Neurobehavioral Evaluation Research Articles

Discovery of E0199: A novel compound targeting both peripheral NaV and KV7 channels to alleviate neuropathic pain

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both NaV1.7, NaV1.8, and NaV1.9 and KV7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited NaV1.7, NaV1.8, and NaV1.9 channels with a particularly low half maximal inhibitory concentration (IC50) for NaV1.9 by promoting sodium channel inactivation, and also effectively increased KV7.2/7.3, KV7.2, and KV7.5 channels, excluding KV7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Explaining recovery from coma with multimodal neuroimaging

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients’ neurological recovery after coma. 32 patients (18–76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient’s hospitalization were used to derive cortical glucose metabolism (18F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p < .001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = − 0.74, p < 0.001, 95% CI: − 0.46, − 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R2 = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R2 = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R2 = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury.

Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitorfor the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aβ-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future.

CYR61 is Involved in Neonatal Hypoxic-ischemic Brain Damage Via Modulating Astrocyte-mediated Neuroinflammation

The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in astrocytes has been found in the hypoxic-ischemic brain damage (HIBD) model. Cysteine rich angiogenic inducer 61 (CYR61) is secreted by reactive astrocytes. However, the effects of CYR61 on HIBD and its related mechanisms remain unclear. This study sought to explore the role of CYR61 in the activation of astrocytes and the NLRP3 inflammasome in neonatal HIBD. HIBD models were established in 7-day Sprague-Dawley rat pups. Neurobehavioral evaluation and 2,3,5-triphenyl-tetrazolium chloride staining were performed. In addition, rat primary astrocytes were used to establish the cell model of HIBD in vitro by oxygen-glucose deprivation/reperfusion (OGD/R). Then, CYR61-overexpression and sh-CYR61 viruses mediated by lentivirus were transduced into ODG/R-treated primary astrocytes. The expressions of related genes were evaluated using real-time quantitative PCR, western blot, immunofluorescence staining, and Enzyme-linked immunosorbent assay. The results showed that hypoxia–ischemia induced short-term neurological deficits, neuronal damage, and cerebral infarction in neonatal rats. In vivo, the expressions of CYR61, NLRP3, and glial fibrillary acidic protein (GFAP) were up-regulated in the HIBD model. In vitro, CYR61 exhibited high expression. CYR61 overexpression increased the expressions of GFAP and C3, whereas decreased S100A10 expression. CYR61 overexpression increased the expression of NLRP3, ASC, caspase-1 p20 and IL-1β. CYR61 overexpression activated NF-κB by promoting the phosphorylation of IκBα and p65. Thus, CYR61 is involved in neonatal HIBD progress, which may be related to the activation of astrocytes, the NLRP3 inflammasome, and the NF-κB signaling pathway.

Mechanism of Fat Mass and Obesity-Related Gene-Mediated Heme Oxygenase-1 m6A Modification in the Recovery of Neurological Function in Mice with Spinal Cord Injury.

