"We Followed their Lead": Exploring Relational Change and Support among Caregivers of Transgender and Gender Diverse Youth.

Transgender and gender diverse youth and young adults (TGDY) experience higher mental health morbidity, including self-harm, suicide ideation, and suicide attempts, as compared to cisgender peers. Support from family members is associated with improved mental health outcomes for TGDY. However, little is known about the process that caregivers who consider themselves supportive undergo and how caregiver-youth relationships evolve through a TGDY's gender journey. Through a reflexive thematic analysis of 14 interviews conducted with caregivers of TGDY from April-July 2022, we sought to understand how caregivers who considered themselves supportive of TGDY navigated shifting relationships with themselves, their children, and their communities. Applying theories of Ambiguous Loss and Thriving Through Relationships, findings coalesced around several themes including reflecting on change, re-negotiating interpersonal relationships, and educating through relationships. The gender journeys of TGDY required caregivers to navigate relationships with self (feeling loss and wrestling with worry for their child), negotiate relationships with others (disclosing to extended family and social networks), and educate themselves and others through relationships (connecting through personal narratives from other families, parents supporting parents, learning to advocate for their child). The process of caregivers learning to support their children was facilitated through profound intrapersonal and interpersonal reflection, connection, and community. Understanding this process is important to inform educational interventions and programs that help caregivers learn to support and advocate effectively for TGDY.

Global health reciprocal innovation to address mental health and well-being: strategies used and lessons learnt.

Over the past two decades there have been major advances in the development of interventions promoting mental health and well-being in low- and middle-income countries (LMIC), including delivery of care by non-specialist providers, incorporation of mobile technologies and development of multilevel community-based interventions. Growing inequities in mental health have led to calls to adopt similar strategies in high-income countries (HIC), learning from LMIC. To overcome shared challenges, it is crucial for projects implementing these strategies in different global settings to learn from one another. Our objective was to examine cases in which mental health and well-being interventions originating in or conceived for LMIC were implemented in the USA. The cases included delivery of psychological interventions by non-specialists, HIV-related stigma reduction programmes, substance use mitigation strategies and interventions to promote parenting skills and family functioning. We summarise commonly used strategies, barriers, benefits and lessons learnt for the transfer of these innovative practices among LMIC and HIC. Common strategies included intervention delivery by non-specialists and use of digital modalities to facilitate training and increase reach. Common barriers included lack of reimbursement mechanisms for care delivered by non-specialists and resistance from professional societies. Despite US investigators' involvement in most of the original research in LMIC, only a few cases directly involved LMIC researchers in US implementation. In order to achieve greater equity in global mental health and well-being, more efforts and targeted funding are needed to develop best practices for global health reciprocal innovation and iterative learning in HIC and LMIC.

Dissociating the effect of flavor and nicotine in smokeless tobacco products using electroencephalography: The case of wintergreen flavors.

The increased consumption of tobacco products in recent years has been linked, among other factors, to the presence of added flavors. Although flavors are important in explaining consumption, their effects in the brain have until now been unexplored. In the present study, we investigated how electrophysiology can serve to dissociate the effects of nicotine and flavor. Participants attended 4 sessions (2-by-2 factorial design, with flavor and nicotine as within-subject factors), in each session an oddball task was performed before and after smokeless tobacco consumption. We explored the dissociation of neural responses to flavor and nicotine. While event-related potentials did not show modulation due to flavors, time-frequency showed a flavor-nicotine dissociation. Low-frequency activity (delta, theta and alpha) showed only effects of nicotine, and high-frequency activity (beta1, beta2 and gamma) showed effects only susceptible to flavor. Flavors in smokeless tobacco not only made the product more desirable but also triggered the allocation of cognitive resources. This long-lasting effect of flavor may enhance the addictive potential of the tobacco product. Further research is being developed to determine the precise role of flavors in contributing to addiction. This is the first study investigating the neural effects of flavor (specifically wintergreen) in smokeless tobacco products. By understanding the effects of flavors in the brain we can explain the precipitants of tobacco consumption behaviors, and the addictive potential of flavors. Regulators will be able to determine if and in which amount flavors should be allowed in tobacco products.

