Biology subjects

Anderson, A. E.

Publications and source records attributed to Anderson, A. E..

12 recordsLinked to original sources

bioRxiv2026

Perspectives in conducting task-based research in pediatric surgical epilepsy patients

ObjectivePediatric epilepsy patients undergoing stereo-electroencephalography (sEEG) for ictal onset evaluation provide a rare window to study the developing brain. While methodological frameworks for task-based sEEG research are well-established in adults, pediatric-specific guidance remains underdeveloped. Furthermore, many pediatric epilepsy patients have comorbidities that might typically exclude them from participating in research. We examine factors that influence research participation and discuss considerations for conducting sEEG research in children. MethodsHere, we present a retrospective analysis of task-based research participation patterns from an NIH-funded study of speech and language representations (1R01DC018579) in 66 patients (ages 4-24) undergoing sEEG monitoring at Texas Childrens Hospital to determine whether specific comorbidities influenced research participation. ResultsEighty-nine percent (n=66) of patients approached for consent agreed to participate in the study. Despite high rates of comorbidities including neurocognitive disorder (66.67%), language delay (31.75%), global developmental delay (23.81%), mood disorders (33.33%), ADHD (46.03%), autism spectrum disorder (14.29%) or other cognitive/intellectual disabilities (36.51%), all participants engaged in at least one task. While the majority of these diagnoses did not appear to influence subject participation, global developmental delay was associated with a significant reduction in time spent on active tasks. DiscussionDespite high prevalence of neuropsychological comorbidities among participants, our evidence suggests that these participants contribute meaningfully to studies investigating important developmental questions. We suggest strategies for tailoring task-based research to accommodate the unique needs of individuals in this population. Such practices are important for ensuring that research studies reflect the true diversity of the population.

neuroscience↗

bioRxiv2026

Human auditory cortex preferentially tracks speech over music without explicit attention

Our brains constantly filter incoming sounds to understand our environment. While extensively studied in adults, how this ability develops across childhood remains unclear. We recorded intracranial brain activity from 54 participants aged 4-21 while they watched movie clips containing simultaneous speech and music. We used deep neural networks to separate the mixed audio into isolated speech and music streams, then built encoding models to determine which stream best predicted neural responses in the auditory cortex. Although participants heard only the original mixture with no instruction to attend to either stream, higher-order auditory regions including the superior temporal gyrus (STG), superior temporal sulcus (STS) and middle temporal gyrus (MTG), responded preferentially to speech. This speech-bias strengthened with age in STG, suggesting that this region progressively sharpens its representation of socially relevant sound across development. These findings indicate that speech prioritization in the developing brain emerges automatically, without directed attention.

neuroscience↗

bioRxiv2026

Elevated Delta Power in a Maternal UBE3A-Deletion Pig Model of Angelman Syndrome

Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternally inherited UBE3A allele and is characterized by severe cognitive, motor, and communication impairments. Increased delta (1- 4 Hz) activity on electroencephalogram (EEG) assessed by visual inspection and by spectral power analysis is a robust feature of the disorder in humans and rodent models and is used as a biomarker of Angelman syndrome. This aspect of the phenotype has not been evaluated in the recently developed pig model of Angelman syndrome. Here, we analyzed scalp EEG recordings from freely moving pigs carrying a maternal UBE3A deletion (UBE3A-/+) across three age groups to determine whether they recapitulate the delta power abnormalities characteristic of the disorder. UBE3A-/+ pigs exhibited elevated delta power during both wakefulness and sleep compared with wild-type littermates, with the largest differences observed during the awake state. The typical increase in delta power that accompanies the transition from wakefulness to sleep was also reduced in UBE3A-/+ pigs. These effects were observed across study groups, demonstrating that the maternal UBE3A-deletion pig model reproduces the elevated delta power EEG phenotype of Angelman syndrome. Our results establish noninvasive scalp EEG as a translationally relevant tool for assessing neural dysfunction in this large-animal model and provide a framework for preclinical therapeutic testing. This work strengthens the utility of the pig model for mechanistic studies and therapeutic development in Angelman syndrome.

