Developmental Course Research Articles

Phoneme Awareness Predicts Character Reading Ability in Young Chinese Children Through Phonemic Mismatch Negativity

The current literature suggests mixed findings regarding the relationship between visual spatial skill and Chinese reading ability. In this longitudinal study, 106 kindergarteners in Hong Kong were tested on visual spatial skill and Chinese character reading ability in their first, second, and third years of kindergarten (K1, K2, and K3) with 12-month intervals between the three testing points. Cross-lagged path analysis showed a bidirectional relationship between visual spatial skill and Chinese character reading ability from K1 to K2. Children's visual spatial skill in K1 predicted their reading ability in K2 (B = 0.35, SE = 0.17, p < .05, β = .17), and their reading ability in K1 explained the unique variance of visual spatial skill measured in K2 (B = 0.29, SE = 0.12, p < .05, β = .25). In total, it explained 19.4% (p < .01) and 35.8% (p < .001) variance of visual spatial skill at T2 and reading ability at T2. However, the bidirectional relationship diminished between K2 and K3. The results demonstrate the developmental course of the relationship between visual spatial skill and reading ability as well as the reciprocal facilitation of the two skills in the beginning phase of reading development but not later phases.

Neuromuscular Diseases Affect Number Representation and Processing: An Exploratory Study.

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) both are rare genetic neuromuscular diseases with progressive loss of motor ability. The neuromotor developmental course of those diseases is well documented. In contrast, there is only little evidence about characteristics of general and specific cognitive development. In both conditions the final motor outcome is characterized by an inability to move autonomously: children with SMA never accomplish independent motoric exploration of their environment, while children with DMD do but later lose this ability again. These profound differences in developmental pathways might affect cognitive development of SMA vs. DMD children, as cognition is shaped by individual motor experiences. DMD patients show impaired executive functions, working memory, and verbal IQ, whereas only motor ability seems to be impaired in SMA. Advanced cognitive capacity in SMA may serve as a compensatory mechanism for achieving in education, career progression, and social satisfaction. This study aimed to relate differences in basic numerical concepts and arithmetic achievement in SMA and DMD patients to differences in their motor development and resulting sensorimotor and environmental experiences. Horizontal and vertical spatial-numerical associations were explored in SMA/DMD children ranging between 6 and 12 years through the random number generation task. Furthermore, arithmetic skills as well as general cognitive ability were assessed. Groups differed in spatial number processing as well as in arithmetic and domain-general cognitive functions. Children with SMA showed no horizontal and even reversed vertical spatial-numerical associations. Children with DMD on the other hand revealed patterns in spatial numerical associations comparable to healthy developing children. From the embodied Cognition perspective, early sensorimotor experience does play a role in development of mental number representations. However, it remains open whether and how this becomes relevant for the acquisition of higher order cognitive and arithmetic skills.

Prenatal auditory learning in avian vocal learners and non-learners.

Understanding when learning begins is critical for identifying the factors that shape both the developmental course and the function of information acquisition. Until recently, sufficient development of the neural substrates for any sort of vocal learning to begin in songbirds was thought to be reached well after hatching. New research shows that embryonic gene activation and the outcome of vocal learning can be modulated by sound exposure in ovo. We tested whether avian embryos across lineages differ in their auditory response strength and sound learning in ovo, which we studied in vocal learning (Maluridae, Geospizidae) and vocal non-learning (Phasianidae, Spheniscidae) taxa. While measuring heart rate in ovo, we exposed embryos to (i) conspecific or heterospecific vocalizations, to determine their response strength, and (ii) conspecific vocalizations repeatedly, to quantify cardiac habituation, a form of non-associative learning. Response strength towards conspecific vocalizations was greater in two species with vocal production learning compared to two species without. Response patterns consistent with non-associative auditory learning occurred in all species. Our results demonstrate a capacity to perceive and learn to recognize sounds in ovo, as evidenced by habituation, even in species that were previously assumed to have little, if any, vocal production learning.This article is part of the theme issue ‘Vocal learning in animals and humans’.

