Neural Activity In Brain Regions Research Articles

Similar cognitive characteristics between gaming disorder and other psychiatric disorders

IntroductionCognitive characteristics that differentiate normal from problematic gaming need to be identified, owing to the growing popularity of internet games and the rapid rise in mental health problems. Gaming disorder (GD) involves playing games despite their negative effects and is often related to unsuccessful attempts to reduce gaming. GD frequently results in adverse outcomes related to education, employment, and social responsibilities, thereby significantly influencing daily life.ObjectivesWe aimed to elucidate the neurocognitive features underlying GD development and preservation, and possible overlapping features between GD and other psychiatric disorders.MethodsWe performed a literature search to identify GD-related studies. We focused on two key aspects: (a) altered executive functions (EFs) and (b) gaming urge. We mainly searched the PubMed and Web of Science databases using relevant keywords. All retrieved literature were assessed for eligibility to reduce selection biases.ResultsOur preliminary review identified that GD features prominent deficits in EFs, including cognitive inflexibility, poor response inhibition, altered decision-making, and intensified susceptibility to game-related stimuli. These deficits were found to be associated with abnormal neural activity in brain regions subserving EFs and reward-based learning. Hence, excessive gaming may maladaptively suppress controlled and conscious processing, which can amplify automatic and implicit processes to develop gaming urges. In addition, many of these neuropsychological deficits have been observed in other addictions and seemingly unrelated disorders such as autism spectrum disorder (ASD). Similar EF deficits have been identified in ASD, which involve reduced cognitive flexibility and related dysfunction, including excessive attention focus, restricted interest, maladaptive reward processing, and reduced self-control. However, there is considerable variation among individuals and study methods, which requires more comprehensive research strategies.ConclusionsWe elucidated comparable cognitive features among individuals with GD, addiction disorders, and ASD. These similarities provide clues regarding GD etiology, ideas for improving preventative therapies, and markers for risk evaluation. Additional investigations on how GD and other disorders possess similar and distinctive cognitive functions are worth pursuing. It is also crucial to further examine the extent of shared cognitive features in the general population, wherein the peripheral pathological characteristics lie on a continuum with typical and atypical populations.Disclosure of InterestNone Declared

Investigating the different mechanisms in related neural activities: a focus on auditory perception and imagery.

Neuroimaging studies have shown that the neural representation of imagery is closely related to the perception modality; however, the undeniable different experiences between perception and imagery indicate that there are obvious neural mechanism differences between them, which cannot be explained by the simple theory that imagery is a form of weak perception. Considering the importance of functional integration of brain regions in neural activities, we conducted correlation analysis of neural activity in brain regions jointly activated by auditory imagery and perception, and then brain functional connectivity (FC) networks were obtained with a consistent structure. However, the connection values between the areas in the superior temporal gyrus and the right precentral cortex were significantly higher in auditory perception than in the imagery modality. In addition, the modality decoding based on FC patterns showed that the FC network of auditory imagery and perception can be significantly distinguishable. Subsequently, voxel-level FC analysis further verified the distribution regions of voxels with significant connectivity differences between the 2 modalities. This study complemented the correlation and difference between auditory imagery and perception in terms of brain information interaction, and it provided a new perspective for investigating the neural mechanisms of different modal information representations.

Alterations of spontaneous brain activity in type 2 diabetes mellitus without mild cognitive impairment: a resting-state functional magnetic resonance study.

Type 2 diabetes mellitus (T2DM) has been demonstrated an increased risk factor of cognitive impairment or even dementia. Kinds of resting-state functional magnetic resonance imaging indices have been proposed and used to investigate the brain mechanism underlying diabetic cognitive impairment. This study aimed to explore the early changes in spontaneous neural activity among T2DM patients without cognitive impairment by means of multiple rs-fMRI indices. T2DM patients without cognitive impairment and age-, sex-, and education matched control subjects were included in this study. Three rs-fMRI indices, namely amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC) were computed after image pre-processing. The Montreal Cognitive Assessment (MoCA) was performed to distinguish normal cognition. Brain volume was also evaluated. Correlation analyses were conducted to explore any relationship among rs-fMRI indices and clinical characteristics. The T2DM patients were detected significantly decreased neural activity in right angular and left prefrontal gyrus including middle and superior frontal gyrus. Increased activities were also observed in left caudate and the supplementary motor area. No correlation between rs-fMRI indices and clinical characteristics was survived after multiple comparison correction. But we observed a significant, but decreased correlation between ALFF and ReHo values in the reported brain areas. The combination of ALFF, ReHo and VMHC analyses demonstrated abnormal spontaneous neural activity in brain regions which were reported in T2DM patients without cognitive impairment. These results may enhance our understanding of the diabetic brain changes at the early stage.