neuroscience↗

bioRxiv2024

IGF-1 IMPACTS NEOCORTICAL INTERNEURON CONNECTIVITY IN EPILEPTIC SPASM GENERATION AND RESOLUTION

Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. IGF-1 expression was also reduced, but surprisingly this loss was confined to interneurons. Interneuron connectivity was reduced in tandem with IGF-1 deficiencies. Similar changes were observed in surgically resected neocortex from infantile epileptic spasms syndrome (IESS) patients. To evaluate the impact of IGF-1 deficiencies on interneuron development, IGF-1R levels were reduced in the neocortex of neonatal conditional IGF-1R knock out mice by viral injections. Four weeks later, this experimental maneuver resulted in similar reductions in interneuron connectivity. Treatment with the IGF-1 derived tripeptide, (1-3)IGF-1, abolished epileptic spasms in most animals, rescued interneuron connectivity, and restored neocortical levels of IGF-1. Our results implicate interneuron IGF-1 deficiencies, possibly impaired autocrine IGF-1 signaling and a resultant interneuron dysmaturation in epileptic spasm generation. By restoring IGF-1 levels, (1-3)IGF-1 likely suppresses spasms by rescuing interneuron connectivity. Results point to (1-3)IGF-1 and its analogues as potential novel disease-modifying therapies for this neurodevelopmental disorder.

neuroscience↗

bioRxiv2024

Shox2 is necessary for normal thalamic spindle function

The cellular identity of thalamocortical neurons (TCNs), namely their firing properties, dictates brain-wide activity patterns, such as sleep spindles. Transcription factors are critical to the determination of cellular identity. Previously, we discovered that a subset of TCNs express the transcription factor, Shox2, and, in a global Shox2 KO, established that TCNs within the anterior nucleus of the thalamus rely on the expression of Shox2 to regulate key ion channels that are necessary to maintain their firing properties. From this, we hypothesized that Shox2 expression, through the regulation of firing properties of TCNs, is critical for the thalamocortical circuit to generate spindle oscillations. We exploited the somatosensory thalamocortical circuit to investigate this by creating a primary somatosensory thalamus (VB) Shox2 knockdown mouse model. We delivered Cre into the VB of P21 Shox2fl/fl mice using viral infection and compared in vitro, patch-clamp recordings from Shox2+ and Shox2 knockdown TCNs, finding that Shox2 expression is indeed critical to maintain burst and tonic firing properties of VB TCNs. Since Shox2 is important developmentally and firing from TCNs to cortex during development structures the circuit, we performed ultrasound-guided P3 injections at P3 to generate an early-stage, Shox2 VB knockdown, but found no changes in the layer four, barrel map (VB cortical target). Despite this, Shox2 knockdown mice exhibit reduced sleep-spindle EEG density. Further, key behaviors associated with spindles and proper VB thalamic function--memory consolidation and somatosensory perception--are significantly impaired. These results indicate that the impact on spindle function is likely due to cell autonomous changes to TCNs rather than circuit changes, confirming our hypothesis that Shox2 is necessary for normal thalamic spindle function and implicating a potential role for Shox2 in autism and schizophrenia pathologies.

neuroscience↗

bioRxiv2024

Processing of auditory feedback in perisylvian and insular cortex

When we speak, we not only make movements with our mouth, lips, and tongue, but we also hear the sound of our own voice. Thus, speech production in the brain involves not only controlling the movements we make, but also auditory and sensory feedback. Auditory responses are typically suppressed during speech production compared to perception, but how this manifests across space and time is unclear. Here we recorded intracranial EEG in seventeen pediatric, adolescent, and adult patients with medication-resistant epilepsy who performed a reading/listening task to investigate how other auditory responses are modulated during speech production. We identified onset and sustained responses to speech in bilateral auditory cortex, with a selective suppression of onset responses during speech production. Onset responses provide a temporal landmark during speech perception that is redundant with forward prediction during speech production. Phonological feature tuning in these "onset suppression" electrodes remained stable between perception and production. Notably, the posterior insula responded at sentence onset for both perception and production, suggesting a role in multisensory integration during feedback control.

neuroscience↗

bioRxiv2023

One size does not fit all: Family specific differences in seasonal patterns of abundance and behavior in butterfly communities