This study examined the mechanism of fat mass and obesity-related gene (FTO)-mediated heme oxygenase-1 (HO-1) m6A modification facilitating neurological recovery in spinal cord injury (SCI) mice. FTO/HO-1 was identified as a key regulator of SCI as well as a potential target for treatment of SCI. An SCI mouse was treated with pcDNA3.1-FTO/pcDNA3.1-NC/Dac51. An oxygen/glucose deprivation (OGD) cell model simulated SCI, with cells treated with pcDNA3.1-FTO/si-HO-1/Dac51. Motor function and neurobehavioral evaluation were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and modified neurological severity score (mNSS). Spinal cord pathology and neuronal apoptosis were assessed. Further, FTO/HO-1 mRNA and protein levels, HO-1 mRNA stability, the interaction of YTHDF2 with HO-1 mRNA, neuronal viability/apoptosis, and HO-1 m6A modification were evaluated. Spinal cord injury mice exhibited reduced BBB, elevated mNSS scores, disorganized spinal cord cells, scattered nuclei, and severe nucleus pyknosis. pcDNA3.1-FTO elevated FTO mRNA, protein expression, and BBB score; reduced the mNSS score of SCI mice; decreased neuronal apoptosis; improvedthe cell arrangement; and improved nucleus pyknosis in spinal cord tissues. OGD decreased FTO expression. FTO upregulation ameliorated OGD-induced neuronal apoptosis. pcDNA3.1-FTO reduced HO-1 mRNA and protein and HO-1 m6A modification, while increasing HO-1 mRNA stability and FTO in OGD-treated cells. FTO upregulated HO-1 by modulating m6A modification. HO-1 downregulation attenuated the effect of FTO. pcDNA3.1-FTO/Dac51 increased the HO-1 m6A level in mouse spinal cord tissue homogenate, reduced BBB, boosted mNSS scores of SCI mice, aggravated nucleus pyknosis, and increased neuronal apoptosis in spinal cord tissues, confirming that FTO mediated HO-1 m6A modification facilitated neurological recovery in SCI mice. The fat mass and obesity-related gene modulates HO-1 mRNA stability by regulating m6A modification levels, thereby influencing HO-1 expression and promoting neurological recovery in SCI mice.

UPLC-MS based metabonomics revealed the protective effects of Buyang Huanwu decoction on ischemic stroke rats.

Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy. We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels. This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.

Neuroprotective Effect of Aurothioglucose-Loaded PLGA Nanoparticles in an Aluminum Chloride-Induced Rat Model of Alzheimer's Disease

Background: In Ayurvedic medicine, herbal, metallic, and herbometalic preparations gain recognition for treating physiological maladies. Aurothioglucose serves as a pharmaceutical intervention for the management of rheumatoid arthritis and can be potential as a potential pharmacological agent for mitigating neuronal toxicity. Objective: The current study was planned to explore the neuroprotective potential of aurothioglucose-loaded poly (lactic-co-glycolic acid) nanoparticles against aluminum chloride (AlCl3) induced Alzheimer's Disease. Method: In the in vivo study, AlCl3 (100 mg/kg, 21 days) was orally administered to rats, while, Aurothioglucose (ATG) and ATG NPs (Nanoparticles) (5, 10 mg/kg and 2.5 and 5 mg/kg, s.c.) were administered sub-cutaneous for a duration of 2 weeks. Following the treatment regimen, neurobehavioral evaluations were conducted utilizing the Open Field Test (OFT), Morris Water Maze (MWM), and Object Recognition Test (ORT). Subsequently, the rats were euthanized, and hippocampal tissue samples were procured for the assessment of biochemical and neuroinflammatory markers. Results: In the in-vivo experiment, the administration of both ATG and ATGNPs elicited a noteworthy reversal of cognitive impairments, biochemical perturbations, and neuroinflammatory markers induced by AlCl3. These observations suggest that ATG NPs demonstrate superior neuroprotective capabilities compared to ATG alone. Conclusion: The observed therapeutic outcomes imply that ATG and ATG NPs conferred amelioration against AlCl3-induced neurotoxicity in rats through mechanisms involving antioxidative and anti-inflammatory effects. Hence, ATG NPs could be a potential drug for correcting Alzheimer’s disease.

Electroacupuncture attenuates cerebral ischemia/reperfusion injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ.

Oxidative stress and inflammatory responses play essential roles in cerebral ischemia/reperfusion (I/R) injury. Electroacupuncture (EA) is widely used as a rehabilitation method for stroke in China; however, the underlying mechanism of action remains unclear. Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been reported to impact anti-inflammatory and anti-oxidative effects. This study investigated the role of PPAR-γ in EA-mediated effects and aimed to illuminate its possible mechanisms in cerebral I/R. In this study, male Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury were treated with EA at LI11 and ST36 for 30 min daily after MCAO/R for seven consecutive days. The neuroprotective effects of EA were measured by neurobehavioral evaluation, triphenyltetrazolium chloride staining, hematoxylin-eosin staining and transmission electron microscopy. Oxidative stress, inflammatory factors, neural apoptosis and microglial activation were examined by enzyme-linked immunosorbent assay, immunofluorescence and reverse transcriptase polymerase chain reaction. Western blotting was used to assess PPAR-γ-mediated signaling. We found that EA significantly alleviated cerebral I/R-induced infarct volume, decreased neurological scores and inhibited I/R-induced oxidative stress, inflammatory responses and microglial activation. EA also increased PPAR-γ protein expression. Furthermore, the protective effects of EA were reversed by injection of the PPAR-γ antagonist T0070907. EA attenuates cerebral I/R injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ.

