Developmental Neuroscience最新文献

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.

Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.

Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.

Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.

Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.

Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.

Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

Introduction: Neuropsychiatric symptoms following SARS-CoV-2 infection have been described in a substantial proportion of patients, acute, subacute, and chronic. Understanding of the neurological and neuropsychiatric sequelae of this virus is an emerging field of study with rapidly evolving descriptions of its impact on the central and peripheral nervous system.

Case presentation: Here, we report a series of 8 pediatric patients presenting with acute onset neuropsychiatric symptoms following SARS-CoV-2 infection who received comprehensive medical and psychiatric evaluation and treatment in our research-based Neuroimmune Psychiatric Disorders Program. We provide a review of the research available to date regarding potential mechanisms underlying neuroinflammatory consequences of this endemic infection. Opportunities for further investigations of mechanisms, evaluations and impactful treatments following SARS-CoV-2 infection are described.

Conclusion: The pediatric cases presented share acute onset of obsessive-compulsive disorder, psychosis, tics, neurobehavioral and physiological symptoms, with significant response to treatments targeting inflammation in combination with psychiatric and psychological interventions. Ongoing study and identification of this phenomenon of abrupt neuropsychiatric changes following SARS-CoV-2 infection may lead to more effective treatments with potential application to broader populations.

Introduction: Homeobox genes are highly conserved and play critical roles in brain development. Recently, we have found that mammals have an additional fragment of approximately 20 amino acids in Emx1 and a poly-(AL)_6-7 in Emx2, compared to other amniotes. It has been shown that Emx1 and Emx2 have synergistic actions in the brain development. These reports raise an interesting issue whether the differences of Emx1 and Emx2 between mammals and non-mammals are concerned with the organization and evolution of amniote pallium.

Methods: Lentiviruses expressing mouse Emx1 and Emx2 (mEmx1/2) with additional fragments were injected into the ventricle of the chick telencephalon at embryonic day 3 to study the effects of mEmx1/2 on the development of chick pallium, whereas injections of lentiviruses containing chick Emx1 and Emx2 (cEmx1/2), no targeted gene insert or saline were as controls. The expressions of reelin, vimentin, GABA and MAP2, neurogenesis patterns for calbindin (CB) and parvalbumin (PV) neurons and the sizes of anterior commissure (AC) were then studied by immuohistochemical staining, and open-field tests were performed to assess locomotor activities and curious or exploratory behaviors of the chicks.

Results: Following the injections of lentiviruses expressing mEmx1/2, the expressions of reelin, vimentin, GABA, and MAP2 increased in most parts of Wulst (W) and mesopallium (M), but not most of nidopallium (N). Neurogenesis patterns for CB and PV neurons changed toward mammalian inside-out one, and the sizes of AC staining for neurofilament were significantly larger. In addition, post-hatchling chicks showed higher rates of passive avoidance after training, but no significant differences in the total distance traveled and the percentage of time spent in the central rectangle, compared to those in the control groups.

Conclusion: The present study indicated that mEmx1/2 had effects on the development of chick pallium, suggesting that they are probably involved in the organization and evolution of amniote pallium.

Background: Fetal growth restriction (FGR) corresponds to the fetus's inability to achieve an adequate weight gain based on genetic potential and gestational age. It is an important cause of morbidity and mortality.

Summary: In this review, we address the challenges of diagnosis and classification of FGR. We review how chronic fetal hypoxia impacts brain development. We describe recent advances on placental and fetal brain imaging using magnetic resonance imaging and how they offer new noninvasive means to study growth restriction in humans. We go on to review the impact of FGR on brain integrity in the neonatal period, later childhood, and adulthood and review available therapies.

Key messages: FGR consequences are not limited to the perinatal period. We hypothesize that impaired brain reserve, as defined by structure and size, may predict some concerning epidemiological data of impaired cognitive outcomes and dementia with aging in this group of patients.

Background: Fetal growth restriction (FGR) corresponds to the fetus's inability to achieve an adequate weight gain based on genetic potential and gestational age. It is an important cause of morbidity and mortality.

Summary: In this review, we address the challenges of diagnosis and classification of FGR. We review how chronic fetal hypoxia impacts brain development. We describe recent advances on placental and fetal brain imaging using magnetic resonance imaging and how they offer new noninvasive means to study growth restriction in humans. We go on to review the impact of FGR on brain integrity in the neonatal period, later childhood, and adulthood and review available therapies.

Key messages: FGR consequences are not limited to the perinatal period. We hypothesize that impaired brain reserve, as defined by structure and size, may predict some concerning epidemiological data of impaired cognitive outcomes and dementia with aging in this group of patients.

Introduction: Early prediction and timely intervention are particularly essential for high-risk preterm infants. Brain magnetic resonance imaging (BMRI) is frequently used alongside functional evaluations to improve predictions of developmental outcomes. This study aimed to assess voxel-based brain volumetry in extremely preterm infants using BMRI at term equivalent age (TEA) and investigate its association with developmental outcomes.

Methods: From March 2016 to December 2019, high-risk preterm infants (birth weight <1,500 g or gestational age <32 weeks) with BMRI at TEA and follow-up developmental data assessed by Bayley-III were included. For BMRI volumetry, manual tracing and segmentation were performed on T1-weighted scans, and after smoothing, voxels were calculated for each brain segment. Forty-seven subjects were enrolled and categorized into typical/delayed motor groups.

