Trials in women.

Women of childbearing age have been viewed as a 'vulnerable population' and have been systematically excluded from early clinical trials. A change in attitude and policies occurred in the last decade, with a consequent increase of women participating in clinical trials. The implications are increasing respect for the woman's capacity to make her own risk-benefit choices, early evaluation of patients that represent the ultimate user of a drug and equal opportunities for women to benefit from the therapeutic potential of new drugs. Drug trials should be designed to identify sex-related effects and to analyse the efficacy and tolerability of antiepileptic drugs (AEDs) by gender. Further aspects should be considered, including changes in response in relation to the menstrual cycle and over the various stages of reproductive life; interactions between hormonal therapies and AEDs; the effect of AEDs on reproductive function and possible consequences of prenatal exposure to AEDs. These considerations become even more critical when pregnant and lactating women are considered, since any risk for the offspring is unacceptable unless drug administration is likely to have major medical benefits for the mother.     

Emotional reactions in moral decision-making are influenced by empathy and alexithymia

The role of emotional processes in driving moral choices remains debated. In particular, diminished emotional processing and reduced empathy have been associated with unusual high rates of utilitarian responses in moral judgments while, to date, the effects of diminished emotional processing and empathy on moral decision-making have been only partially considered. In this study, we investigated the influence of empathy and alexithymia on behavior and emotional responses while participants performed a moral decision task. Self-report (valence and arousal ratings) and physiological (skin conductance and heart rate) measures were collected during the task. Results showed that empathy and alexithymia shaped emotional reactions to moral decisions but did not bias moral choices. The more empathic the participants, the more dilemmas were perceived as unpleasant and arousing, and the greater the increase in skin conductance. Conversely, alexithymia was characterized by a reduced physiological activation during moral decisions, but normal self-report ratings. Heart rate was not modulated by empathy or alexithymia. These results add new evidence to the field of moral decision showing that empathy and alexithymia modulate emotional reactions to moral decision.     

Pregnancy-related knowledge,risk perception,and reproductive decision making of women with epilepsy in Korea

PurposeTo determine the influence of pregnancy-related knowledge and the risk perception on reproductive decision making in women with epilepsy.MethodsWe enrolled women with epilepsy, who were of reproductive age and were considering having children in the future. A questionnaire was used to assess the level of pregnancy-related knowledge, perception of the offspring's risk for developing epilepsy or for having a congenial anomaly, and discussion with a physician concerning pregnancy-related issues. We evaluated the following outcome variables: (1) the decision to discontinue anti-epileptic drug (AED) during a future pregnancy regardless of the medical indication; and (2) the decision to have fewer children because of epilepsy.ResultsWe enrolled a total of 186 women with epilepsy. (1) Fifty-eight percent of the women were considering discontinuing AED during a future pregnancy regardless of the medical indication, and 25% of the women decided to have fewer children because of epilepsy. (2) The decision to discontinue AED during a future pregnancy was associated with low-level pregnancy-related knowledge. (3) The decision to have fewer children because of epilepsy was associated with an exaggerated perception of the offspring's risk for developing epilepsy. (4) The women who had ever discussed pregnancy-related issues with their physician were less likely to decide to discontinue AED during a future pregnancy; however, a discussion on this issue had no impact on their decision to have fewer children because of epilepsy.ConclusionMore than 50% of the women would decide to discontinue AED during a future pregnancy, and 25% of the women stated that they would have fewer children because of epilepsy. These data highlight the importance of education on pregnancy-related issues and genetic risk counseling.     

Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition.

BACKGROUND: Choosing between actions associated with uncertain rewards and punishments is mediated by neural circuitry encompassing the orbitofrontal cortex, anterior cingulate cortex (ACC), and striatum; however, the precise conditions under which these different components are activated during decision-making cognition remain uncertain. METHODS: Fourteen healthy volunteers completed an event-based functional magnetic resonance imaging protocol to investigate blood-oxygenation-level-dependent (BOLD) responses during independently modeled phases of choice cognition. In the "decision phase," participants decided which of two simultaneous visually presented gambles they wished to play for monetary reward. The gambles differed in their magnitude of gains, magnitude of losses, and the probabilities with which these outcomes were delivered. In the "outcome phase," the result of each choice was indicated on the visual display. RESULTS: In the decision phase, choices involving large gains were associated with increased BOLD responses in the pregenual ACC, paracingulate, and right posterior orbitolateral cortex compared with choices involving small gains. In the outcome phase, good outcomes were associated with increased BOLD responses in the posterior orbitomedial cortex, subcallosal ACC, and ventral striatum compared with negative outcomes. There was only limited overlap between reward-related activity in ACC and orbitofrontal cortex during the decision and outcome phases. CONCLUSIONS: Neural activity within the medial and lateral orbitofrontal cortex, pregenual ACC, and striatum mediate distinct representations of reward-related information that are deployed at different stages during a decision-making episode.     

