Critical Developmental Period Research Articles

The Impact of Non-Physical Bullying on Adolescents' Self-Concept: An Observational Study in the Adolescent Community in Sausapor, Tambrauw Regency, West Papua, Indonesia

Introduction: Non-physical bullying, often subtle and insidious, poses a significant threat to adolescents' self-concept during a critical developmental period. This study investigates the prevalence and impact of non-physical bullying on adolescents' self-concept within the unique cultural context of Sausapor, Tambrauw Regency, West Papua, Indonesia. Methods: A cross-sectional observational study was conducted among adolescents aged 12-17 years in Sausapor. Data were collected using validated questionnaires assessing non-physical bullying experiences and self-concept dimensions (self-esteem, self-efficacy, and body image). Descriptive statistics, chi-square tests, and regression analyses were employed to examine the relationship between non-physical bullying and self-concept. Results: The study revealed a significant prevalence of non-physical bullying in the Sausapor adolescent community, with verbal abuse and social exclusion being the most common forms. Non-physical bullying was significantly associated with lower self-esteem, reduced self-efficacy, and negative body image among adolescents. Regression analyses confirmed the detrimental impact of non-physical bullying on self-concept, even after controlling for sociodemographic factors. Conclusion: Non-physical bullying is a pervasive issue in Sausapor, with profound negative consequences for adolescents’ self-concept. Culturally sensitive interventions are urgently needed to prevent and address non-physical bullying, promote positive self-concept development, and foster a supportive environment for adolescents in this community.

Children's Memory for Events: The Challenge of Free Recall.

Early childhood is a critical period for episodic memory development, with sharp behavioral improvements between ages 4 to 7 years. Prior work has demonstrated this extensively with prompted memory tasks, but we explored performance on unprompted, free recall of a naturalistic experience in children, and how their performance relates to other cognitive measures. We asked children and adults to view a television episode, a naturalistic task for which there exists a ground truth, and assessed their free recall memory for the episode. Children's free recall performance improved dramatically with age, with many young children producing no verbal free recall whatsoever, although prompted recognition memory measures showed retention of material. However, the detail in free recall was related to both recognition and temporal order forced-choice memory performance in our full sample, showing agreement among memory measures. Free recall was strongly predicted by verbal skills, suggesting that children's sparse recall reflects verbal skill development rather than a pure mnemonic deficit. We propose that free recall has a more protracted developmental trajectory because it requires more substantial verbal skills as well as metacognitive skills that direct memory search, as compared with forced-choice memory tasks.

Empathy Capacity-Building through a Community of Practice Approach: Exploring Perceived Impacts and Implications

Empathy can be a powerful catalyst for caring action toward wildlife and nature more broadly. Given the critical developmental period of early childhood, interventions that build the capacity of educators to support empathy development in young children are needed. We report on an evaluation of an empathy-focused Community of Practice (CoP) that engaged 15 regional early childhood professionals (including four zoo preschool staff) in the co-creation of empathy practices that are deepened through a ‘Two-Worlds’ (Indigenous and Western) approach. Ripple effect mapping was the evaluation approach used, as its participatory nature and emphasis on reflection were well aligned with the CoP approach. The results suggest CoP participation influenced teachers’ capacity for supporting empathy development, which rippled outward from teacher-level impacts to positive impacts on children, families, and beyond. We also offer reflections on the use of a CoP approach to build individual, organizational, and community capacity for supporting empathy, as well as on the conduciveness of ripple effect mapping for evaluating capacity-building professional learning in the context of empathy conservation.

Acute social defeat during adolescence promotes long-lasting aggression through activation of the medial amygdala

Traumatic stress, particularly during critical developmental periods such as adolescence, has been strongly linked to an increased propensity and severity of aggression. Existing literature underscores that being a victim of abuse can exacerbate aggressive behaviors, with the amygdala playing a pivotal role in mediating these effects. Historically, animal models have demonstrated that traumatic stressors can increase attack behavior, implicating various amygdala nuclei. Building on this foundation, our previous work has highlighted how traumatic stress invokes long-lasting aggression via an excitatory pathway within the posterior ventral medial amygdala (MeApv). In the current study, we sought to further delineate this mechanism by examining the effects of acute social defeat during adolescence on aggressive behaviors and neural activation in mice. Using a common social defeat paradigm, we first established that acute social defeat during late adolescence indeed promotes long-lasting aggression, measured as attack behavior 7 days after the defeat session. Immunolabeling with c-Fos demonstrated that acute social defeat activates the MeApv and ventrolateral aspect of the ventromedial hypothalamus (VmHvl), consistent with our previous studies that used foot shock as an acute stressor. Finally, chemogenetically inhibiting excitatory MeApv neurons during social defeat significantly mitigated the aggression increase without affecting non-aggressive social behavior. These results strongly suggest that the MeApv plays a critical role in the onset of aggression following traumatic social experience, and offer the MeA as a potential target for therapeutic interventions.

