Understanding cingulotomy's therapeutic effect in OCD through computer models.

Cingulotomy is therapeutic in OCD, but what are the possible mechanisms? Computer models that formalize cortical OCD abnormalities and anterior cingulate cortex (ACC) function can help answer this. At the neural dynamics level, cortical dynamics in OCD have been modeled using attractor networks, where activity patterns resistant to change denote the inability to switch to new patterns, which can reflect inflexible thinking patterns or behaviors. From that perspective, cingulotomy might reduce the influence of difficult-to-escape ACC attractor dynamics on other cortical areas. At the functional level, computer formulations based on model-free reinforcement learning (RL) have been used to describe the multitude of phenomena ACC is involved in, such as tracking the timing of expected outcomes and estimating the cost of exerting cognitive control and effort. Different elements of model-free RL models of ACC could be affected by the inflexible cortical dynamics, making it challenging to update their values. An agent can also use a world model, a representation of how the states of the world change, to plan its actions, through model-based RL. OCD has been hypothesized to be driven by reduced certainty of how the brain's world model describes changes. Cingulotomy might improve such uncertainties about the world and one's actions, making it possible to trust the outcomes of these actions more and thus reduce the urge to collect more sensory information in the form of compulsions. Connecting the neural dynamics models with the functional formulations can provide new ways of understanding the role of ACC in OCD, with potential therapeutic insights.

Hypnotic predictors of agency: Responsiveness to specific suggestions in hypnosis is associated with involuntariness in fibromyalgia.

Hypnosis is associated with alterations in the sense of agency which can play a role in its utilization as a nonpharmacological option for pain management. The goal of the current study was to examine the relationships between responsiveness to suggestions in hypnosis and alterations of the sense of agency among patients with fibromyalgia. Ninety-eight participants with fibromyalgia underwent two hypnotizability assessments followed by the Sense of Agency Rating Scale. Clinical pain measures were also collected. Involuntariness was predicted by responsiveness to control, ideomotor, and dissociation suggestions. Effortlessness was predicted by responsiveness to control and ideomotor suggestions, and age. Hypnotizability was associated with main clinical pain outcomes, but agency alterations were not. Results suggest a shared mechanism between responsiveness to specific suggestions and the sense of agency in hypnosis. We discuss theoretical and clinical implications for pain management and the need for further research.

Improvements in error-monitoring and symptoms following low-frequency rTMS of dorsal anterior cingulate cortex in obsessive compulsive disorder; a randomized, sham-controlled study.

Action monitoring deficit is a core underlying characteristic and endophenotype of Obsessive Compulsive Disorder (OCD). Dorsal anterior cingulate cortex (dACC) is heavily involved in error monitoring and cognitive control, and the hyperactivity in this region is associated with OCD symptom severity. This study aimed to test whether low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) targeting dACC improves both error-monitoring performance and OCD symptoms in a randomized, sham-controlled, double-blind trial design. 20 OCD patients were randomly assigned to receive 20 sessions of Active (n = 10) or Sham (n = 10) rTMS administered twice-daily. Error-monitoring performance and symptom severity were measured pre- and post-treatment using Erikson Flanker tasks and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with three month symptom follow-up. Following active-but not sham-rTMS, patients showed improved response time for incongruent stimuli, trials following a correct response, and for reporting and correcting errors. Significant OCD symptom improvement was observed at one-month follow-up for patients who received Active (28.0% reduction) but not Sham (11.7% reduction) stimulation. In OCD patients, LF rTMS of the dACC can simultaneously improve on-line adjustment of behaviour-by enhancing the capacity for rapid error monitoring-and clinical symptoms, suggesting a link between error monitoring impairment and OCD pathophysiology.

Orbitofrontal cortex volume prospectively predicts cannabis and other substance use onset in adolescents.

BACKGROUND: Identifying neural characteristics that predict cannabis initiation is important for prevention efforts. The orbitofrontal cortex is critical for reward response and may be vulnerable to substance-induced alterations. AIMS: We measured orbitofrontal cortex thickness, surface area, and volume prior to the onset of use to predict cannabis involvement during an average nine-year follow-up. METHODS: Adolescents (n=118) aged 12-15 years completed baseline behavioral assessment and magnetic resonance imaging scans, then were followed up to 13 years with annual substance use interviews. Logistic regression examined baseline (pre-substance use) bilateral medial and lateral orbitofrontal cortex characteristics (volume, surface area, or cortex thickness) as predictors of regular cannabis use by follow-up. Post-hoc multinomial logistic regression assessed whether orbitofrontal cortex characteristics significantly predicted either alcohol use alone or cannabis+alcohol co-use. Brain-behavior relationships were assessed through follow-up correlations of baseline relationships between orbitofrontal cortex and executive functioning, reward responsiveness, and behavioral approach traits. RESULTS: Larger left lateral orbitofrontal cortex volume predicted classification as cannabis user by follow-up (p=0.025, odds ratio=1.808). Lateral orbitofrontal cortex volume also predicted cannabis+alcohol co-user status (p=0.008, odds ratio=2.588), but not alcohol only status. Larger lateral orbitofrontal cortex volume positively correlated with greater baseline reward responsiveness (p=0.030, r=0.348). There were no significant results by surface area or cortex thickness (ps>0.05). CONCLUSIONS: Larger left lateral orbitofrontal cortex measured from ages 12-15 years and prior to initiation of substance use was related to greater reward responsiveness at baseline and predicted classification as a cannabis user and cannabis+alcohol co-user by final follow-up. Larger lateral orbitofrontal cortex volume may represent aberrant orbitofrontal cortex maturation and increasing vulnerability for later substance use.

