA), and left middle frontal gyrus (MFG) in men and women combined, lower activation in bilateral AI, preSMA and left MFG in men alone, and higher activation in the PCL and the medial orbitofrontal cortex in women alone. The latter sex differences were confirmed by slope tests. Further, the PCL activity mediated the correlation between an internalizing syndromal score, as assessed by the Achenbach Self-Report, and (AR SOC - AR RAN ) across all subjects. These findings highlighted sex differences in the behavioral and neural processes underlying the perception of social interaction, as well as the influence of internalizing traits on these processes.

Cue-elicited functional connectivity of the periaqueductal gray and tonic cocaine craving.

BACKGROUND: Withdrawal from chronic cocaine use leads to anxiety and dysphoria that may perpetuate habitual drug use. The pain circuit is widely implicated in the processing and manifestations of negative emotions. Numerous studies have focused on characterizing reward circuit dysfunction but relatively little is known about the pain circuit response during cocaine withdrawal. METHODS: Here we examined the activity and connectivity of the periaqueductal gray (PAG), a hub of the pain circuit, during cocaine cue exposure in 52 recently abstinent cocaine dependent participants (CD, 42 men). Imaging data were processed with published routines, and the results were evaluated at a corrected threshold. RESULTS: CD showed higher activation of the PAG and connectivity of the PAG with the ventromedial prefrontal cortex (vmPFC) during cocaine as compared to neutral cue exposure. PAG-vmPFC connectivity was positively and negatively correlated with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire, in male and female CD, respectively, and the sex difference was confirmed by a slope test. Granger causality analyses showed that the PAG Granger caused vmPFC time series in men and the reverse was true in women, substantiating sex differences in the directional interactions of the PAG and vmPFC. CONCLUSION: The findings provide the first evidence in humans implicating the PAG circuit in cocaine withdrawal and cocaine craving and advance our understanding of the role of the pain circuit and negative reinforcement in sustaining habitual drug use in cocaine addiction.

Interpersonal Risk Factors for Suicide in Cocaine Dependence: Association with Self-Esteem, Personality Traits, and Childhood Abuse.

OBJECTIVE: Studies have linked cocaine dependence to suicidality. According to the Interpersonal Theory of Suicide, suicidal behavior becomes likely with the simultaneous presence of perceived burdensomeness (PB), lack of (or thwarted) belongingness (TB), and acquired fearlessness about death (FAD). Here, we examined personality and other variables, including depression, self-esteem, childhood abuse, and substance use, as predictors of these risk factors in cocaine-dependent individuals (CDs). METHODS: Seventy CDs and 70 healthy controls (HCs) participated. We examined group differences in a group-by-sex analysis of variance and identified predictors of PB, TB, and FAD in stepwise regressions. RESULTS: CDs exhibited elevated PB and TB but not FAD, compared to HCs. CDs also exhibited elevated harm avoidance, novelty seeking, depression, and lower self-esteem and reward dependence. Females reported elevated sexual abuse, harm avoidance, reward dependence, depression, but lower FAD, relative to males, among CDs and HCs. Among CDs, PB was predicted by lower self-esteem and greater emotional abuse; TB was predicted by lower self-esteem and reward dependence, as well as greater emotional and sexual abuse; and FAD was predicted by lower harm avoidance and greater physical abuse. CONCLUSIONS: Interventions targeting suicidality in cocaine dependence should take into consideration self-esteem, personality traits, and childhood abuse.

Interdependent Neural Correlates of Reward and Punishment Sensitivity During Rewarded Action and Inhibition of Action.

Imaging studies have distinguished the brain correlates of approach and avoidance behaviors and suggested the influence of individual differences in trait sensitivity to reward (SR) and punishment (SP) on these neural processes. Theoretical work of reinforcement sensitivity postulates that SR and SP may interdependently regulate behavior. Here, we examined the distinct and interrelated neural substrates underlying rewarded action versus inhibition of action in relation to SR and SP as evaluated by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Forty-nine healthy adults performed a reward go/no-go task with approximately 2/3 go and 1/3 no-go trials. Correct go and no-go responses were rewarded and incorrect responses were penalized. The results showed that SR and SP modulated rewarded go and no-go, respectively, both by recruiting the rostral anterior cingulate cortex and left middle frontal gyrus (rACC/left MFG). Importantly, SR and SP influenced these regional activations in opposite directions, thus exhibiting an antagonistic relationship as suggested by the reinforcement sensitivity theory. Furthermore, mediation analysis revealed that heightened SR contributed to higher rewarded go success rate via enhanced rACC/left MFG activity. The findings demonstrate interrelated neural correlates of SR and SP to support the diametric processes of behavioral approach and avoidance.

The effects of age on reward magnitude processing in the monetary incentive delay task.