Unravelling the Cerebellar Involvement in Autism Spectrum Disorders: Insights into Genetic Mechanisms and Developmental Pathways

Autism spectrum disorders (ASDs) are complex neurodevelopmental conditions characterized by deficits in social interaction and communication, as well as repetitive behaviors. Although the etiology of ASD is multifactorial, with both genetic and environmental factors contributing to its development, a strong genetic basis is widely recognized. Recent research has identified numerous genetic mutations and genomic rearrangements associated with ASD-characterizing genes involved in brain development. Alterations in developmental programs are particularly harmful during critical periods of brain development. Notably, studies have indicated that genetic disruptions occurring during the second trimester of pregnancy affect cortical development, while disturbances in the perinatal and early postnatal period affect cerebellar development. The developmental defects must be viewed in the context of the role of the cerebellum in cognitive processes, which is now well established. The present review emphasizes the genetic complexity and neuropathological mechanisms underlying ASD and aims to provide insights into the cerebellar involvement in the disorder, focusing on recent advances in the molecular landscape governing its development in humans. Furthermore, we highlight when and in which cerebellar neurons the ASD-associated genes may play a role in the development of cortico–cerebellar circuits. Finally, we discuss improvements in protocols for generating cerebellar organoids to recapitulate the long period of development and maturation of this organ. These models, if generated from patient-induced pluripotent stem cells (iPSC), could provide a valuable approach to elucidate the contribution of defective genes to ASD pathology and inform diagnostic and therapeutic strategies.

Temperature-Dependent Sex Determination in Crocodilians and Climate Challenges

The sex of crocodilians is determined by the temperature to which the eggs, and hence the developing embryo are exposed during critical periods of development. Temperature-dependent sex determination is a process that occurs in all crocodilians and numerous other reptile taxa. The study of artificial incubation temperatures in different species of crocodiles and alligators has determined the specific temperature ranges that result in altered sex ratios. It has also revealed the precise temperature thresholds at which an equal number of males and females are generated, as well as the specific developmental period during which the sex of the hatchlings may be shifted. This review will examine the molecular basis of the sex-determination mechanism in crocodilians elucidated during recent decades. It will focus on the many patterns and theories associated with this process. Additionally, we will examine the consequences that arise after hatching due to changes in incubation temperatures, as well as the potential benefits and dangers of a changing climate for crocodilians who display sex determination based on temperature.

Temperature-Dependent Sex Determination in Crocodilians and Climate Challenges.

The sex of crocodilians is determined by the temperature to which the eggs, and hence the developing embryo are exposed during critical periods of development. Temperature-dependent sex determination is a process that occurs in all crocodilians and numerous other reptile taxa. The study of artificial incubation temperatures in different species of crocodiles and alligators has determined the specific temperature ranges that result in altered sex ratios. It has also revealed the precise temperature thresholds at which an equal number of males and females are generated, as well as the specific developmental period during which the sex of the hatchlings may be shifted. This review will examine the molecular basis of the sex-determination mechanism in crocodilians elucidated during recent decades. It will focus on the many patterns and theories associated with this process. Additionally, we will examine the consequences that arise after hatching due to changes in incubation temperatures, as well as the potential benefits and dangers of a changing climate for crocodilians who display sex determination based on temperature.

Discrimination experiences and problematic alcohol and cannabis use in young adulthood.