Cocaine cue-induced dopamine release in the human prefrontal cortex.

BACKGROUND: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. METHODS: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. RESULTS: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. LIMITATIONS: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. CONCLUSION: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.

Cocaine cue-induced dopamine release in amygdala and hippocampus: a high-resolution PET [¹8F]fallypride study in cocaine dependent participants.

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [(18)F]fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6 ± 8.0 years; years of cocaine use: 15.9 ± 7.4) underwent two [(18)F]fallypride high-resolution research tomography-PET scans, one with exposure to neutral cues and one with cocaine cues. [(18)F]Fallypride non-displaceable-binding potential (BPND) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BPND values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala: p=0.040, and right hippocampus: p=0.025). Individual differences in the cue-induced craving response predicted the magnitude of [(18)F]fallypride responses within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589, p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior.

Sexual function and psychological status among males and females with ischemic heart disease.

INTRODUCTION: Patients with coronary artery disease (CAD) may also suffer from mental and sexual problems, and we should consider the mutual influence such conditions have on each other. However, the interrelation between sexual and mental problems in the context of CAD has not been fully investigated, especially when it comes to gender. AIM: Our aim was to evaluate sexuality and psychiatric symptoms among patients with CAD and the relation between them in each gender. METHODS: In this cross-sectional study, 550 (397 men and 153 women) patients with documented CAD were surveyed for anxiety and depression using the hospital anxiety and depression scale (HADS) self-administered questionnaire as well as the relation and sexuality scale (RSS). Three subscores were calculated for sexual function, frequency, and fear, with higher scores indicative of a poorer condition. MAIN OUTCOME MEASURES: The HADS and the RSS. RESULTS: Depressive symptoms and anxiety were more severe among our female subjects than they were among the male ones. In addition, the scores for sexual frequency, sexual function, and the total RSS were significantly higher in women, while men had a significantly higher score for sexual fear. The total RSS score correlated with depressive symptoms in women (r = 0.19, P = 0.03), but not in the male subjects. Considering the subscores, a higher score for sexual frequency correlated with depressive symptoms in both genders; however, being afraid of sexual relation correlated with depressive symptoms only in men with CAD and their spouses (r = 0.18, P = 0.001). CONCLUSION: We found that women with CAD have poorer sexual relation and more severe depressive symptoms than men do. Among men with CAD and their wives, fear of sexual relationship is a more serious problem. Such gender-specific characteristics and their interrelations ought to receive due consideration in the management of CAD.

Gender impact on the correlation between sexuality and marital relation quality in patients with coronary artery disease.

INTRODUCTION: Although the negative impact of coronary artery disease (CAD) on sexual and marital relation of the patients is known, data are lacking regarding possible gender difference. AIM: We designed a study on patients with CAD to investigate sexual relation and marital adjustment and their association with regard to gender differences. MAIN OUTCOME MEASURES: Questionnaires including the Dyadic Adjustment Scale for evaluating the couple's agreement on decisions and appropriate behavior, marital satisfaction, and marital cohesion, and the Relation and Sexuality Scale (RSS) for sexual function, frequency, and fear. METHODS: We surveyed 650 patients with documented CAD without any other major comorbidities. RESULTS: The patients were 464 men (73.1%) and 171 women (26.9%) with CAD. The mean age of the men and the women were 57.1 +/- 11.6 years and 56.3 +/- 9.7 years, respectively. The women had a significantly poorer dyadic adjustment and sexual relation than men, except for sexual fear, which was more prominent in men with CAD and their spouses. The sexual frequency and the total RSS scores correlated with all aspects of the patients' marital relation in both genders. However, only men suffered from a poorer dyadic satisfaction, dyadic consensus, affectional expression, and overall marital adjustment if they were more afraid of sexual relation. In women, but not men, sexual function was significantly associated with their dyadic satisfaction and their overall marital relation. CONCLUSIONS: Poorer sexual relation and marital adjustment was detected in our women with CAD. To manage all the problems of the patients that may impact their cardiac status, we should consider factors such as fear of sexual activity in men sexual dysfunction in women, and their correlation with marital adjustment.