Socioeconomic origin, future expectations, and educational achievement: A longitudinal three-generation study of the persistence of family advantage.

Expectations about the future direct effort in goal-oriented action and may influence a range of life course outcomes, including educational attainment. Here we investigate whether such expectations are implicated in the dynamics underlying the persistence of educational advantage across family generations, and whether such dynamics have changed in recent decades in view of historical change. Focusing on the role of domain-specific (educational) and general (optimism and control) expectations, we examine parallels across parent-child cohorts in (a) the relationships between parental socioeconomic status (SES) and children's future expectations and (b) the associations between children's future expectations and their academic achievement. We estimate structural equation models using data from the prospective multigenerational Youth Development Study (N = 422 three-generation triads [G1-G2-G3]; G1 Mage in 1988 = 41.0 years, G2 Mage in 1989 = 14.7 years, G3 Mage in 2011 = 15.8 years; G2 White in 1989 = 66.4%, G3 White in 2011 = 64.4%; G1 mean annual household income, converted to 2008 equivalents = $41,687, G2 mean annual household income in 2008 dollars = $42,962; G1 mode of educational attainment = high school, G2 mode of educational attainment = some college). We find intergenerational similarity in the relationships between parental educational attainment and children's future expectations. Children's educational expectations strongly predicted their academic achievement in the second generation, but not in the third generation. With educational expansion, the more recent cohort had higher educational expectations that were less strongly related to achievement. Overall, the findings reveal dynamics underlying the persistence of educational success across generations. The role of future expectations in this intergenerational process varies across historical time, confirming a central conclusion of life span developmental psychology and life course sociological research that individual functioning is influenced by sociocultural contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Does the Method of Acceleration Matter? Exploring the Likelihood of College Coursetaking Success Across Four Developmental Education Instructional Strategies

Background/Context: Accelerated instructional strategies for developmental education have been promoted as a way to help underprepared students to progress more quickly through college-level coursework. Yet, what remains unknown is whether certain accelerated strategies are more effective than others and whether this initial acceleration may lead to longer term success. Purpose/Objective/Research Question/Focus of Study: We examine whether the likelihood of success varies for completion of mathematics and English requirements over 3 years among the Florida students enrolled in courses using one of four developmental instructional strategies: compressed, corequisite, modularized, or contextualized. Population/Participants/Subjects: Our sample includes all first-time-in-college students during the 2015–2016 year who enrolled in all 28 public state colleges and took any developmental education course during the first year. Research Design: We use inverse probability-weighted regression adjustment (IPWRA) to compare success rates in completion of mathematics and English requirements over 3 years for Florida college students in each of these strategies. Findings/Results: Overall, the results demonstrate variation in the likelihood of success for completion of mathematics and English courses over 3 years among students in different developmental instructional strategies, which suggests that the method of acceleration does matter. Corequisite courses tended to lead to greater long-term gains in math and, to an extent, in reading, while contextualized tended to be most effective in writing. Conclusions/Recommendations: Leaders can play an important role in strengthening institutional capacity to effectively implement developmental education reform by developing faculty buy-in, ensuring adequate resources to scale and sustain reform efforts, and using data to inform future decision-making.

Adopting Online Learning in College Developmental Education Coursework: Impact on Course Persistence, Completion, and Subsequent Success

ABSTRACT Online learning has been increasing rapidly at community colleges, especially in low-division high-demand coursework, such as developmental education. While existing studies have identified negative effects associated with online instruction in semester-long coursework in this particular setting, there is less evidence about how distance learning influences students’ completion of developmental education coursework and, more importantly, their subsequent academic outcomes. This paper examines the impact of fully online instruction, compared with traditional face-to-face instruction, on both concurrent developmental course outcomes and downstream outcomes. We use an administrative dataset from a state community college system that includes longitudinal student-unit record data from more than 40,000 students enrolled in developmental education courses between 2005 and 2012, and employ a two-way fixed effects model that controls for selection both at the course- and student-level. We find that taking one’s first developmental course through the online format reduces developmental course completion rate by 13 percentage points and subsequent enrollment in the gatekeeper course by 7 percentage points. Successful completion of developmental and subsequent gateway coursework represents critical milestones among community college students. This paper provides insight on how delivery format influences both the concurrent and downstream outcomes of developmental education students.

Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index.

The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.

Polypharmacy trajectories among older women with and without dementia: A longitudinal cohort study

BackgroundAlthough multiple medications are often utilized to achieve optimal treatment outcomes, polypharmacy (use of five or more medications) among older population is associated with several detrimental effects. Trajectories of polypharmacy among older population over time has not been described. ObjectiveThis study estimated polypharmacy prevalence and clusters of individuals with similar patterns of change in polypharmacy among a cohort of older Australian women with and without dementia. MethodLongitudinal prospective cohort data from the oldest birth cohort (1921–1926) of the Australian Longitudinal Study on women's Health (ALSWH) were analysed. Survey data were linked with Pharmaceutical Benefit Schemes (PBS) data to obtain information about the type and number of prescription medications for each year 2003–2015. Group based trajectory modelling was used to identify distinct trajectory groups, based on the presence of polypharmacy for each year of observation. Trajectories were named based on distinctive and meaningful subgroups that followed approximately the same developmental course and probability assignment rule. Generalized estimating equation was used to identify factors associated with polypharmacy. ResultsA total of 10,372 women were eligible for the inclusion in the study. Prevalence of polypharmacy increased over time and reached as high as 71.19% and 71.29% in 2014 for women with and without dementia, respectively. Four distinct polypharmacy trajectories were identified: ‘Consistent Polypharmacy’ (55.88%);‘Low Polypharmacy’ (24.52%); ‘Rapid Increasing Polypharmacy’ (12.50%); and ‘Moderate Polypharmacy’ (7.12%). Dementia, Residential Aged Care (RAC), frailty and comorbid condition were the key drivers of polypharmacy in this cohort. ConclusionThe prevalence of polypharmacy among older women increased over time, with most women have a pattern of consistent polypharmacy or rapidly increasing polypharmacy. Appropriate, sustainable, and effective strategies for reducing medication use should be implemented for women as they age, and particularly for those with dementia and those in residential care.

Inter-individual variability in structural brain development from late childhood to young adulthood

A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined inter-individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0–26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable inter-individual variability in the magnitude of changes observed for all examined brain measures. The majority of individuals demonstrated decreases in total gray matter volume, cortex volume, mean cortical thickness, and white matter surface area in mid-adolescence, with more variability present during the transition into adolescence and the transition into early adulthood. While most individuals demonstrated increases in white matter volume in early adolescence, this shifted to a majority demonstrating stability starting in mid-to-late adolescence. We observed sex differences in these patterns, and also an association between the size of an individual's brain structure and the overall rate of change for the structure. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.

Deriving within-person estimates of delta-beta coupling: A novel measure for identifying individual differences in emotion and neural function in childhood.

Delta-beta coupling is increasingly used to understand early emotional development. However, little is known about the development of the coupling, limiting its utility for identifying normative or aberrant functioning. We used a prospective longitudinal sample (N=122) to compare measures of within-person and between-person coupling between ages 3 and 5, track the developmental trajectory of coupling, identify individual differences in patterns of development, and explore emotion-related predictors and outcomes of discrete developmental patterns. Within-person measures, limited in overall utility, were most useful when (1) statistical approaches produced more homogenous groups within the overall sample (extreme groups or latent classes) or (2) the full developmental course was considered. We found two trajectories of change in frontal coupling and three trajectories of change in parietal coupling. Coupling trajectories were predicted by observed fear and approach/avoidance at age 3. In addition, high levels of frontal coupling at age 3 that declined and then levelled out through age 5 were associated with lower levels of internalizing by age 5. This work provides a foundation for understanding normative change in delta-beta coupling across the preschool years and useful insight for the use of this metric in future work.

Defining Dravet syndrome: An essential pre-requisite for precision medicine trials.