Limited research has examined how discrimination in young adulthood relates to substance use. We examined how multiple and specific types (e.g., race-based) of experiences of unfair treatment are related to problematic alcohol and cannabis use. We analyzed cross-sectional data from a diverse cohort of young adults (mean age 24.7) predominantly residing in southern California (n = 2303) to examine associations of multiple (count) and specific experiences (race-, sexual orientation-, gender-based) of perceived everyday discrimination with self-reported alcohol and cannabis use outcomes (consequences, use disorders, and solitary use). We also tested interactions between the three specific discrimination experiences and sociodemographic characteristics (e.g., race-based discrimination × race/ethnicity). In this diverse sample (e.g., 47% Latinx/o and 22% Asian; 22% sexual/gender diverse; 56% female) of young adults, about 46% reported up to four different discrimination experiences and 27% reported race-, 26% gender-, and 5% sexual orientation-based discrimination. Race- and gender-based discrimination and experiencing more types of discrimination were associated with worse cannabis use outcomes. Race-based discrimination was associated with fewer alcohol consequences and lower Alcohol Use Disorders Identification Test (AUDIT) scores. Associations with sexual orientation-based discrimination and the interactions were not significant. Findings build on limited research on associations of discrimination with cannabis use in young adults. More work is needed to understand the mechanisms by which discrimination influences drinking behaviors. This study advances the field by examining the unique contributions of specific and multiple types of discrimination experiences in young adulthood, a critical developmental period in which substance use peaks.

Research progress on the association between screen content and mental health issue in children and adolescents

With the wide use of screen media, screen exposure shows a trend of younger age, and the screen exposure of children and adolescents has become a global public health issue of concern. Childhood and adolescence are important stages of growth and development, as well as critical periods of cognitive ability, emotional development and socialization. Previous studies have shown that screen time is closely related to the mental health of children and adolescents, but few studies have focused on the correlation between screen content and their mental health. The screen content for children and adolescents mainly comes from traditional TV and emerging interactive electronic media. Children and adolescents are highly sensitive to screen content. This paper summarizes the current situation of screen content for children and adolescents and reviews the correlation between screen content and their mental health issues. It also reveals the potential mechanism of the correlation between the two to provide a theoretical basis for the selection and supervision of screen content for children and adolescents.

Adaptation and Validation of the Post-Pandemic Health Promotion Behavior of Young Adults in the Digital Age (PS-SGD) Scale in the Turkish Population.

Young adulthood is a critical developmental period in which individuals establish life-long health behaviors and take responsibility for their own health care. Health promotion strategies tailored to young adults, leveraging digital tools, and addressing challenges exacerbated by events like the COVID-19 pandemic are needed. The aim of this study was to adapt the post-pandemic health promotion behavior of young adults in the digital age (PS-SGD) scale to the Turkish population in order to assess and compare the health behavior of young adults after the pandemic. A total of 312 participants, aged between 19 and 29 years, were included in the study via non-probabilistic criterion sampling, while the Turkish adaptation process started with translation and back translation methods performed with three language and two health science experts. For statistical analysis, EFA and CFA were conducted to evaluate internal consistency and structural validity. Confirmatory factor analysis was utilized to confirm the structure of the six sub-dimensions. Additionally, measurement invariance was examined regarding participants' gender to determine if the scale accurately captured similar traits across diverse groups. The relationship between the test-retest data was tested by Pearson correlation to measure consistency and its invariance over time. The gender distribution of the sample was found to be 61.3% female and 38.7% male. According to the results of EFA, items 8 and 18 were removed from the Turkish-adapted version. As a result of the reliability analysis conducted with the Turkish version of the scale, the Cronbach alpha coefficient was obtained as 0.851 for the post-pandemic health promotion behavior. Additionally, the scale was rated as reliable with the following Cronbach alpha values: 0.79 for the "personal hygiene", 0.78 for "dietary habits", 0.72 for "using mobile devices", 0.70 for "emotional health", 0.68 for "health care and physical activity", and 0.51 for "social health" sub-dimensions. To examine the six sub-dimension factor structures of the scale, fit indices were calculated as χ2/df (1.722), GFI (0.894), IFI (0.908), TLI (0.892), CFI (0.907), RMSEA (0.048), and SRMR (0.057) and were within acceptable limits. Findings of the multi-group confirmatory factor analysis for measurement invariance were less than or equal to 0.01 for the ∆CFI and ∆RMSEA values across all indices. Consequently, it was observed that the item-factor structure, factor loadings, variances, covariances, and error variances of the scale were equivalent for both male and female young adults, while test-retest results showed a high positive correlation. The Turkish version of the post-pandemic health promotion behavior scale of young adults in the digital age scale, consisting of 25 items and six subscales, was proven to be a valid and reliable tool to measure health promotion behavior in young adults aged 19-29 years.