Social decision‐making in the brain: Input‐state‐output modelling reveals patterns of effective connectivity underlying reciprocal choices

During social interactions, decision‐making involves mutual reciprocity—each individual's choices are simultaneously a consequence of, and antecedent to those of their interaction partner. Neuroeconomic research has begun to unveil the brain networks underpinning social decision‐making, but we know little about the patterns of neural connectivity within them that give rise to reciprocal choices. To investigate this, the present study measured the behaviour and brain function of pairs of individuals (N = 66) whilst they played multiple rounds of economic exchange comprising an iterated ultimatum game. During these exchanges, both players could attempt to maximise their overall monetary gain by reciprocating their opponent's prior behaviour—they could promote generosity by rewarding it, and/or discourage unfair play through retaliation. By adapting a model of reciprocity from experimental economics, we show that players' choices on each exchange are captured accurately by estimating their expected utility (EU) as a reciprocal reaction to their opponent's prior behaviour. We then demonstrate neural responses that map onto these reciprocal choices in two brain regions implicated in social decision‐making: right anterior insula (AI) and anterior/anterior‐mid cingulate cortex (aMCC). Finally, with behavioural Dynamic Causal Modelling, we identified player‐specific patterns of effective connectivity between these brain regions with which we estimated each player's choices with over 70% accuracy; namely, bidirectional connections between AI and aMCC that are modulated differentially by estimates of EU from our reciprocity model. This input‐state‐output modelling procedure therefore reveals systematic brain–behaviour relationships associated with the reciprocal choices characterising interactive social decision‐making.     

Expecting social punishment facilitates control over a decision under uncertainty by recruiting medial prefrontal cortex

In many decision-making situations, sub-optimal choices are increased by uncertainty. However, when wrong choices could lead to social punishment, such as blame, people might try to improve their performance by minimizing sub-optimal choices, which could be achieved by increasing the subjective cost of errors, thereby globally reducing decision noise or reducing an uncertainty-induced component of decision noise. In this functional magnetic resonance imaging (fMRI) study, 46 participants performed a choice task in which the probability of a correct choice with a given cue and the conditional probability of blame feedback (by making an incorrect choice) changed continuously. By comparing computational models of behaviour, we found that participants optimized their performance by preferentially reducing a component of decision noise associated with uncertainty. Simultaneously, expecting blame significantly deteriorated participants’ mood. Model-based fMRI analyses and dynamic causal modelling indicate that the optimization mechanism based on the expectation of being blamed would be controlled by a neural circuit centred on the right medial prefrontal cortex. These results show novel behavioural and neural mechanisms regarding how humans optimize uncertain decisions under the expectation of being blamed.     

The New Antiepileptic Drugs and Women: Efficacy, Reproductive Health, Pregnancy, and Fetal Outcome

Summary: As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues in clude gender-specific efficacy and tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs ap pear to be at risk for compromised bone health, for dis turbances in fertility, menstrual cyclicity, ovulatory func tion, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabap-entin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development pro cess had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy ex posures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential infor mation about teratogenic effects be acquired in an accept ably short time.     