ObjectiveThe classical description of Dravet syndrome, the prototypic developmental and epileptic encephalopathy, is of a normal 6‐month‐old infant presenting with a prolonged, febrile, hemiclonic seizure and showing developmental slowing after age 1 year. SCN1A pathogenic variants are found in >80% of patients. Many patients have atypical features resulting in diagnostic delay and inappropriate therapy. We aimed to provide an evidence‐based definition of SCN1A‐Dravet syndrome in readiness for precision medicine trials.MethodsEpilepsy patients were recruited to the University of Melbourne Epilepsy Genetics Research Program between 1995 and 2020 by neurologists from around the world. Patients with SCN1A pathogenic variants were reviewed and only those with Dravet syndrome were included. Clinical data, including seizure and developmental course, were analyzed in all patients with SCN1A‐Dravet syndrome.ResultsTwo hundred and five patients were studied at a median age of 8.5 years (range 10 months to 60 years); 25 were deceased. The median seizure‐onset age was 5.7 months (range 1.5–20.6 months). Initial seizures were tonic‐clonic (52%) and hemiclonic (35%), with only 55% being associated with fever. Only 34% of patients presented with status epilepticus (seizure lasting ≥30 minutes). Median time between first and second seizure was 30 days (range 4 hours to 8 months), and seven patients (5%) had at least 6 months between initial seizures. Median ages at onset of second and third seizure types were 9.1 months (range 3 months–25.4 years) and 15.5 months (range 4 months–8.2 years), respectively. Developmental slowing occurred prior to 12 months in 27%.SignificanceAn evidence‐based definition of SCN1A‐Dravet syndrome is essential for early diagnosis. We refine the spectrum of Dravet syndrome, based on patterns of seizure onset, type, and progression. Understanding of the full spectrum of SCN1A‐Dravet syndrome presentation is essential for early diagnosis and optimization of treatment, especially as precision medicine trials become available.

Change in Juvenile Offending Versatility Predicted by Individual, Familial, and Environmental Risks

Developmental and life-course criminology elucidate the developmental course and change of antisociality over time, considering that longitudinal trajectories differ. Specific relations between risks and different antisociality outcomes are emphasized. We assume that adolescents have different longitudinal trajectories considering the change of offending over time and that risks contribute variably to offending pathways. The current study is based on a German research project in which adolescents (N = 577) were interviewed in two German cities. Based on self-reported crime data, we utilized the slope values of offending versatility (OV) over time as outcome values in regression mixture models capturing the trends for participants over age and exhibiting two components of offending adolescents. We explored the contribution of different risks to OV, defining specific risk patterns: Acceptance of violence and peer delinquency have significant negative effects on the emergence of OV within the group of adolescents with decreasing OV. Acceptance of violence has a significant negative effect, and corporal punishment has a significant positive effect on the emergence of OV within the group of adolescents with increasing or rather stable OV. The results underline the relevance of the violence-related risk factor corporal punishment for the emergence of OV within the last-mentioned group.

The developmental course of the link between weight concerns and cigarette use across adolescence: Differences by gender.

This study aimed to illuminate developmental changes and gender differences in the link between weight concerns and cigarette use across adolescence. Specifically, we examined whether and how the strength of the association between weight concerns and cigarette use changed across adolescence, and whether patterns of association differed between boys and girls. Participants were 397 predominately White adolescents ages 11-18 years (50.5% female) from a longitudinal observational study conducted in the United States. Time-varying effect modeling revealed that even after adjusting for BMI, the association between weight concerns and cigarette use was positive and significant for girls from age 11.3 to 15.9, with the strongest association at 12.7 years. For boys, this association was non-significant throughout adolescence. Results suggest a sensitive period in early- to mid-adolescence during which girls with weight concerns may be at heightened risk for cigarette use. Findings have implications for the developmental timing of interventions to prevent cigarette use and weight concerns and suggest that tailored interventions for girls may be warranted.

