Responses In Prefrontal Cortex Research Articles

Neural responses to morally laden interactions in female inmates with psychopathy

Much of social cognition requires making inferences about the mental and emotional states of others. Moreover, understanding the emotions of others is an important foundation for moral decision-making. Psychopathy is associated with both aberrant emotional understanding and atypical hemodynamic responses when viewing and evaluating morally laden social interactions. In the present functional MRI study, female inmates (N = 107) were asked to evaluate the likely emotional state of either the recipient or the initiator of harmful or helpful interactions. Psychopathy was assessed with the Psychopathy Checklist-Revised (PCL-R). PCL-R scores were not associated with differences in confidence or accuracy ratings. However, psychopathy scores were significantly related to increased hemodynamic response in right dorsolateral prefrontal cortex when viewing harmful interactions and decreased functional connectivity from right amygdala to inferior parietal cortex and insula, and from temporal parietal junction to dorsomedial prefrontal cortex. Overall, this work indicates that in females, psychopathy is associated with normal behavioral accuracy and confidence but alterations in neural network activity during moral decision-making.

Diminished prefrontal cortex activation in patients with binge eating disorder associates with trait impulsivity and improves after impulsivity-focused treatment based on a randomized controlled IMPULS trial

BackgroundBehavioral and cognitive control are vital for healthy eating behavior. Patients with binge eating disorder (BED) suffer under recurrent binge eating episodes accompanied by subjective loss of control that results, among other factors, from increased impulsivity. MethodsIn the current study, we investigated the frontal network using functional near-infrared spectroscopy (fNIRS) during a food specific go/nogo task to assess response inhibition in 24 patients with BED (BMI range 22.6–59.7 kg/m2) compared to 12 healthy controls (HC) (BMI range 20.9–27 kg/m2). Patients with BED were invited to undergo fNIRS measurements before an impulsivity-focused cognitive behavioral group treatment, directly after this treatment and 3 months afterwards. As this was a planned subgroup analysis of the randomized controlled IMPULS trial, patients with BED were randomized either to the treatment group (n = 14) or to a control group (n = 10). The treatment group received 8 weekly sessions of the IMPULS treatment. ResultsWe found a significant response inhibition effect (nogo minus go), in terms of an increased oxygenated hemoglobin response in the bilateral prefrontal cortex in both groups. The greatest response was observed when participants were instructed to go for healthy and withhold their response to unhealthy high caloric food cues. The healthy nogo condition failed to show a significant prefrontal inhibitory response, which was probably related to the task design, as the condition was considered more demanding. BED patients, especially those with higher trait impulsivity, showed a weaker activation of the prefrontal cortex during response inhibition, predominantly in the right hemisphere. Interestingly, three months after the treatment, patients of the treatment group increased their right prefrontal cortex activity during response inhibition. Likewise, increased prefrontal cortex activation correlated with decreased trait impulsivity after treatment. ConclusionsOur results suggest that patients with BED have limited resources to activate the prefrontal cortex when asked to inhibit a reaction onto food-specific stimuli. However, this effect could be partly driven by differences in BMI between the HC and BED group. Cognitive-behavioral therapy targeting impulsive eating behavior may improve prefrontal cortex recruitment during response inhibition.

Evidence of fNIRS-Based Prefrontal Cortex Hypoactivity in Obesity and Binge-Eating Disorder.

Obesity (OB) and associated binge-eating disorder (BED) show increased impulsivity and emotional dysregulation. Albeit well-established in neuropsychiatric research, functional near-infrared spectroscopy (fNIRS) has rarely been used to study OB and BED. Here, we investigated fNIRS-based food-specific brain signalling, its association with impulsivity and emotional dysregulation, and the temporal variability in individuals with OB with and without BED compared to an age- and sex-stratified normal weight (NW) group. Prefrontal cortex (PFC) responses were recorded in individuals with OB (n = 15), OB + BED (n = 13), and NW (n = 12) in a passive viewing and a response inhibition task. Impulsivity and emotional dysregulation were self-reported; anthropometrics were objectively measured. The OB and NW groups were measured twice 7 days apart. Relative to the NW group, the OB and OB + BED groups showed PFC hyporesponsivity across tasks, whereas there were few significant differences between the OB and OB + BED groups. Greater levels of impulsivity were significantly associated with stronger PFC responses, while more emotional dysregulation was significantly associated with lower PFC responses. Temporal differences were found in the left orbitofrontal cortex responses, yet in opposite directions in the OB and NW groups. This study demonstrated diminished fNIRS-based PFC responses across OB phenotypes relative to a NW group. The association between impulsivity, emotional dysregulation, and PFC hypoactivity supports the assumption that BED constitutes a specific OB phenotype.