Glia control experience-dependent plasticity in an olfactory critical period.

Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The Drosophila antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience. We recently found that glia regulate the development of the antennal lobe in young adult flies, leading us to ask if glia also drive experience-dependent plasticity. Here we define a critical period for structural and functional plasticity of OSN-PN synapses in the ethyl butyrate (EB)-sensitive glomerulus VM7. EB exposure for the first two days post-eclosion drives large-scale reductions in glomerular volume, presynapse number, and post-synaptic activity. The highly conserved engulfment receptor Draper is required for this critical period plasticity. Specifically, ensheathing glia upregulate Draper expression, invade the VM7 glomerulus, and phagocytose OSN presynaptic terminals in response to critical-period EB exposure. Crucially, synapse pruning during the critical period has long-term consequences for circuit function since both OSN-PN synapse number and spontaneous activity of PNs remain persistently decreased. These data demonstrate experience-dependent pruning of synapses in olfactory circuitry and argue that the Drosophila antennal lobe will be a powerful model for defining the function of glia in critical period plasticity.

Floral Response to Heat: A Study of Color and Biochemical Adaptations in Purple Chrysanthemums.

Chrysanthemums are among the world's most popular cut flowers, with their color being a key ornamental feature. The formation of these colors can be influenced by high temperatures. However, the regulatory mechanisms that control the fading of chrysanthemum flower color under high-temperature stress remain unclear. This study investigates the impact of high temperatures on the color and biochemical responses of purple chrysanthemums. Four purple chrysanthemum varieties were exposed to both normal and elevated temperature conditions. High-temperature stress elicited distinct responses among the purple chrysanthemum varieties. 'Zi Feng Che' and 'Chrystal Regal' maintained color stability, whereas 'Zi Hong Tuo Gui' and 'Zi lian' exhibited significant color fading, particularly during early bloom stages. This fading was associated with decreased enzymatic activities, specifically of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), indicating a critical period of color development under heat stress. Additionally, the color fading of 'Zi Lian' was closely related to the increased activity of the peroxidase (POD) and polyphenol oxidase (PPO). Conversely, a reduction in β-glucosidase (βG) activity may contribute significantly to the color steadfastness of 'Zi Feng Che'. The genes Cse_sc027584.1_g010.1 (PPO) and Cse_sc031727.1_g010.1 (POD) might contribute to the degradation of anthocyanins in the petals of 'Zi Hong Tuo Gui' and 'Zi Lian' under high-temperature conditions, while simultaneously maintaining the stability of anthocyanins in 'Zi Feng Che' and 'Chrystal Regal' at the early bloom floral stage. The findings of this research provide new insights into the physiological and biochemical mechanisms by which chrysanthemum flower color responds to high-temperature stress.

Chronic Adolescent Restraint Stress Downregulates miRNA-200a Expression in Male and Female C57BL/6J and BALB/cJ Mice

Adolescence is a critical developmental period when the brain is plastic, and stress exposure can have lasting physiological consequences. One mechanism through which adolescent stress may have lasting effects is by altering microRNAs (miRNAs), leading to wide-scale gene expression changes. Three prior independent studies used unbiased approaches (RNA sequencing or microarray) to identify miRNAs differentially expressed by chronic variable stress in male rodents. In all three studies, miRNA-200a was differentially expressed in areas of the brain associated with emotion regulation. The current study extends this research to determine if chronic non-variable adolescent stress downregulates miRNA-200a expression by looking at two strains (BALB/cJ and C57BL/6J) of male and female mice. We utilized a 14-day (2 h/day) restraint stress protocol and verified stress effects on adolescent body weight gain and circulating corticosterone concentrations relative to non-restraint controls. Mice were then left undisturbed until they were euthanized in adulthood, at which time brains were collected to measure miRNA-200a in the ventral hippocampus. Three weeks after adolescent stress ended, differences in body weight between groups were no longer significant; however, animals exposed to stress had less miRNA-200a expression in the ventral hippocampus than control animals. These data implicate miRNA-200a expression as a potential mechanism by which adolescent stress can have persistent impacts on multiple outcomes in both male and female mice.