The development of allocentric spatial frame in the auditory system

The ability to encode space is a crucial aspect of interacting with the external world. Therefore, this ability appears to be fundamental for the correct development of the capacity to integrate different spatial reference frames. The spatial reference frame seems to be present in all the sensory modalities. However, it has been demonstrated that different sensory modalities follow various developmental courses. Nevertheless, to date these courses have been investigated only in people with sensory impairments, where there is a possible bias due to compensatory strategies and it is complicated to assess the exact age when these skills emerge. For these reasons, we investigated the development of the allocentric frame in the auditory domain in a group of typically developing children aged 6–10 years. To do so, we used an auditory Simon task, a paradigm that involves implicit spatial processing, and we asked children to perform the task in both the uncrossed and crossed hands postures. We demonstrated that the crossed hands posture affected the performance only in younger children (6–7 years), whereas at 10 years of age children performed as adults and were not affected by such posture. Moreover, we found that this task’s performance correlated with age and developmental differences in spatial abilities. Our results support the hypothesis that auditory spatial cognition’s developmental course is similar to the visual modality development as reported in the literature.

Integrative Science Approach to Resilience: The Notre Dame Study of Health & Well-being (NDHWB)

Although many studies have unequivocally demonstrated the promise of understanding resilience to adversity and characterizing the consequences if stress is unabated, needed are dynamic theories and methods to enhance the rigor and interpretation of these assessments. From a dynamic systems perspective, the focus is not whether an individual possesses some fixed ability or unchangeable trait, but rather to understand the flexibility and responsiveness of stress regulation systems to daily hassles and adverse life events. A renewed interest in individual variability allows researchers to see trajectories of change over both short- and long-time scales to understand the developmental course. As a result, it is possible to answer questions, such as, how does the dysregulation in emotion caused by stress, to both within and between daily affect processes, relate to longitudinal trajectories (over time-scales of years) of dysfunction and disease? The overarching goal of the Notre Dame Study of Health & Well-being is to detail the types and qualities of contextual influences, in conjunction with dynamic psychobiological systems, to assess the precursors, concomitant influences and consequences of stress and resilience in the face of adversity on cognitive, health, and well-being outcomes.

Caregivers' Burden of School-Aged Children with Neurodevelopmental Disorders: Implications for Family-Centred Care.

Caregivers of children with neurodevelopmental disorders play a central role during the rehabilitation and education processes, but they have an increasing risk of psychosocial problems even if the literature is not so agreed upon the specific and predisposing factors to that. The aim of this study was to examine possibly differences of burden levels in an Italian sample of principal caregivers of children with different kinds of neurodevelopmental disorders and to investigate the possible links between some clinical and sociodemographic variables and the levels of caregiver’s burden. 105 caregivers of school-aged children with neurodevelopmental disorders were included in the study and completed three online questionnaires (General Questionnaire, Caregiver Burden Inventory, Zarit Caregiver Burden Scale). Results highlighted that about the half of caregivers show from moderate to high levels of stress, but parents of children with Autism Spectrum Disorder and Intellectual Disability show greater difficulties than parents of children with Attention-Deficit Hyperactivity Disorder, Language and/or Learning Disorder, and Developmental Coordination Disorder. Moreover, it was evident a negative correlation between the burden levels and the age of children, but also a direct correlation between the burden levels and the weekly hours of rehabilitation. These findings show that severity of caregiver’s burden is dependent by the type of neurodevelopmental disorder and suggest that an ecological and family-centred approach is necessary to guarantee the life health developmental course of these children.

Integration of 1:1 orthology maps and updated datasets into Echinobase.

Echinobase (https://echinobase.org) is a central online platform that generates, manages and hosts genomic data relevant to echinoderm research. While the resource primarily serves the echinoderm research community, the recent release of an excellent quality genome for the frequently studied purple sea urchin (Strongylocentrotus purpuratus genome, v5.0) has provided an opportunity to adapt to the needs of a broader research community across other model systems. To this end, establishing pipelines to identify orthologous genes between echinoderms and other species has become a priority in many contexts including nomenclature, linking to data in other model organisms, and in internal functionality where data gathered in one hosted species can be associated with genes in other hosted echinoderms. This paper describes the orthology pipelines currently employed by Echinobase and how orthology data are processed to yield 1:1 ortholog mappings between a variety of echinoderms and other model taxa. We also describe functions of interest that have recently been included on the resource, including an updated developmental time course for S.purpuratus, and additional tracks for genome browsing. These data enhancements will increase the accessibility of the resource to non-echinoderm researchers and simultaneously expand the data quality and quantity available to core Echinobase users. Database URL: https://echinobase.org

Embracing e-service learning in the age of COVID and beyond.