Abstract WMP74: Inhibition of T Cell Receptor Activation Improves Neurological Outcomes After Intracerebral Hemorrhage

Purpose: We previously reported that activated T cells accumulate in the perihematomal regions after Intracerebral hemorrhage (ICH) and aggravate hemorrhagic brain injury. However, brain-infiltrating T cells precise activation mechanisms and resulting pathological impacts remain largely unexplored. This study aims to address these knowledge gaps. Methodology: ICH was induced via standard collagenase injection in male C57BL/6J mice (10 weeks old). Activation pathways of T cells were analyzed through single-cell RNA data (GSE230414). We assessed T cell receptor (TCR) activation, pro-inflammatory cytokines expression, and immune cell infiltration via flow cytometry and immunostaining at 1- and 3-days post-ICH. Neurobehavioral evaluations were conducted at 1-, 3-, 7-, and 14-days post-ICH. TCR activation was pharmacologically inhibited using the TCR-specific inhibitor AX-024, administered (10 mg/kg, i.p.) one hour after ICH. Results: Single-cell transcriptomic analysis revealed an upregulation of the TCR pathway in activated T cells following ICH in mice. Flow cytometry and immunostaining validated TCR activation markers (p-CD3, p-Zap70) in ICH mouse models. These findings suggest that TCR activation likely plays a central role in the activation of brain-infiltrating T cells. In the subsequent experiment, we explored the pathological implications of TCR activation on T cell activation, leukocyte brain infiltration, and neurological outcomes post-ICH. We found that administration of AX-024 substantially inhibited TCR activation (CD69 expression) and expression of pro-inflammatory cytokines (IL-17, IL-1β) in brain-infiltrating T cells at 1- and 3-days post-ICH. Notably, AX-024 administration also significantly decreased the infiltration of other leukocytes and remarkably enhanced long-term sensorimotor and cognitive function up to 14 days after ICH. Discussion: This study underscores TCR activation as a pivotal mechanism driving activation of brain-infiltrating T cells following ICH. Inhibiting TCR activation through AX-024 proves beneficial for improving neurological outcomes after ICH. However, further investigations are warranted to comprehensively elucidate the intricate underlying pathological mechanisms.

Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19.

The risk factors for post-COVID-19 cognitive impairment have been poorly described. This study aimed to identify the sociodemographic, clinical, and lifestyle characteristics that characterize a group of post-COVID-19 condition (PCC) participants with neuropsychological impairment. The study sample included 426 participants with PCC who underwent a neurobehavioral evaluation. We selected seven mental speed processing and executive function variables to obtain a data-driven partition. Clustering algorithms were applied, including K-means, bisecting K-means, and Gaussian mixture models. Different machine learning algorithms were then used to obtain a classifier able to separate the two clusters according to the demographic, clinical, emotional, and lifestyle variables, including logistic regression with least absolute shrinkage and selection operator (LASSO) (L1) and Ridge (L2) regularization, support vector machines (linear/quadratic/radial basis function kernels), and decision tree ensembles (random forest/gradient boosting trees). All clustering quality measures were in agreement in detecting only two clusters in the data based solely on cognitive performance. A model with four variables (cognitive reserve, depressive symptoms, obesity, and change in work situation) obtained with logistic regression with LASSO regularization was able to classify between good and poor cognitive performers with an accuracy and a weighted averaged precision of 72%, a recall of 73%, and an area under the curve of 0.72. PCC individuals with a lower cognitive reserve, more depressive symptoms, obesity, and a change in employment status were at greater risk for poor performance on tasks requiring mentalprocessing speedand executive function. Study registration: www.ClinicalTrials.gov , identifier NCT05307575.

