scholarly journals Perinatal Penicillin Exposure Affects Cortical Development and Sensory Processing

2021 ◽  
Vol 14 ◽  
Author(s):  
James Perna ◽  
Ju Lu ◽  
Brian Mullen ◽  
Taohui Liu ◽  
Michelle Tjia ◽  
...  

The prevalent use of antibiotics in pregnant women and neonates raises concerns about long-term risks for children’s health, but their effects on the central nervous system is not well understood. We studied the effects of perinatal penicillin exposure (PPE) on brain structure and function in mice with a therapeutically relevant regimen. We used a battery of behavioral tests to evaluate anxiety, working memory, and sensory processing, and immunohistochemistry to quantify changes in parvalbumin-expressing inhibitory interneurons (PV+ INs), perineuronal nets (PNNs), as well as microglia density and morphology. In addition, we performed mesoscale calcium imaging to study neural activity and functional connectivity across cortical regions, and two-photon imaging to monitor dendritic spine and microglial dynamics. We found that adolescent PPE mice have abnormal sensory processing, including impaired texture discrimination and altered prepulse inhibition. Such behavioral changes are associated with increased spontaneous neural activities in various cortical regions, and delayed maturation of PV+ INs in the somatosensory cortex. Furthermore, adolescent PPE mice have elevated elimination of dendritic spines on the apical dendrites of layer 5 pyramidal neurons, as well as increased ramifications and spatial coverage of cortical microglia. Finally, while synaptic defects are transient during adolescence, behavioral abnormalities persist into adulthood. Our study demonstrates that early-life exposure to antibiotics affects cortical development, leaving a lasting effect on brain functions.

Author(s):  
Eamonn Arble ◽  
Steven W. Steinert ◽  
Ana M. Daugherty

Abstract. The Rorschach Inkblot test has been adopted and adapted by many researchers to assess and predict different aspects of human experience and cognitive performance. The present review examines research that incorporates the Rorschach to evaluate neural and cognitive aging as well as decline in age-related disease. Specifically, differences in amygdala and cortical regions, as well as mirror neuron and asymmetrical hemisphere activity that correlate with specific responses to Rorschach stimuli are discussed in the context of typical changes in brain structure and function in the course of aging. In addition, the present review provides a proposed framework for expanding the use of the Rorschach to evaluate other domains of neural and cognitive function. The authors conclude that, despite a need for increased research, the Rorschach is a viable measure to evaluate certain aspects of cognitive function and decline throughout the lifespan.


2018 ◽  
Author(s):  
Leila Ghanbari ◽  
Russell E. Carter ◽  
Matthew L. Rynes ◽  
Judith Dominguez ◽  
Gang Chen ◽  
...  

ABSTRACTNeural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating cognition, perception and sensorimotor behaviors. Enormous progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. To fill this need, we have engineered “See-Shells” – digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>200 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm through the See-Shells. See-Shells implanted on transgenic mice expressing genetically encoded calcium (Ca2+) indicators allow tracking of neural activities from multiple, non-contiguous regions spread across millimeters of the cortex. Further, neural probes can access the brain through perforated See-Shells, either for perturbing or recording neural activity from localized brain regions simultaneously with whole cortex imaging. As See-Shells can be constructed using readily available desktop fabrication tools and modified to fit a range of skull geometries, they provide a powerful tool for investigating brain structure and function.


2018 ◽  
Author(s):  
Bonnie Alexander ◽  
Wai Yen Loh ◽  
Lillian G. Matthews ◽  
Andrea L. Murray ◽  
Chris Adamson ◽  
...  

AbstractOur recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: a) compatibility with this adult cortical atlas, b) greater labelling accuracy due to clearer landmarks, and c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for ten healthy neonates (postmenstrual age at MRI 40-43 weeks, 4 female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and ‘Banks STS’, and modification of boundaries of many other regions. Changes to subcortical regions included the addition of ‘ventral diencephalon’, and deletion of ‘subcortical matter’ labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labelled cortical data and FreeSurfer-labelled subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 372-373
Author(s):  
Alexander Maher ◽  
Kenneth Rostowsky ◽  
Nikhil Chaudhari ◽  
Nahian Chowdhury ◽  
Elliot Jacobs ◽  
...  