Previous studies have suggested age-related differences in reward-directed behavior and cerebral processes in support of the age effects. However, it remains unclear how age may influence the processing of reward magnitude. Here, with 54 volunteers (22-74 years of age) participating in the Monetary Incentive Delay Task (MIDT) with explicit cues ($1, ¢1, or nil) and timed response to win, we characterized brain activations during anticipation and feedback and the effects of age on these regional activations. Behaviorally, age was associated with less reaction time (RT) difference between dollar and cent trials, as a result of slower response to the dollar trials; i.e., age was positively correlated with RT dollar - RT cent, with RT nil as a covariate. Both age and the RT difference ($1 - ¢1) were correlated with diminished activation of the right caudate head, right anterior insula, supplementary motor area (SMA)/pre-SMA, visual cortex, parahippocampal gyrus, right superior/middle frontal gyri, and left primary motor cortex during anticipation of $1 vs. ¢1 reward. Further, these regional activities mediated the age effects on RT differences. In responses to outcomes, age was associated with decreases in regional activations to dollar vs. cent loss but only because of higher age-related responses to cent losses. Together, these findings suggest age-related differences in sensitivity to the magnitude of reward. With lower cerebral responses during anticipation to win large rewards and higher responses to outcomes of small loss, aging incurs a constricted sensitivity to the magnitude of reward.

Reward sensitivity and electrodermal responses to actions and outcomes in a go/no-go task.

Skin conductance response (SCR) is used in psychophysiological research to measure the reactions of the autonomic nervous system to reward and punishment. While there is consistent evidence that SCR increases to both aversive and appetitive stimuli, it remains unclear whether SCR simply represents a general index of arousal to motivationally significant outcomes or may also differentiate action or inhibition of action that lead to such outcomes. Furthermore, individual differences in trait sensitivity to reward and punishment can influence physiological arousal during approach and avoidance behaviors. Yet, their inter-relationships have not been examined. To address these gaps, we employed a reward go/no-go task with ⅔ go and ⅓ no-go trials and an individually titrated go response window. Correct go and no-go responses were rewarded while incorrect responses were penalized. We examined whether SCR varied with outcome (win vs. loss), action (go vs. no-go), and individual differences in reward sensitivity (SR) and sex. The results showed greater SCRs to loss vs. win, to go vs. no-go success, and to go success in positive correlation with SR. Further, SCR mediated the relationship between SR and go success rate. In sex differences, men exhibited greater SCR which was more predictive of go success rate relative to women. In contrast, SCR was more predictive of no-go success rate in women. Thus, SCR varies according to behavioral contingency, outcome, sex, and reward sensitivity. These findings add to the literature by characterizing the individual and behavioral factors that may influence physiological arousal in response to salient events.

Cue-elicited craving, thalamic activity, and physiological arousal in adult non-dependent drinkers.

Changes in physiological arousal frequently accompany cognitive and affective challenges. Many studies employed cue exposure paradigms to investigate the neural processes underlying cue-elicited drug and alcohol craving. However, whether cue-elicited craving relates to changes in physiological arousal and the neural bases underlying the potential relationship remain unclear. Here we examined cerebral cue-related activations in relation to differences in skin conductance responses (SCR) recorded during alcohol vs. neutral cue blocks in 61 non-dependent alcohol drinkers (30 men). Imaging and skin conductance data were collected and processed with published routines. Mediation analyses were conducted to examine the inter-relationship between regional activities, cue-elicited craving, and SCR. The results showed higher SCR during alcohol than during neutral cue exposure. Despite no differences in drinking characteristics, men as compared to women demonstrated higher craving rating, and men but not women demonstrated a positive correlation between alcohol (vs. neutral) cue-evoked craving and SCR. Further, across subjects, thalamic cue activity was positively correlated with differences in SCR between alcohol and neutral cue blocks in men but not in women. Mediation analyses suggested that thalamic activity mediated the correlation between craving and SCR across men and women, and in men but not women alone. These findings substantiate physiological and neural correlates of alcohol cue response and suggest important sex differences in the physiological and neural processes of cue evoked craving. Centered on the intralaminar and mediodorsal subregions, the thalamic correlate may represent a neural target for behavioral or pharmacological therapy to decrease cue-elicited arousal and craving.

Gender differences in obsessive-compulsive disorder: Findings from a multicentric study from India.

Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous. Gender is an important factor mediating this heterogeneity. We examined gender differences in a large sample (n = 945) of OCD patients under a multi-centric study in India. Cross-sectional assessments were done on consecutive adult (>18 years) treatment-seeking patients with a DSM-5 diagnosis of OCD. Subjects were assessed on Structured Clinical Interview for DSM-5-Research Version for comorbid psychiatric illnesses, Yale Brown Obsessive Compulsive Scale for OCD phenomenology and symptom severity, Brown Assessment of Beliefs Scale for insight, Beck's Depression Inventory for severity of depressive symptoms, and the Obsessive Beliefs Questionnaire. On multivariate backward Wald logistic regression analysis, males (59.7%) had more years of education, had a higher rate of checking compulsions and comorbid substance use disorders. Women were more likely to be married, more commonly reported precipitating factors, had a higher rate of hoarding compulsions and comorbid agoraphobia. Findings from this large study validate gender as an important mediator of phenotypic heterogeneity in OCD. The mechanistic basis for these differences might involve complex interactions between biological, cultural and environmental factors.

Presurgical language fMRI: Technical practices in epilepsy surgical planning.

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.