Neurobehavioral evaluation of quail treated with omega-3 and chlorpyrifos

Neurobehavioral evaluation of quail treated with omega-3 and chlorpyrifos

Dynamic Regulation of brsk2 in the Social and Motor Development of Zebrafish: A Developmental Behavior Analysis.

Both social and motor development play an essential role in an individual's physical, psychological, and social well-being. It is essential to conduct a dynamic analysis at multiple time points during the developmental process as it helps us better understand and evaluate the trajectory and changes in individual development. Recently, some studies found that mutations in the BRSK2 gene may contribute to motor impairments, delays in achieving motor milestones, and deficits in social behavior and communication skills in patients. However, little is known about the dynamic analysis of social and motor development at multiple time points during the development of the brsk2 gene. We generated a novel brsk2-deficient (brsk2ab-/-) zebrafish model through CRISPR/Cas9 editing and conducted comprehensive morphological and neurobehavioral evaluations, including that of locomotor behaviors, social behaviors, and anxiety behaviors from the larval to adult stages of development. Compared to wild-type zebrafish, brsk2ab-/- zebrafish exhibited a catch-up growth pattern of body length and gradually improved locomotor activities during the developmental process. In contrast, multimodal behavior tests showed that the brsk2ab-/- zebrafish displayed escalating social deficiency and anxiety-like behaviors over time. We reported for the first time that the brsk2 gene had dynamic regulatory effects on motor and social development. It helps us understand developmental trends, capture changes, facilitate early interventions, and provide personalized support and development opportunities for individuals.

Acute and Chronic Study of PTZ –Induced Seizure Effects on Visuo-Spatial Functions in Wistar Rats

Epilepsy is one of the chronic neurological conditions affecting people of all ages globally. Educational progress have been affected negatively by some abnormalities associated with epilepsy. This study employed neurobehavioural analysis of pentylenetetrazole (PTZ) induced seizure on some visual spatial functions in Wistar rats. The study was done in two phases: acute (14days) and chronic (28days). A total of twenty adult Wistar rats weighing between 90-120g were used. The rats were divided into four (4) groups (1-4, n=5). PTZ was administered intraperitoneally to the PTZ treated groups one (1) week before the neurobehavioral experiments commenced. Group 1 (control) received distilled water, group 2, 3and 4 were administered with doses of PTZ (25mg/kg, 30mg/kg and 35mg/kg) respectively at alternate days (48 hourly) until kindling was achieved. The study evaluated neurobehavioural parameters using Barnes maze (BM), navigational box test (NBT). The results from neurobehavioural evaluations on effects of the chemo-convulsant seizures on visual spatial functions, suggests that severity of seizures caused a deficit in learning and visual spatial memory which was worsened by chronicity. In conclusion, PTZ-induced seizure negatively interferes with visual spatial functions.

Neurobehavioral Evaluation Of Ethanolic extracts from Newbouldia Laevis leaf in 6-hydroxyldopamine- lesioned rat model of Parkinson’s disease treated with L-DOPA

Neurobehavioral Evaluation Of Ethanolic extracts from Newbouldia Laevis leaf in 6-hydroxyldopamine- lesioned rat model of Parkinson’s disease treated with L-DOPA

Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach

ObjectiveThe present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. MethodsTwenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. ResultsIntragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. ConclusionThe present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Prevalence of Early Feeding Alterations Among Preterm Infants and Their Relationship to Early Neurobehavior.