Neural Substrates of Food Valuation and Its Relationship With BMI and Healthy Eating in Higher BMI Individuals.

Considerable evidence points to a link between body mass index (BMI), eating behavior, and the brain's reward system. However, much of this research focuses on food cue reactivity without examining the subjective valuation process as a potential mechanism driving individual differences in BMI and eating behavior. The current pre-registered study (https://osf.io/n4c95/) examined the relationship between BMI, healthy eating, and subjective valuation of healthy and unhealthy foods in a community sample of individuals with higher BMI who intended to eat more healthily. Particularly, we examined: (1) alterations in neurocognitive measures of subjective valuation related to BMI and healthy eating; (2) differences in the neurocognitive valuation for healthy and unhealthy foods and their relation to BMI and healthy eating; (3) and whether we could conceptually replicate prior findings demonstrating differences in neural reactivity to palatable vs. plain foods. To this end, we scanned 105 participants with BMIs ranging from 23 to 42 using fMRI during a willingness-to-pay task that quantifies trial-by-trial valuation of 30 healthy and 30 unhealthy food items. We measured out of lab eating behavior via the Automated Self-Administered 24 H Dietary Assessment Tool, which allowed us to calculate a Healthy Eating Index (HEI). We found that our sample exhibited robust, positive linear relationships between self-reported value and neural responses in regions previously implicated in studies of subjective value, suggesting an intact valuation system. However, we found no relationship between valuation and BMI nor HEI, with Bayes Factor indicating moderate evidence for a null relationship. Separating the food types revealed that healthy eating, as measured by the HEI, was inversely related to subjective valuation of unhealthy foods. Imaging data further revealed a stronger linkage between valuation of healthy (compared to unhealthy) foods and corresponding response in the ventromedial prefrontal cortex (vmPFC), and that the interaction between healthy and unhealthy food valuation in this region is related to HEI. Finally, our results did not replicate reactivity differences demonstrated in prior work, likely due to differences in the mapping between food healthiness and palatability. Together, our findings point to disruptions in the valuation of unhealthy foods in the vmPFC as a potential mechanism influencing healthy eating.

The Modulatory Role of Cortisol in the Regulation of Sexual Behavior in Young Males

The proneness to be sexually aroused, to perform sexual acts, or to be sexually disinhibited during a particular mood varies across individuals. However, the physiological mechanisms underlying this specific and variable relationship between mood and sex-related processes are poorly understood. We propose that cortisol may act as an important moderator in this as it has shown to influence sexual arousal and to play a neuromodulatory role during emotion regulation. Here, we conducted a functional magnetic resonance imaging study in a sample of young males to investigate whether cortisol modulates the neural response during the approach of sexual stimuli in an approach-avoidance task and whether this potential relationship explains the individual differences in sexual inhibition and in mood-related sexual interest and activity. We revealed that cortisol associates with the anteromedial prefrontal cortex activation during the approach towards sexual stimuli. Moreover, this anteromedial prefrontal cortex response was dependent on individual differences in sexual inhibition and the improvements of negative mood as a result of sexual activity. The anteromedial prefrontal cortex is already known to process bottom-up information, reward, and risk estimation. The neuromodulatory role of cortisol within this region during sexual approach may represent a previously unknown yet key element in the regulation of sexual behavior in young males.

P.069 Effects of vortioxetine and agomelatine in the Differential Reinforcement of Low Rate (DRL) test in the rat

Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD.We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene.While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortexSimilar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD.

Differing functional mechanisms underlie cognitive control deficits in psychotic spectrum disorders.

Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response. Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization. Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control. In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired. Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.

Altered prefrontal cortex responses in older adults with subjective memory complaints and dementia during dual-task gait: An fNIRS study.