Animal communities can undergo seasonal shifts in assemblage, responding to changes in their environment. Animal behavior can also shift due to seasonal environmental variation, with the potential to shape ecosystems. However, it is unclear if similar environmental factors and time scales affect both abundance and behavior. We examined how butterfly abundance and behavior change seasonally in temperate prairies and a butterfly garden, and if the factors driving variation differ between taxonomic families. We conducted monthly abundance surveys year-round and biweekly abundance and behavior surveys during the summer and fall, in 2017-2021 and 2018-2020 respectively. We also determined how ambient light, temperature, precipitation, and time of year interact to affect butterfly abundance and behavior. We found increased temperature and light levels correlate with increases in general butterfly abundance. Unlike the greater community, Lycaenidae abundance decreased as weekly precipitation increased, and Papilionidae abundance did not respond to changes in environmental factors. Only Nymphalidae changed behavior in response to environmental factors, increasing thermoregulatory behaviors as temperature and light levels decreased. These results indicate that lineages may differ in their sensitivity to environmental factors, which could result in disproportionate changes in their abundances in response to future climate change and anthropogenic-driven disturbance.

ecology↗

bioRxiv2022

Helminth egg derivatives as pro-regenerative immunotherapies

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4 expressing T helper cells, eosinophils, and regulatory T cells, and decreased expression of IL-17A in gamma delta ({gamma}{delta}) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a new regenerative immunotherapy approach using natural helminth-derivatives. One-Sentence SummaryHelminth-derived soluble egg antigen regenerative immunotherapies promote tissue repair in multiple injury models.

bioengineering↗

bioRxiv2021

Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome

BackgroundAngelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. MethodsWe used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. ResultsAcute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability, however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LimitationsThe generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. ConclusionsDespite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mice or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.

pharmacology and toxicology↗

bioRxiv2021

Genetic expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy

Hyperactivation of mTOR signaling during fetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development (FMCD) and intractable epilepsy. Recent evidence suggests increased cap-dependent translation downstream of mTOR contributes to FMCD formation and seizures. However, whether reducing overactive translation once the developmental pathologies are established reverses neuronal abnormalities and seizures is unknown. Here, we found that the translational repressor 4E-BP1, which is inactivated by mTOR-mediated phosphorylation, is hyperphosphorylated in patient FMCD tissue and in a mouse model of FMCD. Expressing constitutive active 4E-BP1 to repress aberrant translation in juvenile mice with FMCD reduced neuronal cytomegaly and corrected several electrophysiological alterations, including depolarized resting membrane potential, irregular firing pattern, and aberrant HCN4 channel expression. This was accompanied by improved cortical spectral activity and decreased seizures. Although mTOR controls multiple pathways, our study shows that targeting 4E-BP1-mediated translation alone is sufficient to alleviate neuronal dysfunction and ongoing epilepsy.

neuroscience↗

bioRxiv2019

Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 CNV Mediated Risk for Neuropsychiatric Disorders

Background22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear. MethodsUsing a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder. ResultsPolygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways. SEPT5, PI4KA, and SNAP29 genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, and DGCR8 and HIRA are candidate drivers of disease-relevant alterations in gene regulation. ConclusionsThe current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.

systems biology↗

bioRxiv2018

A novel model for the induction of postnatal murine hip deformity

Acetabular dysplasia is a recognized cause of hip osteoarthritis (OA). A paucity of animal models exists to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent arthritic cascade. Utilizing a novel murine model, this study investigated the role of surgically-induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. Specifically, C57BL6 mice were used to develop titrated levels of hip instability (mild, moderate, severe, and femoral head removal) at 3-weeks of age, a critical time for hip maturation. Joint shape, acetabular coverage, histomorphology, immunohistochemistry, and statistical shape modeling were used to assess overall quality of joint health and three-dimensional hip shape following 8 weeks of titrated destabilization. This titrated approach included mild, moderate, severe, and complete instability via surgical destabilization of the murine hip. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femoral head without dislocation, whereas severe instability led to complete dislocation and formation of pseudoacetabula. Mild instability did not result in statistically significant morphological changes to the hip. Complete destabilization via femoral head removal led to reduced joint space volume and reduced bone volume ratio in the remnant proximal femur. Collectively, these results support the notion that hip instability, driven by loss of function, leads to morphometric changes in the maturing mouse hip. This model could be useful for future studies investigating the mechanical and cellular adaptations to hip instability during maturation.

pathology↗