Tutor auditory memory for guiding sensorimotor learning in birdsong.

Memory-guided motor shaping is necessary for sensorimotor learning. Vocal learning, such as speech development in human babies and song learning in bird juveniles, begins with the formation of an auditory template by hearing adult voices followed by vocally matching to the memorized template using auditory feedback. In zebra finches, the widely used songbird model system, only males develop individually unique stereotyped songs. The production of normal songs relies on auditory experience of tutor's songs (commonly their father's songs) during a critical period in development that consists of orchestrated auditory and sensorimotor phases. "Auditory templates" of tutor songs are thought to form in the brain to guide later vocal learning, while formation of "motor templates" of own song has been suggested to be necessary for the maintenance of stereotyped adult songs. Where these templates are formed in the brain and how they interact with other brain areas to guide song learning, presumably with template-matching error correction, remains to be clarified. Here, we review and discuss studies on auditory and motor templates in the avian brain. We suggest that distinct auditory and motor template systems exist that switch their functions during development.

Dopamine receptors and key elements of the neurotrophins (BDNF, CDNF) expression patterns during critical periods of ontogenesis in the brain structures of mice with autism-like behavior (BTBR) or its absence (С57BL/6 J).

Analysis of the mechanisms underlying autism spectrum disorder (ASD) is an urgent task due to the ever-increasing prevalence of this condition. The study of critical periods of neuroontogenesis is of interest, since the manifestation of ASD is often associated with prenatal disorders of the brain development. One of the currently promising hypotheses postulates a connection between the pathogenesis of ASD and the dysfunction of neurotransmitters and neurotrophins. In this study, we investigated the expression of key dopamine receptors (Drd1, Drd2), brain-derived neurotrophic factor (Bdnf), its receptors (Ntrkb2, Ngfr) and the transcription factor Creb1 that mediates BDNF action, as well as cerebral dopamine neurotrophic factor (Cdnf) during the critical periods of embryogenesis (e14 and e18) and postnatal development (p14, p28, p60) in the hippocampus and frontal cortex of BTBR mice with autism-like behavior compared to the neurotypical C57BL/6 J strain. In BTBR embryos, on the 14th day of prenatal development, an increase in the expression of the Ngfr gene encoding the p75NTR receptor, which may lead to the activation of apoptosis, was found in the hippocampus and frontal cortex. A decrease in the expression of Cdnf, Bdnf and its receptor Ntrkb2, as well as dopamine receptors (Drd1, Drd2) was detected in BTBR mice in the postnatal period of ontogenesis mainly in the frontal cortex, while in the hippocampus of mature mice (p60), only a decrease in the Drd2 mRNA level was revealed. The obtained results suggest that the decrease in the expression levels of CDNF, BDNF-TrkB and dopamine receptors in the frontal cortex in the postnatal period can lead to significant changes in both the morphology of neurons and dopamine neurotransmission in cortical brain structures. At the same time, the increase in p75NTR receptor gene expression observed on the 14th day of embryogenesis, crucial for hippocampus and frontal cortex development, may have direct relevance to the manifestation of early autism.

Purinosomes and Purine Metabolism in Mammalian Neural Development: A Review.

Neural stem/progenitor cells (NSPCs) in specific brain regions require precisely regulated metabolite production during critical development periods. Purines-vital components of DNA, RNA, and energy carriers like ATP and GTP-are crucial metabolites in brain development. Purine levels are tightly controlled through two pathways: de novo synthesis and salvage synthesis. Enzymes driving de novo pathway are assembled into a large multienzyme complex termed the "purinosome." Here, we review purine metabolism and purinosomes as spatiotemporal regulators of neural development. Notably, around postnatal day 0 (P0) during mouse cortical development, purine synthesis transitions from the de novo pathway to the salvage pathway. Inhibiting the de novo pathway affects mTORC1 pathway and leads to specific forebrain malformations. In this review, we also explore the importance of protein-protein interactions of a newly identified NSPC protein-NACHT and WD repeat domain-containing 1 (Nwd1)-in purinosome formation. Reduced Nwd1 expression disrupts purinosome formation, impacting NSPC proliferation and neuronal migration, resulting in periventricular heterotopia. Nwd1 interacts directly with phosphoribosylaminoimidazole-succinocarboxamide synthetase (PAICS), an enzyme involved in de novo purine synthesis. We anticipate this review will be valuable for researchers investigating neural development, purine metabolism, and protein-protein interactions.