A dual process perspective on advances in cognitive science and alcohol use disorder.

There is a tremendous global and national (US) burden associated with alcohol misuse and alcohol use disorder (AUD). Further, of the mental health disorders, AUD has the widest treatment gap. Thus, there is a critical need for improved understanding of the etiology, maintenance, and treatment of AUD. The application of cognitive science to the study of AUD has a longstanding history of attempting to meet this need. In this selective review, we identified and focused on four domains of recent (i.e., in the last decade) applications of cognitive science to the study of AUD: implicit cognitive biases, executive function, behavioral economic approaches to alcohol decision making, and functional connectivity neuroimaging. We highlighted advances within these four domains and considered them in the context of dual process models of addiction, which focus on the contribution and interplay of two complementary neurocognitive systems (impulsive and control systems). Findings across the domains were generally consistent with dual process models. They also suggest the need for further model refinements, including integrating behavioral economic approaches and findings from functional connectivity neuroimaging studies. Research evaluating candidate interventions associated with these domains is emergent but promising, suggesting important directions for future research.

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

Neurotransmitters and Novelty: A Systematic Review.

Our brains are highly responsive to novelty. However, how novelty is processed in the brain, and what neurotransmitter systems play a role therein, remains elusive. Here, we systematically review studies on human participants that have looked at the neuromodulatory basis of novelty detection and processing. While theoretical models and studies on nonhuman animals have pointed to a role of the dopaminergic, cholinergic, noradrenergic and serotonergic systems, the human literature has focused almost exclusively on the first two. Dopamine was found to affect electrophysiological responses to novelty early in time after stimulus presentation, but evidence on its effects on later processing was found to be contradictory: While neuropharmacological studies mostly yielded null effects, gene studies did point to an important role for dopamine. Acetylcholine seems to dampen novelty signals in the medial temporal lobe, but boost them in frontal cortex. Findings on 5-HT (serotonin) were found to be mostly contradictory. Two large gaps were identified in the literature. First, few studies have looked at neuromodulatory influences on behavioral effects of novelty. Second, no study has looked at the involvement of the noradrenergic system in novelty processing.

Happier, faster: Developmental changes in the effects of mood and novelty on responses.

Positive mood ameliorates several cognitive processes: It can enhance cognitive control, increase flexibility, and promote variety seeking in decision making. These effects of positive mood have been suggested to depend on frontostriatal dopamine, which is also associated with the detection of novelty. This suggests that positive mood could also affect novelty detection. In the present study, children and adults saw either a happy or a neutral movie to induce a positive or neutral mood. After that, they were shown novel and familiar images. On some trials a beep was presented over headphones either at the same time as the image or at a 200-ms stimulus onset asynchrony (SOA), and the task of the participant was to detect these auditory targets. Children were slower in responding than adults. Positive mood, however, speeded responses, especially in children, and induced facilitatory effects of novelty. These effects were consistent with increased arousal. Although effects of novelty were more consistent with an attentional response, in children who had watched a happy movie the novel images evoked a more liberal response criterion, suggestive of increased arousal. This suggests that mood and novelty may affect response behaviour stronger in children than in adults.

Novelty's effect on memory encoding.

It is often thought that novelty benefits memory formation. However, support for this idea mostly comes from paradigms that are open to alternative explanations. In the present study we manipulated novelty in a word-learning task through task-irrelevant background images. These background images were either standard (presented repeatedly), or novel (presented only once). Two types of background images were used: Landscape pictures and fractals. EEG was also recorded during encoding. Contrary to the idea that novelty aids memory formation, memory performance was not affected by the novelty of the background. In the evoked response potentials, we found evidence of distracting effects of novelty: both the N1 and P3b components were smaller to words studied with novel backgrounds, and the amplitude of the N2b component correlated negatively with subsequent retrieval. We conclude that although evidence from other studies does suggest benefits on a longer time scale, novelty has no instantaneous benefits for learning.