People with cognitive impairments show deficits during physical performances such as gait, in particular during cognitively challenging conditions (i.e. dual-task gait [DTG]). However, it is unclear if people at risk of dementia, such as those with subjective memory complaints (SMC), also display gait and central deficits associated with DTG. In this study, we investigated the effects of single- and dual-task gait (STG and DTG), on left prefrontal cortex (PFC) activation in elderly people with subjective memory complaints (SMC) and Dementia. A total of 58 older adults (aged 65-94years; 26 Healthy; 23 SMC; 9 Dementia) were recruited. Gait spatiotemporal characteristics (i.e. stride velocity and length) were assessed using an instrumented walkway during STG and DTG. Single-channel functional near-infrared spectroscopy over the left PFC was used to measure changes in oxyhaemoglobin (O2 Hb) during gait. Stride velocity and length during STG (all p<.05) and DTG (all p<.000) were significantly impaired in people with Dementia compared to Healthy and SMC individuals. No differences were observed between Healthy and SMC. For STG, a greater increase in O2 Hb (p<.05) was observed in those with Dementia compared to the Healthy and SMC, while no differences were observed between Healthy and SMC. A significant increase and decline in O2 Hb was observed during DTG in the SMC and Dementia groups, respectively, compared to Healthy. Our findings indicate an altered pattern of cerebral haemodynamic response of the left PFC in DTG in people with SMC and Dementia, which may suggest that central changes precede functional impairments in people with SMC.

Prefrontal Cortex Response to Threat: Race by Age Variation in 9-10 Year Old Children.

Considerable research has suggested that race and age are two major determinants of brain development, including but not limited to development of the prefrontal cortex (PFC). Minorities' Diminished Returns (MDRs), however, suggests that race (as a proxy of racism) may interact with various determinants of human and brain development. Minimal knowledge, however, exists on whether age and race also interact on shaping PFC response to threat among American children. Using data from a task-based functional brain imaging study and considering race as a sociological rather than a biological construct, we investigated combined effects of race and age on prefrontal cortical (PFC) response to threat. We explored racial heterogeneities in the association between age and PFC response to threat by comparing Black and White children. This study used the task-based functional Magnetic Resonance Imaging (fMRI) data from the Adolescents Brain Cognitive Development (ABCD) study, a national, landmark, multi-center brain imaging investigation of 9-10 years old children in the US. The primary outcomes were mean beta weights of n-back runs measuring PFC response to threating versus neutral face contrast in the following regions of interest (ROIs): left hemisphere-lateral orbito-frontal, left hemisphere -superior-frontal, right hemisphere -caudal middle frontal, and right hemisphere -superior frontal cortex. The independent variable was age. Covariates were sex, ethnicity, family socioeconomic status, and neighborhood socioeconomic status. Race was the focal moderator. To analyze the data, we used linear regression models without and with interactions and SES as covariates. We included 5,066 9-10 years old children. Age and race did not show direct effects on PFC response to threatening relative to neutral faces. While ethnicity, sex, and socioeconomic status were controlled, age and race showed a systematic interaction on PFC response to threatening relative to neutral faces. For American children, race and age do not have direct effects but multiplicative effects on PFC response to threat. The results may be reflective of social inequalities in how Black and White children are socialized and developed. The results are important given the role of the PFC in regulating the limbic system response to threat. Coordinated work of the limbic system and PFC is a core element of children's behavioral and emotional development. Future research is needed on how social stratification and racism shape emotion processing and regulation of American children in response to threat.

The association of prefrontal cortex response during a natural reward cue-reactivity paradigm, anhedonia, and demoralization in persons maintained on methadone

Persons with opioid use disorder (OUD) often experience anhedonia and demoralization, yet there is relatively little research on the pathophysiology of anhedonia and demoralization in OUD treatment and recovery. In the current study, persons maintained on methadone (N = 29) underwent a natural reward-cue paradigm during functional near-infrared spectroscopy (fNIRS) imaging. Natural reward cues included highly palatable food, positive social interactions (e.g., a happy family at the dinner table), and emotional intimacy (e.g. couples embracing or kissing, but no erotic images). Participants also self-reported symptoms of anhedonia on the Snaith-Hamilton Pleasure Scale (SHPS) and demoralization on the Demoralization Scale II (DS-II). Participants who reported clinically-significant anhedonia on the SHPS displayed decreased neural activity in the right prefrontal cortex (PFC) in response to natural reward cues (F(1,25) = 3.612, p = 0.027, ηp2 = 0.302). In linear regression models of positive social cues, decreased neural activity in the right VMPFC was associated with increased SHPS total score (F(1,27) = 7.131, R2 = 0.209, p = .013), and decreased neural activity in an area encompassing the right lateral VMPFC and DLPFC was associated with increased DS-II total score (F(1,27) = 10.641, R2 = 0.283, p = 0.003). This study provides initial evidence that the prefrontal cortex is involved in the pathophysiology of anhedonia and demoralization in persons in recovery from OUD. Anhedonia and demoralization are important treatment outcomes that should be queried along with a constellation of physical and mental health outcomes, to assess areas of needed improvement in methadone maintenance and other OUD treatment modalities.