Adolescents’ short-form video addiction and sleep quality: the mediating role of social anxiety

BackgroundAdolescence is a critical period for individual growth and development. Insufficient sleep adversely affects adolescents’ physical development, blood pressure, vision, and cognitive function. This study examined the effect of short-form video addiction on adolescents’ sleep quality, as well as the mediating role of social anxiety, to identify methods for improving adolescents’ sleep quality in the Internet era.MethodsA questionnaire survey was conducted in this cross-sectional study on 1629 adolescents recruited from three high schools. Their short-form video addiction, social anxiety, and sleep quality were evaluated using corresponding scales. Pearson correlation analysis was carried out to analyze the relationships among short‐form video addiction, sleep quality, and social anxiety. Mediating effect analysis was constructed using AMOS 20.0 statistical software.ResultsParticipants’ sleep quality score is 6.12 ± 3.29 points. The detection rate of sleep quality among them is 31.06%. Short‐form video addiction, sleep quality, and social anxiety are significantly correlated (r = 0.439, 0.404, 0.457, P < 0.001). The direct effect of short-form video addiction on sleep quality is 0.248, accounting for 62.4% of the total effect. The indirect effect exerted through social anxiety is 0.149, accounting for 37.6%.ConclusionsSleep disorders are very common among Chinese adolescents. Short‐form video addiction is positively correlated with adolescents’ sleep quality and social anxiety. Social anxiety partially mediates the relationship between short-form video addiction and sleep quality. The adverse effects of short-form video addiction and social anxiety on the sleep quality of this group must be minimized. Schools are recommended to implement measures to promote sleep quality among adolescents.

Parents and caregivers as key players in the prevention and identification of body image concerns and eating disorders among early adolescents

ABSTRACT Early adolescence (ages 11–14 years) is a key period for the emergence of body image and eating concerns, and early identification and access to treatment are imperative for positive outcomes. Despite research identifying this critical developmental period, few prevention resources are available for early adolescents. Parents are key players for this age group and important socializing agents. As such, they are well positioned to help youth access resources or support where needed. However, programs to position and involve parents as interventionists are lacking. Our aims are two-fold. First, we review the evidence for the effectiveness of parents as body image interventionists and the existing data regarding parental needs. Second, we provide directions for future research and outline a framework for empowering parents as interventionists, identifying key domains in which parents may play a role in addressing body image and eating concerns among early adolescents. Based on the extent literature, these domains include facilitating engagement with or co-utilizing intervention content to decrease body image and eating concerns in at-risk children, which may also help to increase parents’ effectiveness in their efforts to support youth. In addition, parents may deliver content to decrease or reverse risk-factors and early symptoms, or disrupt the early disorder phase of illness. To date, parents constitute an underutilized resource in eating disorder and disordered eating prevention, and efforts should be made to increase the evidence-based strategies to leverage their relationship with at-risk children.

A site-wise reliability analysis of the ABCD diffusion fractional anisotropy and cortical thickness: impact of scanner platforms.

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce non-biological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation coefficients (ICC). We developed a site-wise adaptive ICC (AICC) to evaluate the reliability of imaging-derived phenotypes while accounting for ongoing brain development. AICC iteratively estimates the population-level age-related brain development trajectory using a weighted mixed model and updates age-corrected site-wise reliability until convergence. We evaluated the test-retest reliability of regional fractional anisotropy (FA) measures from diffusion tensor imaging and cortical thickness (CT) from structural MRI data for each site. The mean AICC for 20 FA tracts across sites was 0.61±0.19, lower than the mean AICC for CT in 34 regions across sites, 0.76±0.12. Remarkably, sites using Siemens scanners consistently showed significantly higher AICC values compared to those using GE/Philips scanners for both FA (AICC=0.71±0.12 vs 0.46±0.17, p<0.001) and CT (AICC=0.80±0.10 vs 0.69±0.11, p<0.001). These findings demonstrate site-and-scanner related variations in data quality and underscore the necessity for meticulous data curation in subsequent association analyses.

Developmental hearing loss–induced perceptual deficits are rescued by genetic restoration of cortical inhibition

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.