Effects of context on risk taking and decision times in obsessive-compulsive disorder

Despite the fact that OCD patients show altered decision making in everyday life, few studies have investigated how patients make risky decisions and what contextual factors impact choices. We investigated cognitive context with the use of the “framing effect” task, which investigates decision making based on whether monetarily equivalent choice options are framed in terms of a potential to either lose (lose $20 out of $50) or gain (gain $30 out of $50) money. In addition, we manipulated social context by providing positive or neutral feedback on subjects’ choices. Overall, participants were risk taking for options framed in terms of potential loss and risk averse for options framed in terms of potential gain (the classic framing effect). Although OCD patients were generally more risk averse, the effect of the frame on choices did not differ significantly from healthy participants and choices were not impacted by social context. Within OCD patients, greater self-reported indecisiveness was associated with a larger effect of the frame on choices. OCD patients were also significantly slower to make choices in the loss compared to gain frame, an effect that was not observed among healthy participants. Overall, our results suggest that the framing of choice options has a differential effect on decision times but not the actual choices made by OCD patients, and that patients are not sensitive to social feedback when making choices. The correlation between indecisiveness and the framing effect in OCD suggests that further work interrogating the relationship between specific symptoms and decision making among patients may yield new insights into the disorder.     

Sexual and reproductive behaviors among persons with mental illness

For this study, 200 women and men with a major mood disorder or schizophrenia were interviewed about their sexual and reproductive behaviors. The responses of the women and men were compared with those of persons from a national health survey who were matched for age and race. Compared with women from the national survey, women with mental illness had fewer pregnancies and live births but were more likely to have had a pregnancy that did not result in a live birth. Women with mental illness had more lifetime sexual partners. The findings suggest that clinicians should pay attention to patients' sexual and reproductive health.     

Neurons in the frontal lobe encode the value of multiple decision variables

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making.     

Gender disadvantage and reproductive health risk factors for common mental disorders in women: a community survey in India

BACKGROUND: Gender disadvantage and reproductive health are major determinants of women's health in developing countries. OBJECTIVE: To determine the association of factors indicative of gender disadvantage and reproductive health with the risk of common mental disorders (CMDs) in women. DESIGN: Cross-sectional survey from November 1, 2001, to June 15, 2003. PARTICIPANTS: A total of 3000 women randomly selected from a sampling frame of women aged 18 to 45 years in Goa; 2494 women participated. MAIN OUTCOME MEASURES: The primary outcome was the presence of a CMD, as defined by the Revised Clinical Interview Schedule. An interview and blood and vaginal/urine specimens were collected to ascertain risk factors. RESULTS: The prevalence of CMD was 6.6% (95% confidence interval [CI], 5.7%-7.6%). Mixed anxiety-depressive disorder was the most common diagnosis (64.8%). Factors independently associated with the risk for CMD were factors indicative of gender disadvantage, particularly sexual violence by the husband (odds ratio [OR], 2.3; 95% CI, 1.1-4.6), being widowed or separated (OR, 5.4; 95% CI, 1.0-30.0), having low autonomy in decision making (OR, 1.98; 95% CI, 1.2-3.2), and having low levels of support from one's family (OR, 2.2; 95% CI, 1.4-3.3); reproductive health factors, particularly gynecological complaints such as vaginal discharge (OR, 3.2; 95% CI, 2.2-4.8) and dyspareunia (OR, 2.5; 95% CI, 1.4-4.6); and factors indicative of severe economic difficulties, such as hunger (OR, 2.7; 95% CI, 1.6-4.6). There was no association between biological indicators (anemia and reproductive tract infections) and CMD. CONCLUSIONS: The clinical assessment of CMD in women must include exploration of violence and gender disadvantage. Gynecological symptoms may be somatic equivalents of CMD in women in Asian cultures.     

Disorders of reproduction in patients with epilepsy: primary neurological mechanisms.

Reproductive disorders are unusually common among women and men with epilepsy. They are generally associated with and may be the consequence of reproductive endocrine disorders. Both epilepsy itself and antiepileptic drug use have been implicated in their pathophysiology. This review focuses on how temporolimbic dysfunction in epilepsy may disrupt normal neuroendocrine regulation and promote the development of reproductive endocrine disorders. The particular nature of the dysregulation may relate to the laterality and focality of the epilepsy and some hormonal changes may develop in close temporal relation to the occurrence of epileptiform discharges. In women, reproductive endocrine disorders include polycystic ovary syndrome, hypothalamic amenorrhea, functional hyperprolactinemia, and premature menopause. In men, hypogonadism may be hypogonadotropic, hypergonadotropic or related to hyperprolactinemia. The significance of these reproductive endocrine disorders is that they may contribute not only to sexual dysfunction and infertility but may also have an adverse impact on seizure control.     