Dysfunction of the Prefrontal Cortex in Betel-Quid-Dependent Chewers.

Betel quid is the fourth most popular psychoactive agent worldwide. Imaging studies have found altered brain structure in prefrontal cortex (PFC) in betel-quid dependent (BQD) chewers. However, the brain function in PFC associated with BQ use still remains unclear. The present study aimed to examine brain functional activity in PFC in individuals with BQD. This study recruited 48 participants with BQD and 22 normal controls (NCs). Both BQ-specific cue reactivity and Go/NoGo tasks were administered with functional magnetic resonance imaging (fMRI). Behavioral results showed a deficit in the choice reaction time task in BQD group. The fMRI results of the cue reactivity task suggested that, individuals with BQD exhibited responses in right ventromedial PFC, left posterior cingulate cortex (PCC), left lateral parietal lobe (LPL), left middle temporal gyrus and left visual cortex, when seeing BQ images compared with control images. In the Go/NoGo task, relative to NCs group, individuals with BQD showed higher activity in right dorsolateral PFC, right PCC and bilateral LPL between NoGo and Go trials. Across these two tasks, we consistently found disrupted function in PFC in individuals with BQD, which might lead to impaired craving and response inhibition in BQ addiction. Results of current study might shed light on the neural mechanisms involved in BQ use, which could be used as potential guidelines for diagnosis and treatment of BQ dependence.

Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

People with anorexia nervosa (AN) commonly exhibit social difficulties, which may be related to problems with understanding the perspectives of others, commonly known as Theory of Mind (ToM) processing. However, there is a dearth of literature investigating the neural basis of these differences in ToM and at what age they emerge. This study aimed to test for differences in the neural correlates of ToM processes in young women with AN, and young women weight-restored (WR) from AN, as compared to healthy control participants (HC). Based on previous findings in AN, we hypothesized that young women with current or prior AN, as compared to HCs, would exhibit a reduced neural response in the medial prefrontal cortex (mPFC), the inferior frontal gyrus, and the temporo-parietal junction (TPJ) whilst completing a ToM task. We recruited 73 young women with AN, 45 WR young women, and 70 young women without a history of AN to take part in the current study. Whilst undergoing a functional magnetic resonance imaging (fMRI) scan, participants completed the Frith-Happé task, which is a commonly used measure of ToM with demonstrated reliability and validity in adult populations. In this task, participants viewed the movements of triangles, which depicted either action movements, simple interactions, or complex social interactions. Viewing trials with more complex social interactions in the Frith-Happé task was associated with increased brain activation in regions including the right TPJ, the bilateral mPFC, the cerebellum, and the dorsolateral prefrontal cortex. There were no group differences in neural activation in response to the ToM contrast. Overall, these results suggest that the neural basis of spontaneous mentalizing is preserved in most young women with AN.

Potential role of primed microglia during obesity on the mesocorticolimbic circuit in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease which involves functional and structural defects in selective central nervous system (CNS) regions that harm function and individual ability to process and respond to external stimuli. Individuals with ASD spend less time engaging in social interaction compared to non-affected subjects. Studies employing structural and functional magnetic resonance imaging reported morphological and functional abnormalities in the connectivity of the mesocorticolimbic reward pathway between the nucleus accumbens and the ventral tegmental area (VTA) in response to social stimuli, as well as diminished medial prefrontal cortex in response to visual cues, whereas stronger reward system responses for the non-social realm (e.g., video games) than social rewards (e.g., approval), associated with caudate nucleus responsiveness in ASD children. Defects in the mesocorticolimbic reward pathway have been modulated in transgenic murine models using D2 dopamine receptor heterozygous (D2+/-) or dopamine transporter knockout mice, which exhibit sociability deficits and repetitive behaviors observed in ASD phenotypes. Notably, the mesocorticolimbic reward pathway is modulated by systemic and central inflammation, such as primed microglia, which occurs during obesity or maternal overnutrition. Therefore, we propose that a positive energy balance during obesity/maternal overnutrition coordinates a systemic and central inflammatory crosstalk that modulates the dopaminergic neurotransmission in selective brain areas of the mesocorticolimbic reward pathway. Here, we will describe how obesity/maternal overnutrition may prime microglia, causing abnormalities in dopamine neurotransmission of the mesocorticolimbic reward pathway, postulating a possible immune role in the development of ASD.