The COVID-19 pandemic has challenged educators in numerous ways. One particular area of challenge has been the inability of students to go to traditional service learning sites. The present article explores electronic service learning, which focuses on service-learning opportunities that do not require face-to-face interaction with community partners, and provides two examples of alternative service-learning assignments used in a developmental psychology course. Eighteen students enrolled in an upper-level course on child development engaged with course material and empirical articles to understand the content of various children's books or to create educational videos for children. A library of storybook recordings and electronic videos produced by the students was then shared with a local nonprofit organization's preschool teachers to use in their classrooms. Students reported very positive experiences with these assignments and highlighted the benefits of electronic service learning, in particular. This assignment could easily be adapted to other courses within psychology and some examples are described. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Relations between intensionality, theory of mind and complex syntax in autism spectrum conditions and typical development

False belief (FB) reasoning emerges around 4−5 years of age in typical development (TD), but has an extended developmental course in children with autism spectrum conditions (ASC). A body of work suggests that this capacity is related to the comprehension of embedded clauses, as in Children think/say that fairies exist. The development of other metarepresentational capacities, such as thinking about the same objects under different descriptions (‘intensionality’), has been much less studied, particularly in ASC, and its links both to embedding and FB remain to be determined. Here we aimed to study belief-reasoning, intensionality and embedded clause comprehension in conjunction. An additional aim was to compare performance across different types of embedded clauses, specifically relative clauses and three types of complement clauses (embedded under ‘says that’, ‘sees that’ and ‘seems that’, respectively), and to test their predictive relations to metarepresentational abilities. Twenty-five children and early adolescents with ASC (mean age 9;4) as well as a group of twenty-five children with TD, matched on both chronological and verbal mental age (VMA, mean 9;1), were recruited. A maximally analogous picture-matching design was used across all tasks. Results of a series of logistic mixed effect models revealed greater vulnerability in ASC on both metarepresentational tasks (ToM and intensionality) indiscriminately, and within the domain of embedding, on ‘seems that’. Scores on embedding predicted performance on metarepresentation, as did those on Seems that. A pervasive main effect of VMA was seen in all models. These results show that metarepresentational impairments in ASC extend to intensionality and relate to language development, where syntactic construction types referencing appearances prove to be particularly challenging in ASC and TD alike.

Sensitive period for rescuing parvalbumin interneurons connectivity and social behavior deficits caused by TSC1 loss

The Mechanistic Target Of Rapamycin Complex 1 (mTORC1) pathway controls several aspects of neuronal development. Mutations in regulators of mTORC1, such as Tsc1 and Tsc2, lead to neurodevelopmental disorders associated with autism, intellectual disabilities and epilepsy. The correct development of inhibitory interneurons is crucial for functional circuits. In particular, the axonal arborisation and synapse density of parvalbumin (PV)-positive GABAergic interneurons change in the postnatal brain. How and whether mTORC1 signaling affects PV cell development is unknown. Here, we show that Tsc1 haploinsufficiency causes a premature increase in terminal axonal branching and bouton density formed by mutant PV cells, followed by a loss of perisomatic innervation in adult mice. PV cell-restricted Tsc1 haploinsufficient and knockout mice show deficits in social behavior. Finally, we identify a sensitive period during the third postnatal week during which treatment with the mTOR inhibitor Rapamycin rescues deficits in both PV cell innervation and social behavior in adult conditional haploinsufficient mice. Our findings reveal a role of mTORC1 signaling in the regulation of the developmental time course and maintenance of cortical PV cell connectivity and support a mechanistic basis for the targeted rescue of autism-related behaviors in disorders associated with deregulated mTORC1 signaling.