Neurologic Care of Pregnant Women with Epilepsy

Summary: Epilepsy is a common neurologic condition in women of reproductive age. Although their risks are greater than those for women in the general population, the majority of women with epilepsy have a good pregnancy outcome. An understanding of the risks and appropriate management of both the pregnancy and epilepsy in these patients is essential for their physicians. Health-care providers should discuss contraception and reproductive issues with all of their female patients with epilepsy as they enter reproductive age. Optimal care requires prepregnancy counseling, including information about contraception, dietary folate supplementation, and the risks related to pregnancy. Although antiepileptic drugs (AEDs) have been implicated as the major cause of teratogenesis in infants born to mothers with epilepsy, uncontrolled epilepsy is also associated with maternal and fetal risk. Therefore, optimal seizure control during pregnancy remains an important goal for women with epilepsy. Women with epilepsy should be counseled about breast-feeding their infants and supported in their decision. The recommendations in this article reflect those of a Practice Parameter developed by the American Academy of Neurology Quality Standards Subcommittee.     

Temporal discounting for self and friends in adolescence: A fMRI study

Adolescence is characterized by impulsivity but also by increased importance of friendships. This study took the novel perspective of testing temporal discounting in a fMRI task where choices could affect outcomes for 96 adolescents (aged 10–20-years) themselves and their best friend. Decisions either benefitted themselves (i.e., the Self Immediate – Self Delay’ condition) or their friend (i.e., ‘Friend Immediate – Friend Delay’ condition); or juxtaposed rewards for themselves and their friends (i.e., the ‘Self Immediate – Friend Delay’ or ‘Friend Immediate – Self Delay’ conditions). We observed that younger adolescents were more impulsive; and all participants were more impulsive when this was associated with an immediate benefit for friends. Individual differences analyses revealed increased activity in the subgenual anterior cingulate cortex extending in the ventral striatum for immediate relative to delayed reward choices for self. Temporal choices were associated with activity in the prefrontal cortex, parietal cortex, insula, and ventral striatum, but only activity in the right inferior parietal lobe was associated with age. Finally, temporal delay choices for friends relative to self were associated with increased activity in the temporo-parietal junction and precuneus. Overall, this study shows a unique role of the social context in adolescents’ temporal decision making.     

Impact of ambiguity and risk on decision making in mild Alzheimer's disease

Decisions under ambiguity and decisions under risk are crucial types of decision making in daily living at any age. This is the first study assessing these two types of decisions in patients with mild dementia of Alzheimer's type (DAT) by means of the Iowa Gambling Task (IGT) and a newly developed, Probability-Associated Gambling (PAG) task. While rules for gains and losses are implicit in the IGT, in the PAG task rules are explicit and winning probabilities, which change from trial to trial, can be estimated. Results of the IGT indicated that DAT patients made more disadvantageous decisions than healthy controls. Patients also shifted more frequently among decks, i.e. under ambiguity decisions were taken randomly and no advantageous strategy was established over time by DAT patients. Thus, not only actual choices but also development of advantageous strategies may be revealing about decision making in the IGT. Compared to controls, patients demonstrated less advantageous choices in the PAG task as well. They gambled more often in the low winning probabilities and less frequently in the high probabilities than healthy participants. Patients' performance on both tasks correlated with measures of executive functions. Findings of the present investigation are consistent with the early pathological cerebral changes and related (cognitive, emotional) deficits reported for DAT. As suggested by our study, decisions under ambiguity as well as decisions under risk are impaired in mild DAT. It may thus be expected that patients with mild DAT have difficulties in taking decisions in every-day life situations, both in cases of ambiguity (information on probability is missing or conflicting, and the expected utility of the different options is incalculable) and in cases of risk (outcomes can be predicted by well-defined or estimable probabilities).     