Feeding difficulties are common among preterm infants during neonatal intensive care unit (NICU) hospitalization. Although most preterm infants achieve full oral feeding by term-equivalent age, whether feeding difficulties persist despite the infant taking full volume and whether these difficulties may relate to other neurobehavioral challenges remain unclear. To identify the prevalence of feeding problems among preterm infants and the relationships between infant feeding behaviors and neurobehavior at term-equivalent age. Cohort study. Level 4 NICU with 85 beds. Thirty-nine very preterm infants born ≤32 wk gestation (range = 22-32 wk). Exclusion criteria were congenital anomalies, >32 wk gestation at birth, and lack of feeding or neurobehavioral assessment at term-equivalent age. Standardized feeding assessments using the Neonatal Eating Outcome Assessment and standardized neurobehavioral evaluation using the NICU Network Neurobehavioral Scale. Thirty-nine infants (21 female) were included in the final analysis. The mean Neonatal Eating Outcome Assessment score was 66.6 (SD = 13.3). At term-equivalent age, 10 infants (26%) demonstrated feeding challenges, 21 (54%) demonstrated questionable feeding issues, and 8 (21%) demonstrated normal feeding performance. Lower Neonatal Eating Outcome Assessment scores (poorer feeding performance) at term-equivalent age were associated with more suboptimal reflexes (p = .04) and hypotonia (p < .01). Feeding challenges and questionable feeding performance were prevalent among preterm infants at term-equivalent age and appeared in conjunction with suboptimal reflexes and hypotonia. Understanding this finding enables therapists to take a holistic approach to addressing feeding difficulties. What This Article Adds: Elucidating the relationships between feeding performance and neurobehavior during the neonatal period allows for a better understanding of potential contributors to early feeding challenges and identifies targets for intervention.

The somatosensory and visual systems adaptation times have a strong positive correlation.

CONNIE BURRIS, MARIA MARTINEZ, RAE MOORE, SARAH ZAMZOW, NATALIA OMELCHENKO-COMER, STEM and Business Division, WVNCC, Wheeling, WV, 26003. The somatosensory and visual systems adaptation times have a strong positive correlation. &#x0D; Multiple studies demonstrated that all sensory systems adapt their sensitivity levels to improve their responsiveness to changes in corresponding stimulation and to accelerate following CNS processing. The study aimed to determine if the time of adaptation observed for the somatosensory system correlates with the adaptation time observed for the visual system. The data collection was performed on 2 male and 7 female healthy volunteers (the average age of those was 22.2+/-4.60, 8 right-handed and 1 left-handed) in a seated position. The adaptation time for the somatosensory system was estimated by recording the time of the perception loss after placing a 1 penny coin onto the dorsal hand surface. To evaluate the adaptation time for the visual system the subject was asked to stare at a small pastel color abstract image. The time of the perceived loss for the component of this image was recorded. The average adaptation time for somatosensory perception was 22.0+/-16.15 seconds ranging from 4 to 42 seconds. The average adaptation time for visual perception was 30.7+/-16.04 seconds ranging from 12 to 51 seconds. There was a statistically significant difference between the adaptation time for these modalities of the sensations as determined by paired T-test (t (8) = 3.1, p = .01). However, the correlation analysis demonstrated a strong positive correlation between values (r (8) = 0.86, p = .003). Our data indicate that the times of somatosensory and visual adaptation are strongly correlated. The finding of this study can be used for the development and improvement of neurobehavioral evaluation tests.

Development of informant-report neurobehavioral survey scales for PTEN hamartoma tumor syndrome and related neurodevelopmental genetic syndromes.