Results: Results revealed a significant difference in ventricle size and ventricle ratio in BMRI at TEA between the groups. Even after controlling for other factors that could influence developmental outcomes, ventricle ratio emerged as a robust, single predictor for future motor development.

Conclusion: This study suggests the potential clinical utility of BMRI volumetry in predicting motor development outcomes.

Introduction: Obsessive-compulsive disorder (OCD) is a mental health disorder characterized by obsessions and compulsions. There is a mounting body of evidence suggesting a link between OCD and inflammation. Neuropsychiatric deteriorations have been reported to follow COVID-19 infections, including OCD. Additionally, symptomatic arthritis has also been reported following COVID-19 infection. We aim to describe post-COVID-19 clinical deteriorations presenting to our multidisciplinary immune behavioral health clinic.

Methods: One hundred and fifty-one prescreened patients were evaluated in our clinic between March 1, 2020 and August 1, 2024. We systematically searched charts for infection with SARS-CoV-2 and found 3 cases of confirmed COVID-19 infection that preceded an abrupt neuropsychiatric deterioration (in the absence of other detected infections). Per our clinic's latest protocol, all patients underwent a full rheumatology and arthritis evaluation (regardless of joint complaints) including ultrasound imaging, which were used to objectively assess for effusions, synovitis, and capsulitis.

Results: Two of the three patients met criteria for a PANS diagnosis. All 3 patients had new-onset OCD or reescalation of OCD with new obsessions/compulsions/rituals post-COVID-19 and all three had imaging findings of effusions +/- synovitis +/- capsulitis despite not having significant complaints of joint pain. Joint pain complaints evolved after psychiatric symptoms improved (because the capacity of the patient to articulate joint pain improved when they were less overwhelmed by intrusive thoughts). Immunomodulatory treatment began with nonsteroidal anti-inflammatory drugs (NSAIDs) and was escalated to disease-modifying antirheumatic drugs (DMARDs) in the 2 patients with synovitis +/- capsulitis. All 3 patients eventually returned to baseline neuropsychiatric health (minimal-to-no OCD and resolution of intense anxiety and mood instability) and also had improvement in arthritic findings after introduction of NSAID +/- DMARDs.

Conclusion: Infections may result in systemic immune activation leading to inflammation. Thus, when patients have an acute neuropsychiatric deterioration (hypothesized to have been triggered by an infection), the situation may warrant evaluation for inflammation in other more accessible sites (e.g., joints). Use of this evidence of inflammation (as a sign of immune activation) is helpful since it is difficult to assess for brain inflammation, as clinical brain imaging has poor sensitivity for inflammation and biopsy of the striatum (and other areas involved in OCD) is difficult and limited by risk. In our cases, early joint imaging not only helped confirm signs of systemic inflammation in the setting of neuropsychiatric symptoms, but it also allowed for earlier initiation of immunomodulatory treatment.

Background: In contemporary medical practice, general anesthesia plays an essential role in pediatric surgical procedures. While modern anesthetic protocols have demonstrated safety and efficacy across various pathological conditions, concerns persist regarding the potential neurotoxic effects associated with early exposure to general anesthesia.

Summary: Current research primarily examines the neurocognitive developmental impacts, with limited focus on neurobehavioral developmental disorders. This review presents a comprehensive analysis of clinical trial results related to five critical neurobehavioral developmental disorders: fine motor disability, attention-deficit hyperactivity disorder, impulse control disorders, autism spectrum disorder, and developmental coordination disorder. Furthermore, this review synthesizes insights from basic research on the potential toxicological mechanisms of general anesthetic agents that could influence clinical neurobehavioral changes. These findings provide valuable guidance for the prudent and safe utilization of anesthetic agents in pediatric patients.

Key messages: This review explores the potential connections between general anesthesia and five neurobehavioral disorders, highlighting the importance of cautious anesthetic use in children in light of current research findings.

Introduction: Pediatric acute-onset neuropsychiatric syndrome (PANS) is an immune-mediated disease characterized by abrupt onset neurobehavioral changes. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), chronic conditions characterized by gastrointestinal inflammation. We describe eight individuals with both PANS and IBD.

Methods: All individuals with both IBD and PANS were identified from Stanford Immune Behavioral Health Clinic, Cedars-Sinai Medical Center Pediatric Inflammatory Bowel Disease Program, and Dartmouth Neuroimmune Psychiatric Disorders (NIPD) Clinic. Data were collected by chart review.

Results: Eight cases of PANS with IBD were identified. Five were male. The mean age of onset was 9.3 years for PANS and 15.6 years for IBD. PANS preceded development of IBD in 7 of 8 cases by a mean of 8.4 years. Seven patients (88%) had a first-degree relative with an immune-mediated disease, including 5 with psoriasis or psoriatic arthritis. Five patients themselves had arthralgias or arthritis (63%). All 5 cases where PANS preceded IBD treatment sufficiently for analysis were free of major behavioral relapses after IBD was managed.

Conclusion: The triad of PANS, joint complaints, and family history of autoimmunity, including psoriasis, may represent a subset of PANS at heightened risk for IBD and additional immune-mediated disorders. For children with this triad, clinicians should have a low threshold to evaluate for gastrointestinal inflammation with biomarkers like hemoglobin, CRP, fecal calprotectin, and diagnostic endoscopy when indicated. PANS symptoms may improve with effective treatment of IBD. The high prevalence of joint complaints in our cohort and psoriasis in first-degree family members suggests this subset of PANS may share immune mechanisms with psoriasis and arthritis. Treatment strategies used in IBD and arthritis should be studied for potential application in PANS.