Context-dependent activation of a social behavior brain network during learned vocal production.

Neural activation in brain regions for vocal control is social context dependent. This context-dependent brain activation reflects social context-appropriate vocal behavior but has unresolved mechanisms. Studies of non-vocal social behaviors in multiple organisms suggest a functional role for several evolutionarily conserved and highly interconnected brain regions. Here, we use neural activity-dependent gene expression to evaluate the functional connectivity of this social behavior network within zebra finches in non-social and social singing contexts. We found that activity in one social behavior network region, the medial preoptic area (POM), was strongly associated with the amount of non-social undirected singing in zebra finches. In addition, in all regions of the social behavior network and the paraventricular nucleus (PVN), a higher percentage of EGR1 expression was observed during a social female-directed singing context compared to a non-social undirected singing context. Furthermore, we observed distinct patterns of significantly correlated activity between regions of the social behavior network during non-social undirected and social female-directed singing. Our results suggest that non-social vs. social contexts differentially activate this social behavior network and PVN. Moreover, neuronal activity within this social behavior network, PVN, and POM may alter context-appropriate vocal production.

Eye movements decrease during effortful speech listening.

Hearing impairment affects many older adults but is often diagnosed decades after speech comprehension in noisy situations has become effortful. Accurate assessment of listening effort may thus help diagnose hearing impairment earlier. However, pupillometry - the most used approach to assess listening effort - has limitations that hinder its use in practice. The current study explores a novel way to assess listening effort through eye movements. Building on cognitive and neurophysiological work, we examine the hypothesis that eye movements decrease when speech listening becomes challenging. In three experiments with human participants from both sexes, we demonstrate, consistent with this hypothesis, that fixation duration increases and spatial gaze dispersion decreases with increasing speech masking. Eye movements decreased during effortful speech listening for different visual scenes (free viewing; object tracking) and speech materials (simple sentences; naturalistic stories). In contrast, pupillometry was less sensitive to speech masking during story listening, suggesting pupillometric measures may not be as effective for the assessments of listening effort in naturalistic speech-listening paradigms. Our results reveal a critical link between eye movements and cognitive load, suggesting that neural activity in the brain regions that support the regulation of eye movements, such as frontal eye field and superior colliculus, are modulated when listening is effortful.Significance statementAssessment of listening effort is critical for early diagnosis of age-related hearing loss. Pupillometry is most used but has several disadvantages. The current study explores a novel way to assess listening effort through eye movements. We examine the hypothesis that eye movements decrease when speech listening becomes effortful. We demonstrate, consistent with this hypothesis, that fixation duration increases and gaze dispersion decreases with increasing speech masking. Eye movements decreased during effortful speech listening for different visual scenes (free viewing; object tracking) and speech materials (sentences; naturalistic stories). Our results reveal a critical link between eye movements and cognitive load, suggesting that neural activity in brain regions that support the regulation of eye movements are modulated when listening is effortful.

Tracing development of song memory with fMRI in zebra finches after a second tutoring experience

Sensory experiences in early development shape higher cognitive functions such as language acquisition in humans and song learning in birds. Zebra finches (Taeniopygia guttata) sequentially exposed to two different song ‘tutors’ during the sensitive period in development are able to learn from their second tutor and eventually imitate aspects of his song, but the neural substrate involved in learning a second song is unknown. We used fMRI to examine neural activity associated with learning two songs sequentially. We found that acquisition of a second song changes lateralization of the auditory midbrain. Interestingly, activity in the caudolateral Nidopallium (NCL), a region adjacent to the secondary auditory cortex, was related to the fidelity of second-song imitation. These findings demonstrate that experience with a second tutor can permanently alter neural activity in brain regions involved in auditory perception and song learning.

Right superior frontal involved in distracted driving

Electroencephalogram (EEG) was used to analyze the differences in brain area activation correlations between driving distraction (visual distraction, auditory distraction, and cognitive distraction) and normal driving. Thirty subjects participated in this study. Three subtasks were designed, which occurred randomly during driving simulation, to investigate the effects of different distractions on the drivers' neural activity. The drivers' right intraorbital superior frontal gyrus and right infraorbital frontal gyrus were significantly activated during visual distraction driving, while the superior frontal gyrus, right dorsolateral region were significantly activated during auditory distracted driving, and the right intraorbital superior frontal gyrus, right infraorbital frontal gyrus and superior frontal gyrus, and right dorsolateral region were significantly activated during cognitive distraction. This intrinsic neural activity in brain regions is expressed through extrinsic driving performance. It was found that auditory distracted driving, with the lowest activation in the right frontal lobe, had the least effect on lateral control of the vehicle, and cognitive distracted driving, with the highest activation in the right frontal lobe, had the greatest effect on lateral control of the vehicle. Therefore, we suggest that prefrontal cortical areas, especially the right frontal cortical area, are most affected by distracted driving.

Effects of face repetition on ventral visual stream connectivity using dynamic causal modelling of fMRI data

Stimulus repetition normally causes reduced neural activity in brain regions that process that stimulus. Some theories claim that this “repetition suppression” reflects local mechanisms such as neuronal fatigue or sharpening within a region, whereas other theories claim that it results from changed connectivity between regions, following changes in synchrony or top-down predictions. In this study, we applied dynamic causal modeling (DCM) on a public fMRI dataset involving repeated presentations of faces and scrambled faces to test whether repetition affected local (self-connections) and/or between-region connectivity in left and right early visual cortex (EVC), occipital face area (OFA) and fusiform face area (FFA). Face “perception” (faces versus scrambled faces) modulated nearly all connections, within and between regions, including direct connections from EVC to FFA, supporting a non-hierarchical view of face processing. Face “recognition” (familiar versus unfamiliar faces) modulated connections between EVC and OFA/FFA, particularly in the left hemisphere. Most importantly, immediate and delayed repetition of stimuli were also best captured by modulations of connections between EVC and OFA/FFA, but not self-connections of OFA/FFA, consistent with synchronization or predictive coding theories, though also possibly reflecting local mechanisms like synaptic depression.

Why he buys it and she doesn't – Exploring self-reported and neural gender differences in the perception of eCommerce websites

Studies of gender-related differences in the perception of ecommerce websites dependent on the websites' aesthetics, usefulness, ease of use, and purchase intentions, give contradictory results. To shed light on these conflicting findings, in addition to self-reported data from two online questionnaires (Study 1 & Study 2), our research uses the neuroimaging method of functional near-infrared spectroscopy to explore possible gender-related differences (Study 3). By conducting three studies, users’ conscious and unconscious (neural) evaluations of ecommerce websites are explored. The self-reported results reveal that men and women do not significantly differ in their expressed evaluations of ecommerce websites. However, the neural results indicate that gender-related differences in the perception of ecommerce websites are influenced by unconscious effects, which might explain the inconsistent gender-specific research findings. Men tend to require greater neural activity when using ecommerce websites. Websites evaluated as useful and visually aesthetic lead to significant neural activation in brain regions of the left hemisphere for men in comparison to women, whereas websites evaluated as less useful and appealing reveal neural activation in brain regions of the right hemisphere in male participants. The results provide several theoretical and practical implications for the evaluation of gender-specific decision making on ecommerce websites.

Political uncertainty moderates neural evaluation of incongruent policy positions

Uncertainty has been shown to impact political evaluation, yet the exact mechanisms by which uncertainty affects the minds of citizens remain unclear. This experiment examines the neural underpinnings of uncertainty in political evaluation using functional magnetic resonance imaging (fMRI). During fMRI, participants completed an experimental task where they evaluated policy positions attributed to hypothetical political candidates. Policy positions were either congruent or incongruent with candidates' political party affiliation and presented with varying levels of certainty. Neural activity was modelled as a function of uncertainty and incongruence. Analyses suggest that neural activity in brain regions previously implicated in affective and evaluative processing (anterior cingulate cortex, insular cortex) differed as a function of the interaction between uncertainty and incongruence, such that activation in these areas was greatest when information was both certain and incongruent, and uncertainty influenced processing differently as a function of the valence of the attached information. These findings suggest that individuals are attuned to uncertainty in the stated issue positions of politicians, and that the neural processing of this uncertainty is dependent on congruence of these positions with expectations based on political party identification. Implications for the study of emotion and politics and political cognition are discussed. This article is part of the theme issue 'The political brain: neurocognitive and computational mechanisms'.

Reforming Sectarian Beliefs in Iraq: Winning the Peace

Sectarian violence continues in Iraq affecting regional and world security. Neuroscience techniques are used to assess the mentalizing process and counter-arguing in response to videos designed to prevent extremist radicalization. Measurement of neural activity in brain Regions of Interest (ROI) assists identification of messages which can promote favorable behavior. Activation of the Medial Prefrontal Cortex (MPFC) is associated with message adoption and behavior change. Public Service Announcements (PSAs) have not been effective in reducing violence in Iraq. This study demonstrates that the four PSAs investigated in this study do not activate the MPFC. The RLPFC is a brain ROI associated with counter-arguing and message resistance. This study demonstrates that reduction in activity in the Right Lateral Prefrontal Cortex (RLPFC) is associated with decreased sectarianism. Engagement was measured and is associated with activity in the frontal pole regions.We introduce Functional Near-infrared Spectroscopy (fNIRS) to measure the neural activity of highly sectarian Iraqis in response to these anti-sectarian messages. Neural activity was measured while viewing three PSAs and a fourth unpublished video. All four videos are intended to reduce sectarianism. A novel sectarianism scale is introduced to measure sectarian beliefs before and after the messages. This sectarian scale has high internal consistency as measured by Cronbach’s alpha. Measured activation of brain ROIs are correlated with changes in the sectarian scale. Twelve Sunni and twelve Shi’a Iraqis participated in the study. Subjects were shown the four videos in randomized order, while equipped with a fNIRS neural imaging device. All four videos produced significant engagement. None of the videos reduced sectarianism nor caused brain activation of adoption. This is consistent with the widely held Iraqi public perception that the PSAs are ineffective. Only one video, which was un-published, caused reduced sectarian beliefs. This un-published fourth video was associated with decreased counter-arguing. Counter-arguing is associated with message resistance.

Measuring dlPFC Signals to Predict the Success of Merchandising Elements at the Point-of-Sale - A fNIRS Approach.

The (re-)launch of products is frequently accompanied by point-of-sale (PoS) marketing campaigns in order to foster sales. Predicting the success of these merchandising elements at the PoS on sales is of interest to research and practice, as the misinvestments that are based on the fragmented PoS literature are tremendous. Likewise, the predictive power of neuropsychological methods has been demonstrated in various research work. Nevertheless, the practical application of these neuropsychological methods is still limited. In order to foster the application of neuropsychological methods in research and practice, the current research work aims to explore, whether mobile functional near-infrared spectroscopy (fNIRS) – as a portable neuroimaging method – has the potential to predict the success of PoS merchandising elements by rendering significant neural signatures of brain regions of the dorsolateral prefrontal cortex (dlPFC), highlighting its potential to forecast shoppers’ behaviour aka sales at the PoS. Building on previous research findings, the results of the given research work indicate that the neural signal of brain regions of the dlPFC, measured with mobile fNIRS, is able to predict actual sales associated with PoS merchandising elements, relying on the cortical relief effect. More precisely, the research findings support the hypothesis that the reduced neural activity of brain regions associated with the dlPFC can predict sales at the PoS, emphasising another crucial neural signature to predict shoppers’ purchase behaviour, next to the frequently cited reward association system. The research findings offer an innovative perspective on how to design and evaluate PoS merchandising elements, indicating fruitful theoretical and practical implications.

Investigating holistic face processing within and outside of face-responsive brain regions

It has been shown that human faces are processed holistically (i.e. as indecomposable wholes, rather than by their component parts) and this holistic face processing is linked to brain activity in face-responsive brain regions. Although several brain regions outside of the face-responsive network are also sensitive to relational processing and perceptual grouping, whether these non-face-responsive regions contribute to holistic processing remains unclear. Here, we investigated holistic face processing in the composite face paradigm both within and outside of face-responsive brain regions. We recorded participants’ brain activity using fMRI while they performed a composite face task. Behavioural results indicate that participants tend to judge the same top face halves as different when they are aligned with different bottom face halves but not when they are misaligned, demonstrating a composite face effect. Neuroimaging results revealed significant differences in responses to aligned and misaligned faces in the lateral occipital complex (LOC), and trends in the anterior part of the fusiform face area (FFA2) and transverse occipital sulcus (TOS), suggesting that these regions are sensitive to holistic versus part-based face processing. Furthermore, the retrosplenial cortex (RSC) and the parahippocampal place area (PPA) showed a pattern of neural activity consistent with a holistic representation of face identity, which also correlated with the strength of the behavioural composite face effect. These results suggest that neural activity in brain regions both within and outside of the face-responsive network contributes to the composite-face effect.

Neural Correlates of Food Cue Exposure Intervention for Obesity: A Case-Series Approach.

BackgroundPeople with overweight have stronger reactivity (e.g., subjective craving) to food cues than lean people, and this reactivity is positively associated with food intake. Cue reactivity is a learned response that can be reduced with food cue exposure therapy.ObjectivesIt was hypothesized that participants after food cue exposure therapy would show reduced neural activity in brain regions related to food cue reactivity and increased neural activity in brain regions related to inhibitory-control as compared to participants receiving a control lifestyle intervention.MethodNeural activity of 10 women with overweight (BMI ≥ 27 kg/m2) in response to individually tailored visually presented palatable high-caloric food stimuli was examined before vs. after a cue exposure intervention (n = 5) or a control lifestyle (n = 5) intervention. Data were analyzed case-by-case.ResultsNeural responses to food stimuli were reduced in food-cue-reactivity-related brain regions after the lifestyle intervention in most participants, and generally not after the cue exposure therapy. Moreover, cue exposure did not lead to increased activity in inhibitory-control-related brain regions. However, decreased neural activity after cue exposure was found in most participants in the lateral occipital complex (LOC), which suggests a decreased visual salience of high-caloric food stimuli.ConclusionReceiving a cue exposure therapy did not lead to expected neural responses. As cue exposure relies on inhibitory learning mechanisms, differences in contexts (e.g., environments and food types) between the intervention setting and the scanning sessions may explain the general lack of effect of cue-exposure on neural activity.

ESTIMATING CAUSAL EFFECTS IN STUDIES OF HUMAN BRAIN FUNCTION: NEW MODELS, METHODS AND ESTIMANDS.

Neuroscientists often use functional magnetic resonance imaging (fMRI) to infer effects of treatments on neural activity in brain regions. In a typical fMRI experiment, each subject is observed at several hundred time points. At each point, the blood oxygenation level dependent (BOLD) response is measured at 100,000 or more locations (voxels). Typically, these responses are modeled treating each voxel separately, and no rationale for interpreting associations as effects is given. Building on Sobel and Lindquist (J. Amer. Statist. Assoc. 109 (2014) 967-976), who used potential outcomes to define unit and average effects at each voxel and time point, we define and estimate both "point" and "cumulated" effects for brain regions. Second, we construct a multisubject, multivoxel, multirun whole brain causal model with explicit parameters for regions. We justify estimation using BOLD responses averaged over voxels within regions, making feasible estimation for all regions simultaneously, thereby also facilitating inferences about association between effects in different regions. We apply the model to a study of pain, finding effects in standard pain regions. We also observe more cerebellar activity than observed in previous studies using prevailing methods.

Deliberation and Valence as Dissociable Components of Counterarguing among Smokers: Evidence from Neuroimaging and Quantitative Linguistic Analysis

ABSTRACT Counterarguing is a key obstacle to successful persuasion. However, the difficulty of directly measuring counterarguing during message exposure limits knowledge of the underlying mechanisms. The current study combines neuroimaging and linguistic measures to unpack neurocognitive and psychological mechanisms associated with counterarguing among a sample of established smokers in response to anti-smoking messaging. We capture participants’ neural activity in brain regions associated with effortful deliberation and negative argumentation during message exposure, and link it with their subsequent language patterns to further understanding of counterarguing in the brain. Greater brain activity within key regions of interest associated with deliberation and negative argumentation is associated with greater cognitive depth and less positivity in the post-scan message descriptions, respectively, among those who have lower intention to change their smoking behavior. We connect these neural representations of counterarguing with psychological theories and discuss implications that may increase the impact of persuasive communications.

A Functional Near-Infrared Spectroscopy Study on the Cortical Haemodynamic Responses During the Maastricht Acute Stress Test

In order to better understand stress responses, neuroimaging studies have investigated the underlying neural correlates of stress. Amongst other brain regions, they highlight the involvement of the prefrontal cortex. The aim of the present study was to explore haemodynamic changes in the prefrontal cortex during the Maastricht Acute Stress Test (MAST) using mobile functional Near-Infrared Spectroscopy (fNIRS), examining the stress response in an ecological environment. The MAST includes a challenging mental arithmic task and a physically stressful ice-water task. In a between-subject design, participants either performed the MAST or a non-stress control condition. FNIRS data were recorded throughout the test. Additionally, subjective stress ratings, heart rate and salivary cortisol were evaluated, confirming a successful stress induction. The fNIRS data indicated significantly increased neural activity of brain regions of the dorsolateral prefrontal cortex (dlPFC) and the orbitofrontal cortex (OFC) in response to the MAST, compared to the control condition. Furthermore, the mental arithmetic task indicated an increase in neural activity in brain regions of the dlPFC and OFC; whereas the physically stressful hand immersion task indicated a lateral decrease of neural activity in the left dlPFC. The study highlights the potential use of mobile fNIRS in clinical and applied (stress) research.

Abnormal spontaneous neural activity of brain regions in patients with primary blepharospasm at rest

BackgroundPrimary blepharospasm (BSP) is characterized by excessive involuntary eyelid spasms without significant morphological brain abnormalities. Its neural bases remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) is a powerful tool for exploring cerebral function mechanisms in BSP. MethodsTwo subject groups (24 patients with BSP and 24 healthy controls) underwent rs-fMRI scans. The rs-fMRI images were analyzed using the regional homogeneity (ReHo) method to assess the local features of spontaneous brain activity. Correlation analysis was carried out to explore the relationship between the ReHo values of abnormal brain areas and clinical variables including illness duration, symptom severity, and depression/anxiety symptoms. ResultsRelative to healthy controls, patients with BSP showed significantly decreased ReHo in the left superior temporal pole/left insula, left calcarine cortex, and bilateral superior medial frontal gyrus (mSFG), and increased ReHo in the bilateral supplementary motor area (SMA). There were no significant correlations between ReHo values in these brain regions and clinical variables in the patients. ConclusionsOur results suggest that abnormal spontaneous brain activity in multiple brain regions not limited to the basal ganglia may be trait alterations in the patients, which provides more insights into the pathogenesis of BSP.

SUN-474 Estradiol Protects Against High-Fat Diet-Induced Obesity and Anxiety in Female Mice

Menopause is characterized by a decline in ovarian function and a decrease in estrogens. This decrease in estrogens leads to changes in metabolic phenotype, increasing the risk of weight gain from fat, metabolic syndrome, and type 2 diabetes in postmenopausal women. Menopause is also associated with changes in anxiety and mood. Estradiol (E) exerts similar metabolic effects in female mice as in women. We and others have shown that ovariectomized mice fed a high-fat diet (HFD) become obese, while mice treated with E remain lean. Furthermore, in female mice, HFD increases anxiety, and E acts in specific brain regions to influence anxiety and energy metabolism. However, the mechanisms by which E and diet interact to affect anxiety in females are not well understood. The present study tested the hypothesis that E protects against HFD-induced anxiety-like behavior by altering neural activity in brain regions involved in energy regulation and anxiety. Eight-week-old C57BL6J mice were ovariectomized and implanted with capsules containing either E (50 μg E in 25 μl of 5% ETOH/sesame oil) or vehicle (V). Within each treatment group, mice were fed a standard diet (SD) for 10 days and then maintained on SD or switched to HFD for 26 more days. Mice were weighed and food intake was measured every three days. Starting on day 30, anxiety-like behavior was assessed with three behavior tests: 1) light-dark 2) open-field and 3) elevated plus maze, with an interval of 3 days between each test. To investigate the effects of HFD and E on anxiety-induced neural activity, animals were perfused after the last behavior test. Whole brains were cleared, labeled and imaged for Fos using immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO). The V mice on HFD weighed at least 32% more than all other groups on day 36, while E mice remained lean and had reduced food intake, indicating that E protects against HFD-induced obesity. HFD increased anxiety behavior in the elevated plus maze test as HFD-fed mice spent less time in the open arms (p=0.03). E reduced anxiety-like behavior in mice fed a HFD as measured by the light-dark test. E mice on HFD spent more time in the light compartment than V mice on HFD (p=0.02). E decreased anxiety-like behavior in the open-field test, as E mice entered the center zone more times than V mice (p=0.048). Interestingly, in mice fed a HFD, E decreased Fos expression in the paraventricular hypothalamic nucleus (q<0.1), bed nucleus of the stria terminalis (q<0.05), and the subparafascicular area of the thalamus (q<0.001), suggesting that E protects against HFD-induced anxiety by decreasing neural activity in these specific brain regions. These findings provide insight into the potential mechanisms by which estrogens and diet interact to regulate energy homeostasis and anxiety in postmenopausal women. Work was funded by Otsuka Pharmaceutical Development & Commercialization, Inc.

Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

What is inherited or acquired in neurodevelopmental conditions such as autism spectrum disorder (ASD) is not a fixed outcome, but instead is a vulnerability to a spectrum of traits, especially social difficulties. Identifying the biological mechanisms associated with vulnerability requires looking as early in life as possible, before the brain is shaped by postnatal mechanisms and/or the experiences of living with these traits. Animal studies suggest that susceptibility to neurodevelopmental disorders arises when genetic and/or environmental risks for these conditions alter patterns of synchronous brain activity in the perinatal period, but this has never been examined in human neonates. To assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns. In this cohort study of 36 neonates with and without a family history of ASD, neonates underwent magnetic resonance imaging at St Thomas Hospital in London, England, using a dedicated neonatal brain imaging system between June 23, 2015, and August 1, 2018. Neonates with a first-degree relative with ASD (R+) and therefore vulnerable to autistic traits and neonates without a family history (R-) were recruited for the study. Synchronous neural activity in brain regions linked to social function was compared. Regions responsible for social function were selected with reference to a published meta-analysis and the level of synchronous activity within each region was used as a measure of local functional connectivity in a regional homogeneity analysis. Group differences, controlling for sex, age at birth, age at scan, and group × age interactions, were examined. The final data set consisted of 18 R+ infants (13 male; median [range] postmenstrual age at scan, 42.93 [40.00-44.86] weeks) and 18 R- infants (13 male; median [range] postmenstrual age at scan, 42.50 [39.29-44.58] weeks). Neonates who were R+ had significantly higher levels of synchronous activity in the right posterior fusiform (t = 2.48; P = .04) and left parietal cortices (t = 3.96; P = .04). In addition, there was a significant group × age interaction within the anterior segment of the left insula (t = 3.03; P = .04) and cingulate cortices (right anterior: t = 3.00; P = .03; left anterior: t = 2.81; P = .03; right posterior: t = 2.77; P = .03; left posterior: t = 2.55; P = .03). In R+ infants, levels of synchronous activity decreased over 39 to 45 weeks' postmenstrual age, whereas synchronous activity levels increased in R- infants over the same period. Synchronous activity is required during maturation of functionally connected networks. This study found that in newborn humans, having a first-degree relative with ASD was associated with higher levels of local functional connectivity and dysmaturation of interconnected regions responsible for processing higher-order social information.