How to stop or change a motor response: Laplacian and independent component analysis approach.

Response inhibition is an essential control function necessary to adapt one's behavior. This key cognitive capacity is assumed to be dependent on the prefrontal cortex and basal ganglia. It is unresolved whether varying inhibitory demands engage different control mechanisms or whether a single motor inhibitory mechanism is involved in any situation. We addressed this question by comparing electrophysiological activity in conditions that require stopping a response to conditions that require switching to an alternate response. Analyses of electrophysiological data obtained from stop-signal tasks are complicated by overlapping stimulus-related activity that is distributed over frontal and parietal cortical recording sites. Here, we applied Laplacian transformation and independent component analysis (ICA) to overcome these difficulties. Participants were faster in switching compared to stopping a response, but we did not observe differences in neural activity between these conditions. Both stop- and change-trials Laplacian transformed ERPs revealed a comparable bilateral parieto-occipital negativity around 180 ms and a frontocentral negativity around 220 ms. ICA results suggested an inhibition-related frontocentral component which was characterized by a negativity around 200 ms with a likely source in anterior cingulate cortex. The data provide support for the importance of posterior mediofrontal areas in inhibitory response control and are consistent with a common neural pathway underlying stopping and changing of a motor response. The methodological approach proved useful to distinguish frontal and parietal sources despite similar timing and the ICA approach allowed assessment of single-trial data with respect to behavioral data.

The detection of novelty relies on dopaminergic signaling: evidence from apomorphine's impact on the novelty N2.

Despite much research, it remains unclear if dopamine is directly involved in novelty detection or plays a role in orchestrating the subsequent cognitive response. This ambiguity stems in part from a reliance on experimental designs where novelty is manipulated and dopaminergic activity is subsequently observed. Here we adopt the alternative approach: we manipulate dopamine activity using apomorphine (D1/D2 agonist) and measure the change in neurological indices of novelty processing. In separate drug and placebo sessions, participants completed a von Restorff task. Apomorphine speeded and potentiated the novelty-elicited N2, an Event-Related Potential (ERP) component thought to index early aspects of novelty detection, and caused novel-font words to be better recalled. Apomorphine also decreased the amplitude of the novelty-P3a. An increase in D1/D2 receptor activation thus appears to potentiate neural sensitivity to novel stimuli, causing this content to be better encoded.

Electrophysiological analysis of the role of novelty in the von Restorff effect.

Items that are distinctive with respect to their context tend to be recalled better than nondistinctive items, a finding known as the von Restorff effect. The goal of this study was to elucidate the role of novelty in this effect. In two experiments, participants performed a dual task in which they had to study words presented visually while to-be ignored sounds were played over earphones. Sounds could be either standard or novel, and words could be presented in standard or novel font. Sounds were presented either simultaneously with the words (Experiment 1) or preceding them (Experiment 2). Electrophysiological correlates of novelty processing, the N2b and P3a ERP components, were recorded while the words were studied. It was seen that cued recall was better for words presented in novel fonts than for words in a standard font (the von Restorff effect). Words presented while novel sounds were played were remembered worse (Experiment 1) or equally well (Experiment 2) than those combined with standard sounds. Words presented in novel fonts elicited enhanced N2b, P3a, P3b, and N400 components; however, none of these components were specifically larger for subsequently recalled novel-font words. A larger N2b was found for recalled than for nonrecalled words, but this effect was not specific for words presented in novel font. We hypothesized that if novelty was beneficial for memory processing, the N2-P3 complex would be more enhanced for novel words that were later recalled than for those not recalled. The data showed otherwise. This suggests that novelty processing, as indexed by the N2-P3 novelty components, is not the main cause of the von Restorff effect.