Abstract Traumatic brain injuries (TBIs) are frequently followed by persistent brain alterations and by cognitive sequalae, especially in older adults. Although mild TBI (mTBI) is a risk factor for Alzheimer’s disease (AD), the extent to which the two conditions are related remains largely unexplored. Using structural, functional and diffusion magnetic resonance imaging (MRI), we have identified AD-like post-traumatic neurodegeneration patterns that accurately prognosticate cognitive decline after geriatric mTBI. Our results indicate that these features involve cortical regions and circuitry mediating memory and executive function, and that AD neurodegeneration has key structural and functional similarities to post-traumatic neurodegradation. Using machine learning of such similarities, we have accurately forecast the severity of chronic cognitive deficits after geriatric mTBI based on acute neuroimaging measures. Our findings demonstrate that AD-like alterations in brain structure and function observed early after injury can predict post-traumatic mild cognitive impairment, which is itself strongly associated with AD risk.


2018 ◽  
Author(s):  
Karen Runge ◽  
Rémi Mathieu ◽  
Stéphane Bugeon ◽  
Sahra Lafi ◽  
Corinne Beurrier ◽  
...  

AbstractWe identified seven families associating NEUROD2 pathogenic mutations with ASD and intellectual disability. To get insight into the pathophysiological mechanisms, we analyzed cortical development in Neurod2 KO mice. Cortical projection neurons (CPNs) over-migrated during embryogenesis, inducing abnormal thickness and laminar positioning of cortical layers. At juvenile ages, dendritic spine turnover and intrinsic excitability were increased in L5 CPNs. Differentially expressed genes in Neurod2 KO mice were enriched for voltage-gated ion channels, and the human orthologs of these genes were strongly associated with ASD. Furthermore, adult Neurod2 KO mice exhibited core ASD-like behavioral abnormalities. Finally, by generating Neurod2 conditional mutant mice we demonstrate that forebrain excitatory neuron-specific Neurod2 deletion recapitulates cellular and behavioral ASD phenotypes found in full KO mice. Our findings demonstrate crucial roles for Neurod2 in cortical development and function, whose alterations likely account for ASD and related symptoms in the newly defined NEUROD2 mutation syndrome.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1074
Author(s):  
Clemens von Schacky

Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood. Blood levels of EPA and DHA reflect dietary intake and other variables and are preferably assessed as percentage in erythrocytes with a well-documented and standardized analytical method (HS-Omega-3 Index®). Every human being has an Omega-3 Index between 2 and 20%, with an optimum of 8–11%. Compared to an optimal Omega-3 Index, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies. Most intervention trials, and their meta-analyses considered EPA and DHA as drugs with good bioavailability, a design tending to produce meaningful results in populations characterized by low baseline blood levels (e.g., in major depression), but otherwise responsible for many neutral results and substantial confusion. When trial results were evaluated using blood levels of EPA and DHA measured, effects were larger than comparing EPA and DHA to placebo groups, and paralleled epidemiologic findings. This indicates future trial design, and suggests a targeted use EPA and DHA, based on the Omega-3 Index.


2019 ◽  
Author(s):  
Elisabeth A. Wilde ◽  
Emily L. Dennis ◽  
David F Tate

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium brings together researchers from around the world to try to identify the genetic underpinnings of brain structure and function, along with robust, generalizable effects of neurological and psychiatric disorders. The recently-formed ENIGMA Brain Injury working group includes 8 subgroups, based largely on injury mechanism and patient population. This introduction to the special issue summarizes the history, organization, and objectives of ENIGMA Brain Injury, and includes a discussion of strategies, challenges, opportunities and goals common across 6 of the subgroups under the umbrella of ENIGMA Brain Injury. The following articles in this special issue, including 6 articles from different subgroups, will detail the challenges and opportunities specific to each subgroup.


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