An objective measure of reinforcement and its implications for exercise promotion in sedentary Hispanic and Anglo women

An objective measure for the assessment of exercise and sedentary activity choices was evaluated for reliability in 38 sedentary women, aged 18-45, in El Paso, TX. Twenty-two Hispanic women and 16 Anglo women participated. An equal number of obese and nonobese women comprised each group of participants. Using five computer-generated slot machine games, participants were allowed to earn points for access to a bicycle/stair stepper or videos/magazines. Exercise alternatives remained easily accessible while the sedentary choices became progressively difficult to access. Two sessions were completed at least 2 weeks apart for reliability. Reliability for choosing to be physically active from session to session was rI = .83 for all participants, rI = .90 for Hispanics, and rI = .74 for Anglos. Hispanic women earned twice the number of points for access to exercise (m = 20 +/- 2; 40% of the available points) as Anglo women (m = 10 +/- 3; 20% of the available points), independent of body mass index (BMI) or socioeconomic status (SES). Hispanic women's choices to exercise were independent of acculturation level; however, Hispanic women of higher SES and lower BMI chose to exercise more than Hispanic women of lower SES and higher BMI. Hispanic women may find exercise more reinforcing than Anglo women, which has important implications for exercise interventions. In addition, results indicated that self-reported liking and enjoyment of exercise were not related to the choice to actually engage in exercise. The behavioral economic methods presented in this study provide preliminary results to support the use of an objective, reliable method to assess the determinants of exercise and sedentary activity choices in sedentary, Hispanic and Anglo women.     

Spirituality and treatment choices by South and East Asian women with serious mental illness

The purpose of this qualitative study is to investigate how South and East Asian immigrant women who have diagnoses of serious mental illness make treatment choices in relation to spirituality and to explore how gender, cultural beliefs, and spirituality intersect with the process of choice. The findings reveal that the process of spiritual choice includes three interrelated phases: (1) identifying contributing factors, (2) exploring spiritual resources and strategies, and (3) living with the choices. Variations among health beliefs and health care decisions are explained and services that women see as being helpful are identified.     

Orgasm-induced prolactin secretion: feedback control of sexual drive?

Recent studies from our laboratory have investigated the hormonal response to various forms of sexual stimulation, including film, masturbation, and coitus in both men and women. This series of studies clearly demonstrated that plasma prolactin (PRL) concentrations are substantially increased for over 1h following orgasm (masturbation and coitus conditions) in both men and women, but unchanged following sexual arousal without orgasm. Here we discuss evidence suggesting that the PRL response to orgasm may play an important role in the control of acute sexual arousal following orgasm. Supporting this position, chronic elevations of PRL (hyperprolactinemia) produce pronounced reductions in animal sexual activity, and significant reduction of libido and gonadal function in both men and women. These data suggest that PRL may represent a peripheral regulatory factor for reproductive function, and/or a feedback mechanism that signals CNS centres controlling sexual arousal and behaviour. Thus, we propose a theoretical model of the role of PRL as a neuroendocrine reproductive reflex.     

Effects of transcranial direct current stimulation on risky decision making are mediated by ‘hot’ and ‘cold’ decisions,personality, and hemisphere

Previous results point towards a lateralization of dorsolateral prefrontal cortex (DLPFC) function in risky decision making. While the right hemisphere seems involved in inhibitory cognitive control of affective impulses, the left DLPFC is crucial in the deliberative processing of information relevant for the decision. However, a lack of empirical evidence precludes definitive conclusions. The aim of our study was to determine whether anodal transcranial direct current stimulation (tDCS) over the right DLPFC with cathodal tDCS over the lDLPFC (anodal right/cathodal left) or vice versa (anodal left/cathodal right) differentially modulates risk‐taking in a task [the Columbia Card Task (CCT)] specifically engaging affect‐charged (Hot CCT) vs. deliberative (Cold CCT) decision making. The facilitating effect of the anodal stimulation on neuronal activity was emphasized by the use of a small anode and a big cathode. To investigate the role of individual differences in risk‐taking, participants were either smokers or non‐smokers. Anodal left/cathodal right stimulation decreased risk‐taking in the ‘cold’ cognition version of the task, in both groups, probably by modulating deliberative processing. In the ‘hot’ version, anodal right/cathodal left stimulation led to opposite effects in smokers and non‐smokers, which might be explained by the engagement of the same inhibitory control mechanism: in smokers, improved controllability of risk‐seeking impulsivity led to more conservative decisions, while inhibition of risk‐aversion in non‐smokers resulted in riskier choices. These results provide evidence for a hemispheric asymmetry and personality‐dependent tDCS effects in risky decision making, and may be important for clinical research on addiction and depression.     

Cefalea: embarazo y lactancia. Recomendaciones del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología (GECSEN)

IntroductionHeadache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Grouphas prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding.DevelopmentThis guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding.ConclusionsWe hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients.