The impact of developmental stage, tissue type, and sex on DNA double-strand break repair in Drosophila melanogaster.

Accurate repair of DNA double-strand breaks (DSBs) is essential for the maintenance of genome integrity, as failure to repair DSBs can result in cell death. The cell has evolved two main mechanisms for DSB repair: non-homologous end-joining (NHEJ) and homology-directed repair (HDR), which includes single-strand annealing (SSA) and homologous recombination (HR). While certain factors like age and state of the chromatin are known to influence DSB repair pathway choice, the roles of developmental stage, tissue type, and sex have yet to be elucidated in multicellular organisms. To examine the influence of these factors, DSB repair in various embryonic developmental stages, larva, and adult tissues in Drosophila melanogaster was analyzed through molecular analysis of the DR-white assay using Tracking across Indels by DEcomposition (TIDE). The proportion of HR repair was highest in tissues that maintain the canonical (G1/S/G2/M) cell cycle and suppressed in both terminally differentiated and polyploid tissues. To determine the impact of sex on repair pathway choice, repair in different tissues in both males and females was analyzed. When molecularly examining tissues containing mostly somatic cells, males and females demonstrated similar proportions of HR and NHEJ. However, when DSB repair was analyzed in male and female premeiotic germline cells utilizing phenotypic analysis of the DR-white assay, there was a significant decrease in HR in females compared to males. This study describes the impact of development, tissue-specific cycling profile, and, in some cases, sex on DSB repair outcomes, underscoring the complexity of repair in multicellular organisms.

Spontaneous cortical dynamics from the first years to the golden years.

In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Healthy aging alters the oscillatory dynamics and fronto-parietal connectivity serving fluid intelligence.

Fluid intelligence (Gf) involves logical reasoning and novel problem-solving abilities. Often, abstract reasoning tasks like Raven's progressive matrices are used to assess Gf. Prior work has shown an age-related decline in fluid intelligence capabilities, and although many studies have sought to identify the underlying mechanisms, our understanding of the critical brain regions and dynamics remains largely incomplete. In this study, we utilized magnetoencephalography (MEG) to investigate 78 individuals, ages 20-65 years, as they completed an abstract reasoning task. MEG data was co-registered with structural MRI data, transformed into the time-frequency domain, and the resulting neural oscillations were imaged using a beamformer. We found worsening behavioral performance with age, including prolonged reaction times and reduced accuracy. MEG analyses indicated robust oscillations in the theta, alpha/beta, and gamma range during the task. Whole brain correlation analyses with age revealed relationships in the theta and alpha/beta frequency bands, such that theta oscillations became stronger with increasing age in a right prefrontal region and alpha/beta oscillations became stronger with increasing age in parietal and right motor cortices. Follow-up connectivity analyses revealed increasing parieto-frontal connectivity with increasing age in the alpha/beta frequency range. Importantly, our findings are consistent with the parieto-frontal integration theory of intelligence (P-FIT). These results further suggest that as people age, there may be alterations in neural responses that are spectrally specific, such that older people exhibit stronger alpha/beta oscillations across the parieto-frontal network during abstract reasoning tasks.

Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth.

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.

Somatosensory gating is related to behavioral and verbal outcomes in children with mild-to-severe hearing loss.

Sensory gating is a process by which the brain filters out redundant information to preserve neural resources for behaviorally relevant stimuli. Although studies have shown alterations in auditory and visual processing in children who are hard-of-hearing (CHH) relative to children with normal hearing (CNH), it is unclear whether these alterations extend to the somatosensory domain, and how aberrations in sensory processing affect sensory gating. In this study, CHH and CNH were presented with a paired-pulse median nerve stimulation during magnetoencephalography. Stimulus-related gamma neural activity was imaged and virtual time series from peak somatosensory responses were extracted. We found significant effects of both stimulus and group, as well as a significant group-by-stimulus interaction. CHH showed a larger response to stimulation overall, as well as greater differences in gamma power from the first to the second stimulus. However, when looking at the ratio rather than the absolute difference in power, CHH showed comparable gating to CNH. In addition, smaller gating ratios were correlated with better classroom behavior and verbal ability in CHH, but not CNH. Taken together, these data underscore the importance of considering how CHH experience their multisensory environment when interpreting outcomes and designing interventions.

Regular cannabis use alters the neural dynamics serving complex motor control.

Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high-density magnetoencephalography (MEG). The MEG data was transformed into the time-frequency domain and beta responses (16-24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole-brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group-by-time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher-order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge.

Riverine food environments and food security: a case study of the Mekong River, Cambodia.

Rivers are critical, but often overlooked, parts of food systems. They have multiple functions that support the food security, nutrition, health and livelihoods of the communities surrounding them. However, given current unsustainable food system practices, damming and climate change, the majority of the world's largest rivers are increasingly susceptible to environmental degradation, with negative implications for the communities that rely on them. Here we describe the dynamism and multifaceted nature of rivers as food environments (i.e. the place within food systems where people obtain their food) and their role in securing food security including improved diets and overall health. We also provide a conceptual framework that explain rivers as food environments within the broader food system and describe approaches to characterizing these food environments to better inform our understanding of how they influence food security and nutrition outcomes. Applying this framework to the Mekong River in Cambodia, we describe rivers as multifaceted wild food environments embedded within ecosystems, sociocultural and political environments and sectors of influence. We also explain the ways in which individual factors might influence how communities interact with this food environment. Developing and articulating food-related, ecosystem-specific frameworks and their constructs can guide implementation of policies aimed to improve specific public health or environmental sustainability outcomes. Our conceptual framework incorporates the multiple dimensions of rivers, which will aid future work and public health policy framing to better describe, understand and intervene to ensure protection of rivers' biodiversity and ecosystems as well as food security, health and livelihoods.

Souvent négligés, les cours d'eau jouent pourtant un rôle vital dans les systèmes alimentaires. Ils remplissent de nombreuses fonctions qui contribuent à la sécurité alimentaire, à la nutrition, à la santé et aux moyens de subsistance des communautés avoisinantes. Toutefois, en raison d'un système alimentaire actuel aux pratiques non durables, de la construction de barrages et du changement climatique, la plupart des grands fleuves et rivières du monde sont de plus en plus exposés aux dégradations environnementales, avec des conséquences néfastes pour les communautés qui en dépendent. Dans le présent document, nous évoquons le dynamisme et les multiples facettes des cours d'eau en tant qu'environnements alimentaires (c'est-à-dire l'endroit où les gens se procurent de la nourriture au sein d'un système alimentaire), ainsi que la manière dont ils favorisent la sécurité alimentaire, notamment par le biais d'un régime plus équilibré et d'une meilleure santé en général. Nous fournissons également un cadre conceptuel qui définit les cours d'eau comme environnements alimentaires au sein d'un système plus vaste et décrit les approches caractérisant ces environnements, afin que nous puissions mieux comprendre l'influence qu'ils exercent sur la sécurité alimentaire et la nutrition. En appliquant ce cadre au fleuve Mékong, au Cambodge, nous dévoilons les multiples facettes de ces environnements alimentaires naturels variés qui font partie intégrante des écosystèmes, des milieux politiques et socioculturels, mais aussi des sphères d'influence. Nous expliquons en outre la façon dont certains facteurs individuels sont susceptibles d'interférer dans les interactions que les communautés entretiennent avec cet environnement alimentaire. Développer et formuler des cadres et structures liés à l'alimentation, propres à chaque écosystème, peut orienter la mise en œuvre de mesures visant à améliorer des résultats spécifiques dans le domaine de la santé publique ou de la préservation de l'environnement. Notre cadre conceptuel inclut les différents aspects des cours d'eau, ce qui aidera à mener de futurs travaux et à élaborer des politiques de santé publique pour mieux les qualifier, les appréhender et intervenir en vue d'assurer la protection de la biodiversité et des écosystèmes fluviaux ainsi que la sécurité alimentaire, la santé et les moyens de subsistance.

Los ríos son partes fundamentales de los sistemas alimentarios, pero con frecuencia se ignoran. Tienen múltiples funciones que favorecen la seguridad alimentaria, la nutrición, la salud y los medios de vida de las comunidades que los rodean. Sin embargo, dadas las actuales prácticas insostenibles del sistema alimentario, la construcción de embalses y el cambio climático, la mayoría de los ríos más grandes del mundo son cada vez más susceptibles a la degradación medioambiental, con implicaciones negativas para las comunidades que dependen de ellos. En este documento, se describe el dinamismo y la naturaleza polifacética de los ríos como entornos alimentarios (es decir, el lugar dentro de los sistemas alimentarios donde las personas obtienen sus alimentos) y su función para garantizar la seguridad alimentaria, incluida la mejora de los hábitos alimentarios y la salud en general. Asimismo, se proporciona un marco conceptual que explica los ríos como entornos alimentarios dentro del sistema alimentario en su conjunto y se describen enfoques para caracterizar estos entornos alimentarios con el fin de comprender mejor cómo influyen en los resultados de la seguridad alimentaria y la nutrición. Mediante la aplicación de este marco al río Mekong en Camboya, se describen los ríos como entornos alimentarios silvestres multifacéticos integrados en ecosistemas, entornos socioculturales y políticos y sectores de influencia. Además, se explican cómo los factores individuales pueden influir en la interacción de las comunidades con este entorno alimentario. El desarrollo y la articulación de marcos específicos de los ecosistemas relacionados con la alimentación y sus constructos pueden orientar la aplicación de políticas destinadas a mejorar determinados resultados en materia de salud pública o sostenibilidad medioambiental. El marco conceptual que se presenta incorpora las múltiples dimensiones de los ríos, lo que ayudará en futuros trabajos y en la formulación de políticas de salud pública a describir, comprender e intervenir mejor para asegurar la protección de la biodiversidad y los ecosistemas fluviales, así como la seguridad alimentaria, la salud y los medios de subsistencia.

Elevated CRP and TNF-α levels are associated with blunted neural oscillations serving fluid intelligence.

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual's plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders.

Trauma moderates the development of the oscillatory dynamics serving working memory in a sex-specific manner.

Working memory, the ability to hold items in memory stores for further manipulation, is a higher order cognitive process that supports many aspects of daily life. Childhood trauma has been associated with altered cognitive development including particular deficits in verbal working memory (VWM), but the neural underpinnings remain poorly understood. Magnetoencephalography (MEG) studies of VWM have reliably shown decreased alpha activity in left-lateralized language regions during encoding, and increased alpha activity in parieto-occipital cortices during the maintenance phase. In this study, we examined whether childhood trauma affects behavioral performance and the oscillatory dynamics serving VWM using MEG in a cohort of 9- to 15-year-old youth. All participants completed a modified version of the UCLA Trauma History Profile and then performed a VWM task during MEG. Our findings indicated a sex-by-age-by-trauma three-way interaction, whereby younger females experiencing higher levels of trauma had the lowest d' accuracy scores and the strongest positive correlations with age (i.e. older performed better). Likewise, females with higher levels of childhood trauma exhibited altered age-related alpha changes during the maintenance phase within the right temporal and parietal cortices. These findings suggest that trauma exposure may alter the developmental trajectory of neural oscillations serving VWM processing in a sex-specific way.

Alpha oscillations in left perisylvian cortices support semantic processing and predict performance.

Semantic processing is the ability to discern and maintain conceptual relationships among words and objects. While the neural circuits serving semantic representation and controlled retrieval are well established, the neuronal dynamics underlying these processes are poorly understood. Herein, we examined 25 healthy young adults who completed a semantic relation word-matching task during magnetoencephalography (MEG). MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain statistical analyses were conducted to compare semantic-related to length-related neural oscillatory responses. Time series were extracted to visualize the dynamics and were linked to task performance using structural equation modeling. The results indicated that participants had significantly longer reaction times in semantic compared to length trials. Robust MEG responses in the theta (3-6 Hz), alpha (10-16 Hz), and gamma (64-76 Hz and 64-94 Hz) bands were observed in parieto-occipital and frontal cortices. Whole-brain analyses revealed stronger alpha oscillations in a left-lateralized network during semantically related relative to length trials. Importantly, stronger alpha oscillations in the left superior temporal gyrus during semantic trials predicted faster responses. These data reinforce existing literature and add novel temporal evidence supporting the executive role of the semantic control network in behavior.

In Addition to Stigma: Cognitive and Autism-Related Predictors of Mental Health in Transgender Adolescents.

OBJECTIVE: Autism spectrum disorder (ASD) is significantly over-represented among transgender adolescents. Independently, ASD and gender diversity are associated with increased mental health risks. Yet, mental health in autistic-transgender adolescents is poorly understood. This study investigates mental health in the largest matched sample to date of autistic-transgender, non-autistic (allistic) transgender, and autistic-cisgender adolescents diagnosed using gold-standard ASD diagnostic procedures. In accordance with advancing understanding of sex/gender-related autism phenotypes, slightly subthreshold autistic diagnostic presentations (common in autistic girls/women) are modeled. METHOD: This study includes 93 adolescents aged 13-21, evenly divided between autistic-transgender, autistic-cisgender, and allistic-transgender groups; 13 transgender adolescents were at the margin of ASD diagnosis and included within a larger "broad-ASD" grouping. Psychological and neuropsychological evaluation included assessment of mental health, IQ, LGBT stigma, ASD-related social symptoms, executive functioning (EF), and EF-related barriers to achieving gender-related needs. RESULTS: Autistic-transgender adolescents experienced significantly greater internalizing symptoms compared to allistic-transgender and autistic-cisgender groups. In addition to stigma-related associations with mental health, ASD-related cognitive/neurodevelopmental factors (i.e., poorer EF and greater social symptoms) were associated with worse mental health: specifically, social symptoms and EF gender barriers with greater internalizing and EF problems and EF gender barriers with greater suicidality. Comparing across all ASD and gender-related groups, female gender identity was associated with greater suicidality. CONCLUSIONS: Parsing the heterogeneity of mental health risks among transgender youth is critical for developing targeted assessments and interventions. This study identifies ASD diagnosis, ASD phenotypic characteristics, and EF-related gender barriers as potential risks for poorer mental health in transgender adolescents.

Longitudinal changes in the neural oscillatory dynamics underlying abstract reasoning in children and adolescents.

Fluid reasoning is the ability to problem solve in the absence of prior knowledge and is commonly conceptualized as "non-verbal" intelligence. Importantly, fluid reasoning abilities rapidly develop throughout childhood and adolescence. Although numerous studies have characterized the neural underpinnings of fluid reasoning in adults, there is a paucity of research detailing the developmental trajectory of this neural processing. Herein, we examine longitudinal changes in the neural oscillatory dynamics underlying fluid intelligence in a sample of typically developing youths. A total of 34 participants age 10 to 16 years-old completed an abstract reasoning task during magnetoencephalography (MEG) on two occasions set one year apart. We found robust longitudinal optimization in theta, beta, and gamma oscillatory activity across years of the study across a distributed network commonly implicated in fluid reasoning abilities. More specifically, activity tended to decrease longitudinally in additional, compensatory areas such as the right lateral prefrontal cortex and increase in areas commonly utilized in mature adult samples (e.g., left frontal and parietal cortices). Importantly, shifts in neural activity were associated with improvements in task performance from one year to the next. Overall, the data suggest a longitudinal shift in performance that is accompanied by a reconfiguration of the functional oscillatory dynamics serving fluid reasoning during this important period of development.

The development of sensorimotor cortical oscillations is mediated by pubertal testosterone.

Puberty is a period of substantial hormonal fluctuations, and pubertal hormones can modulate structural and functional changes in the developing brain. Many previous studies have characterized the neural oscillatory responses serving movement, which include a beta event-related desynchronization (ERD) preceding movement onset, gamma and theta responses coinciding with movement execution, and a post-movement beta-rebound (PMBR) response following movement offset. While a few studies have investigated the developmental trajectories of these neural oscillations serving motor control, the impact of pubertal hormone levels on the maturation of these dynamics has not yet been examined. Since the timing and tempo of puberty varies greatly between individuals, pubertal hormones may uniquely impact the maturation of motor cortical oscillations distinct from other developmental metrics, such as age. In the current study we quantified these oscillations using magnetoencephalography (MEG) and utilized chronological age and measures of endogenous testosterone as indices of development during the transition from childhood to adolescence in 69 youths. Mediation analyses revealed complex maturation patterns for the beta ERD, in which testosterone predicted both spontaneous baseline and ERD power through direct and indirect effects. Age, but not pubertal hormones, predicted motor-related theta, and no relationships between oscillatory responses and developmental metrics were found for gamma or PMBR responses. These findings provide novel insight into how pubertal hormones affect motor-related oscillations, and highlight the continued development of motor cortical dynamics throughout the pubertal period.

Differential impact of movement on the alpha and gamma dynamics serving visual processing.

Visual processing is widely understood to be served by a decrease in alpha activity in occipital cortices, largely concurrent with an increase in gamma activity. Although the characteristics of these oscillations are well documented in response to a range of complex visual stimuli, little is known about how these dynamics are impacted by concurrent motor responses, which is problematic as many common visual tasks involve such responses. Thus, in the current study, we used magnetoencephalography (MEG) and modified a well-established visual paradigm to explore the impact of motor responses on visual oscillatory activity. Thirty-four healthy adults viewed a moving gabor (grating) stimulus that was known to elicit robust alpha and gamma oscillations in occipital cortices. Frequency and power characteristics were assessed statistically for differences as a function of movement condition. Our results indicated that occipital alpha significantly increased in power during movement relative to no movement trials. No differences in peak frequency or power were found for gamma responses between the two movement conditions. These results provide valuable evidence of visuomotor integration and underscore the importance of careful task design and interpretation, especially in the context of complex visual processing, and suggest that even basic motor responses alter occipital visual oscillations in healthy adults.NEW & NOTEWORTHY Processing of visual stimuli is served by occipital alpha and gamma activity. Many studies have investigated the impact of visual stimuli on motor cortical responses, but few studies have systematically investigated the impact of motor responses on visual oscillations. We found that when participants are asked to move in response to a visual stimulus, occipital alpha power was modulated whereas gamma responses were unaffected. This suggests that these responses have dissociable roles in visuomotor integration.

Amount of Hearing Aid Use Impacts Neural Oscillatory Dynamics Underlying Verbal Working Memory Processing for Children With Hearing Loss.

OBJECTIVES: Children with hearing loss (CHL) may exhibit spoken language delays and may also experience deficits in other cognitive domains including working memory. Consistent hearing aid use (i.e., more than 10 hours per day) ameliorates these language delays; however, the impact of hearing aid intervention on the neural dynamics serving working memory remains unknown. The objective of this study was to examine the association between the amount of hearing aid use and neural oscillatory activity during verbal working memory processing in children with mild-to-severe hearing loss. DESIGN: Twenty-three CHL between 8 and 15 years-old performed a letter-based Sternberg working memory task during magnetoencephalography (MEG). Guardians also completed a questionnaire describing the participants' daily hearing aid use. Each participant's MEG data was coregistered to their structural MRI, epoched, and transformed into the time-frequency domain using complex demodulation. Significant oscillatory responses corresponding to working memory encoding and maintenance were independently imaged using beamforming. Finally, these whole-brain source images were correlated with the total number of hours of weekly hearing aid use, controlling for degree of hearing loss. RESULTS: During the encoding period, hearing aid use negatively correlated with alpha-beta oscillatory activity in the bilateral occipital cortices and right precentral gyrus. In the occipital cortices, this relationship suggested that with greater hearing aid use, there was a larger suppression of occipital activity (i.e., more negative relative to baseline). In the precentral gyrus, greater hearing aid use was related to less synchronous activity (i.e., less positive relative to baseline). During the maintenance period, hearing aid use significantly correlated with alpha activity in the right prefrontal cortex, such that with greater hearing aid use, there was less right prefrontal maintenance-related activity (i.e., less positive relative to baseline). CONCLUSIONS: This study is the first to investigate the impact of hearing aid use on the neural dynamics that underlie working memory function. These data show robust relationships between the amount of hearing aid use and phase-specific neural patterns during working memory encoding and maintenance after controlling for degree of hearing loss. Furthermore, our data demonstrate that wearing hearing aids for more than ~8.5 hours/day may serve to normalize these neural patterns. This study also demonstrates the potential for neuroimaging to help determine the locus of variability in outcomes in CHL.

Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms, Autism Spectrum Disorder, and Gender-Affirming Medical Treatment Status.

Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11-21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths' experiences, EF skill monitoring-and when appropriate, supports-should be considered for transgender youth.

High-definition transcranial direct current stimulation modulates performance and alpha/beta parieto-frontal connectivity serving fluid intelligence.