There are few well-validated measures that are appropriate for assessing the full range of neurobehavioral presentations in PTEN hamartoma tumor syndrome (PHTS) and other neurodevelopmental genetic syndromes (NDGS). As potential therapeutics are developed, having reliable, valid, free, and easily accessible measures to track a range of neurobehavioral domains will be crucial for future clinical trials. This study focused on the development and initial psychometric evaluation of a set of freely available informant-report survey scales for PHTS-the Neurobehavioral Evaluation Tool (NET). Concept elicitation, quantitative ratings, and cognitive interviewing processes were conducted with stakeholders and clinician-scientist experts, used to identify the most important neurobehavioral domains for this population, and to ensure items were appropriate for the full range of individuals with PHTS. Results of this process identified a PHTS neurobehavioral impact model with 11 domains. The final NET scales assessing these domains were administered to a sample of 384 participants (median completion time = 20.6 min), including 32 people with PHTS, 141 with other NDGS, 47 with idiopathic neurodevelopmental disorder (NDD), and 164 neurotypical controls. Initial psychometric results for the total scores of each scale indicated very good model (ω = 0.83-0.99) and internal consistency reliability (α = 0.82-0.98) as well as excellent test-retest reproducibility at 1-month follow-up (r = 0.78-0.98) and stability at 4-month follow-up (r = 0.76-0.96). Conditional reliability estimates indicated very strong measurement precision in key score ranges for assessing PHTS and other people with NDGS and/or idiopathic NDD. Comparisons across domains between PHTS and the other groups revealed specific patterns of symptoms and functioning, including lower levels of challenging behavior and more developed daily living and executive functioning skills relative to other NDGS. The NET appears to be a reliable and potentially useful tool for clinical characterization and monitoring of neurobehavioral symptoms in PHTS and may also have utility in the assessment of other NDGS and idiopathic NDD. Additional validation work, including convergent and discriminant validity analyses, are needed to replicate and extend these observations.

Functional networks in prolonged disorders of consciousness.

Prolonged disorders of consciousness (DoC) are characterized by extended disruptions of brain activities that sustain wakefulness and awareness and are caused by various etiologies. During the past decades, neuroimaging has been a practical method of investigation in basic and clinical research to identify how brain properties interact in different levels of consciousness. Resting-state functional connectivity within and between canonical cortical networks correlates with consciousness by a calculation of the associated temporal blood oxygen level-dependent (BOLD) signal process during functional MRI (fMRI) and reveals the brain function of patients with prolonged DoC. There are certain brain networks including the default mode, dorsal attention, executive control, salience, auditory, visual, and sensorimotor networks that have been reported to be altered in low-level states of consciousness under either pathological or physiological states. Analysis of brain network connections based on functional imaging contributes to more accurate judgments of consciousness level and prognosis at the brain level. In this review, neurobehavioral evaluation of prolonged DoC and the functional connectivity within brain networks based on resting-state fMRI were reviewed to provide reference values for clinical diagnosis and prognostic evaluation.

Regional Vulnerability of the Corpus Callosum in the Context of Cardiovascular Risk.

Many factors outside of cardiovascular health can impact the structure of white matter. Identification of reliable and clinically meaningful biomarkers of the neural effects of systemic and cardiovascular health are needed to refine etiologic predictions. We examined whether the corpus callosum demonstrates regional vulnerability to systemic cardiovascular risk factors. Three hundred and ninety-four older adults without dementia completed brain MRI, neurobehavioral evaluations, and blood draws. A subset (n = 126, n = 128) of individuals had blood plasma analyzed for inflammatory markers of interest (IL-6 and TNF-alpha). Considering diffusion tensor imaging (DTI) is a particularly reliable measure of white matter integrity, we utilized DTI to examine fractional anisotropy (FA) of anterior and posterior regions of the corpus callosum. Using multiple linear regression models, we simultaneously examined FA of the genu and the splenium to compare their associations with systemic and cardiovascular risk factors. Lower FA of the genu but not splenium was associated with greater systemic and cardiovascular risk, including higher systolic blood pressure (β = -0.17, p = .020), hemoglobin A1C (β = -0.21, p = .016) and IL-6 (β = -0.34, p = .005). FA of the genu was uniquely associated with cognitive processing speed (β = 0.20, p = .0015) and executive functioning (β = 0.15, p = .012), but not memory performances (β = 0.05, p = .357). Our results demonstrated differential vulnerability of the corpus callosum, such that frontal regions showed stronger, independent associations with biomarkers of systemic and cardiovascular health in comparison to posterior regions. Posterior white matter integrity may not reflect cardiovascular health. Clinically, these findings support the utility of examining the anterior corpus callosum as an indicator of cerebrovascular health.