Negative Learning Bias in Depression Revisited: Enhanced Neural Response to Surprising Reward Across Psychiatric Disorders

BackgroundPrior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders. MethodsWe employed a transdiagnostic approach assessing a heterogeneous group of (nonpsychotic) psychiatric patients from the MIND-Set (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders) cohort with and without MDD but also with anxiety, attention-deficit/hyperactivity disorder, and/or autism (n = 66) and healthy control subjects (n = 24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional magnetic resonance imaging. ResultsIn contrast to previous studies, patients with MDD did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in the bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, attention-deficit/hyperactivity disorder, and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly that associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. ConclusionsPrefrontal enhancement may reflect compensatory working memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.

Naltrexone modulates contextual processing in depression.

Context, the information surrounding an experience, can significantly alter the meaning and the affective responses to events. Yet the biological mechanisms through which context modulate experiences are not entirely understood. Here, we hypothesized that the µ-opioid system-extensively implicated in placebo effects, a clinical phenomenon thought to rely on contextual processing-modulates the effects of contextual information on emotional attributions in patients with depression. To test this hypothesis, 20 unmedicated patients with depression completed a randomized, double-blind, placebo-controlled, crossover study of one dose of 50 mg of naltrexone, or placebo immediately before completing two sessions of the Contextual Framing fMRI task. This task captures effects of valenced contextual cues (pleasant vs. unpleasant) on emotional attribution (the rating of subtle emotional faces: fearful, neutral, or happy). Behaviorally, we found that emotional attribution was significantly moderated by the interaction between contextual cues and subtle emotional faces, such that participants' ratings of valenced faces (fearful and happy), compared to neutral, were more negative during unpleasant, compared to pleasant context cues. At a neural level, context-induced blood-oxygen-level-dependent responses in the ventromedial prefrontal cortex, the dorsal anterior cingulate, the dorsolateral prefrontal cortex, and the lateral orbitofrontal cortex, significantly moderated the effects of context on emotional attribution, and were blunted by naltrexone. Furthermore, the effects of naltrexone on emotional attribution were partially abolished in more severely depressed patients. Our results provide insights into the molecular alterations underlying context representation in patients with depression, providing pivotal early data for future treatment studies.

Chrna5 is Essential for a Rapid and Protected Response to Optogenetic Release of Endogenous Acetylcholine in Prefrontal Cortex.

Optimal attention performance requires cholinergic modulation of corticothalamic neurons in the prefrontal cortex. These pyramidal cells express specialized nicotinic acetylcholine receptors containing the α5 subunit encoded by Chrna5 Disruption of this gene impairs attention, but the advantage α5 confers on endogenous cholinergic signaling is unknown. To ascertain this underlying mechanism, we used optogenetics to stimulate cholinergic afferents in prefrontal cortex brain slices from compound-transgenic wild-type and Chrna5 knock-out mice of both sexes. These electrophysiological experiments identify that Chrna5 is critical for the rapid onset of the postsynaptic cholinergic response. Loss of α5 slows cholinergic excitation and delays its peak, and these effects are observed in two different optogenetic mouse lines. Disruption of Chrna5 does not otherwise perturb the magnitude of the response, which remains strongly mediated by nicotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors. However, when conditions are altered to promote sustained cholinergic receptor stimulation, it becomes evident that α5 also works to protect nicotinic responses against desensitization. Rescuing Chrna5 disruption thus presents the double challenge of improving the onset of nicotinic signaling without triggering desensitization. Here, we identify that an agonist for the unorthodox α-α nicotinic binding site can allosterically enhance the cholinergic pathway considered vital for attention. Treatment with NS9283 restores the rapid onset of the postsynaptic cholinergic response without triggering desensitization. Together, this work demonstrates the advantages of speed and resilience that Chrna5 confers on endogenous cholinergic signaling, defining a critical window of interest for cue detection and attentional processing.SIGNIFICANCE STATEMENT The α5 nicotinic receptor subunit (Chrna5) is important for attention, but its advantage in detecting endogenous cholinergic signals is unknown. Here, we show that α5 subunits permit rapid cholinergic responses in prefrontal cortex and protect these responses from desensitization. Our findings clarify why Chrna5 is required for optimal attentional performance under demanding conditions. To treat the deficit arising from Chrna5 disruption without triggering desensitization, we enhanced nicotinic receptor affinity using NS9283 stimulation at the unorthodox α-α nicotinic binding site. This approach successfully restored the rapid-onset kinetics of endogenous cholinergic neurotransmission. In summary, we reveal a previously unknown role of Chrna5 as well as an effective approach to compensate for genetic disruption and permit fast cholinergic excitation of prefrontal attention circuits.