Fluid intelligence (Gƒ) includes logical reasoning abilities and is an essential component of normative cognition. Despite the broad consensus that parieto-prefrontal connectivity is critical for Gƒ (e.g. the parieto-frontal integration theory of intelligence, P-FIT), the dynamics of such functional connectivity during logical reasoning remains poorly understood. Further, given the known importance of these brain regions for Gƒ, numerous studies have targeted one or both of these areas with non-invasive stimulation with the goal of improving Gƒ, but to date there remains little consensus on the overall stimulation-related effects. To examine this, we applied high-definition direct current anodal stimulation to the left and right dorsolateral prefrontal cortex (DLPFC) of 24 healthy adults for 20 min in three separate sessions (sham, left, and right active). Following stimulation, participants completed a logical reasoning task during magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer, and peak task-induced activity was subjected to dynamic functional connectivity analyses to evaluate the impact of distinct stimulation montages on network activity. We found that participants responded faster following right DLPFC stimulation vs. sham. Moreover, our neural findings followed a similar trajectory of effects such that left parieto-frontal connectivity decreased following right and left DLPFC stimulation compared to sham, with connectivity following right stimulation being significantly correlated with the faster reaction times. Importantly, our findings are consistent with P-FIT, as well as the neural efficiency hypothesis (NEH) of intelligence. In sum, this study provides evidence for beneficial effects of right DLPFC stimulation on logical reasoning. KEY POINTS: Logical reasoning is an indispensable component of fluid intelligence and involves multispectral oscillatory activity in parietal and frontal regions. Parieto-frontal integration is well characterized in logical reasoning; however, its direct neural quantification and neuromodulation by brain stimulation remain poorly understood. High-definition transcranial direct current stimulation of dorsolateral prefrontal cortex (DLPFC) had modulatory effects on task performance and neural interactions serving logical reasoning, with right stimulation showing beneficial effects. Right DLPFC stimulation led to a decrease in the response time (i.e. better task performance) and left parieto-frontal connectivity with a marginal positive association between behavioural and neural metrics. Other modes of targeted stimulation of DLPFC (e.g. frequency-specific) can be employed in future studies.

Response certainty during bimanual movements reduces gamma oscillations in primary motor cortex.

Even when movement outputs are identical, the neural responses supporting them might differ substantially in order to adapt to changing environmental contexts. Despite the essential nature of this adaptive capacity of the human motor system, little is known regarding the effects of contextual response (un)certainty on the neural dynamics known to serve motor processing. In this study, we use a novel bimanual motor task and neuroimaging with magnetoencephalography (MEG) to examine the effects of contextual response certainty on the dynamic neural responses that are important for proper movement. Significant neural responses were identified in the time-frequency domain at the sensor-level and imaged to the cortex using a spectrally resolved beamformer. Combined frequentist and Bayesian statistical testing between neural motor responses under certain and uncertain conditions indicated evidence for no conditional effect on the peri-movement beta desynchronization (18 - 28 Hz; -100 to 300 ms). In contrast, the movement-related gamma synchronization (MRGS; 66 - 86 Hz; -50 to 150 ms) exhibited a robust effect of motor certainty, such that increased contextual response certainty reduced the amplitude of this response. Interestingly, the peak frequency of the MRGS was unaffected by response certainty. These findings both advance our understanding of the neural processes required to adapt our movements under altered environmental contexts, and support the growing conceptualization of the MRGS as being reflective of ongoing higher cognitive processes during movement execution.

'Black and white and every wrong colour': The medical history of Jane Austen and the possibility of systemic lupus erythematosus.

Jane Austen died 200 years ago at the age of 41 and authors have attributed her premature death to a wide variety of causes, which include Addison's disease and lymphoma.We have reviewed all of her available letters and extricated relevant medical information which reveal rheumatism, facial skin lesions, fever and marked fluctuation of these symptoms. The severity of these symptoms increased, leading to her death within a year.This range of clinical features fulfils the most recent classification criteria for systemic lupus erythematosus.

Parietal Oscillatory Dynamics Mediate Developmental Improvement in Motor Performance.

Numerous recent studies have sought to determine the developmental trajectories of motor-related oscillatory responses from youth to adulthood. However, most of this work has relied on simple movements, and rarely have these studies linked developmental neural changes with maturational improvements in motor performance. In this study, we recorded magnetoencephalography during a complex finger-tapping task in a large sample of 107 healthy youth aged 9-15 years old. The relationships between region-specific neural activity, age, and performance metrics were examined using structural equation modeling. We found strong developmental effects on behavior and beta oscillatory activity during movement planning, as well as associations between planning-related beta activity and activity within the same region during the movement execution period. However, when all factors were tested, we found that only right parietal cortex beta dynamics mediated the relationship between age and performance on the task. These data suggest that strong, sustained beta activity within the right parietal cortex enhances motor performance, and that these sustained oscillations develop through childhood into early adolescence. In sum, these are the first data to link developmental trajectories in beta oscillatory dynamics with distinct motor performance metrics and implicate the right parietal cortex as a crucial hub in movement execution.