Aging alters neural activity at event boundaries in the hippocampus and Posterior Medial network

Recent research has highlighted a role for the hippocampus and a Posterior Medial cortical network in signaling event boundaries. However, little is known about whether or how these neural processes change over the course of healthy aging. Here, 546 cognitively normal participants 18–88 years old viewed a short movie while brain activity was measured using fMRI. The hippocampus and regions of the Posterior Medial network show increased activity at event boundaries, but these boundary-evoked responses decrease with age. Boundary-evoked activity in the posterior hippocampus predicts performance on a separate test of memory for stories, suggesting that hippocampal activity during event segmentation may be a broad indicator of individual differences in episodic memory ability. In contrast, boundary-evoked responses in the medial prefrontal cortex and middle temporal gyrus increase across the age range. These findings suggest that aging may alter neural processes for segmenting and remembering continuous real-world experiences.

Dorsolateral prefrontal cortex response to negative tweets relates to executive functioning.

Cognitive performance can become impaired when a stimulus evokes an emotional response. Social media often elicits emotional reactions, but, despite social media's ubiquity, cognitive and neural consequences of exposure to negative online content are relatively unknown. Fifty-seven human adults (18-29years; 38 female) who identified with at least one historically-marginalized group performed a novel 'Tweet Task'. While undergoing functional magnetic resonance imaging, participants completed a spatial reasoning task before and after reading a set of actual tweets. Participants were randomly assigned to read negative, discriminatory tweets from President Trump (Negative Condition) or neutral tweets (Neutral Condition). Participants in the Negative Condition reported worsening affect and demonstrated performance interference post-tweet compared to those in the Neutral Condition. Affect post-tweet was associated with parametric reductions in left dorsolateral prefrontal cortex, which predicted variance in performance beyond elicited negative affect. Performance effects were demonstrated on an unrelated spatial reasoning task suggesting that engaging with negative, emotionally-arousing content on social media can have deleterious effects on executive functioning in non-social domains.

Me first: Neural representations of fairness during three-party interactions

One hallmark of human morality is a deep sense of fairness. People are motivated by both self-interest and a concern for the welfare of others. However, it remains unclear whether these motivations rely on similar neural computations, and the extent to which such computations influence social decision-making when self-fairness and other-fairness motivations compete. In this study, two groups of participants engaged in the role of responder in a three-party Ultimatum Game while being scanned with functional MRI (N = 32) or while undergoing high-density electroencephalography (N = 40). In both studies, participants accepted more OtherFair offers when they themselves received fair offers. Though SelfFairness was reliably decoded from scalp voltages by 170 ms, and from hemodynamic responses in right insula and dorsolateral prefrontal cortex, there was no overlap between neural representations of fairness for self and for other. Distinct neural computations and mechanisms seem to be involved when making decisions about fairness in three-party contexts, which are anchored in an egocentric, self-serving bias.

Play, but not observing play, engages rat medial prefrontal cortex.

Rats have elaborate cognitive capacities for playing Hide & Seek. Playing Hide & Seek strongly engages medial prefrontal cortex and the activity of prefrontal cortex neurons reflects the structure of the game. We wondered if prefrontal neurons would also show a mirroring of play-related neural activity. Specifically, we asked how does the activity in the rat medial prefrontal cortex differ when the animal plays itself versus when it observes others playing. Consistent with our previous work, when the animal plays itself we observed medial prefrontal cortex activity that was sharply locked to game events. Observing play, however, did not lead to a comparable activation of rat medial prefrontal cortex. Firing rates during observing play were lower than during real play. The modulation of responses in medial prefrontal cortex by game events was strong during playing Hide & Seek, but weak during observing Hide & Seek. We conclude the rat prefrontal cortex does not mirror play events under our experimental conditions.