Central Alpha Research Articles

Modulation of Brain Activities in Healthy Individuals by Acupuncture at Quchi (LI11).

This research investigated the modulation of acupuncture at Quchi (LI11) on the brain activities in healthy individuals. Sub-bands power and EEG microstate analysis were carried out at pre-acupuncture, acupuncture, needle retaining and post-acupuncture periods in both the acupuncture group (n = 16) and control group (n = 18). Four microstate classes (A-D) were derived from the clustering procedure. Regression analysis was conducted, together with a two-way repeated measures ANOVA, which was then followed by Bonferroni correction. In the acupuncture group, we found the beta power during the acupuncture periods was significantly reduced. The channel-by-channel analysis revealed that acupuncture at LI11 mainly altered the power of delta, theta, and alpha waves in specific brain regions. The delta power increased predominantly in parietal, occipital, and central lobes, while theta and alpha power decreased predominantly in temporal, frontal, parietal, and occipital lobes. During the acupuncture period, participants in the acupuncture group showed a significant increase in both duration and contribution of microstate A, as well as the bidirectional transition probabilities A and B/D. Microstate analysis showed that acupuncture at LI11 significantly enhances the activity of microstate A and potentially strengthens the functional connectivity between the auditory network and either the visual network or the dorsal attention network. These correlational results indicate that acupuncture at LI11 mainly affects activities of the frontal, temporal, parietal, and occipital lobes. These findings highlight the potential of microstate as neuroimaging evidence and a specific index for elucidating the neuromodulatory effects of acupuncture at LI11.

EEG-based Signatures of Schizophrenia, Depression, and Aberrant Aging: A Supervised Machine Learning Investigation.

Electroencephalography (EEG) is a noninvasive, cost-effective, and robust tool, which directly measures in vivo neuronal mass activity with high temporal resolution. Combined with state-of-the-art machine learning (ML) techniques, EEG recordings could potentially yield in silico biomarkers of severe mental disorders. Pathological and physiological aging processes influence the electrophysiological signatures of schizophrenia (SCZ) and major depressive disorder (MDD). From a single-center cohort (N = 735, 51.6% male) comprising healthy control individuals (HC, N = 245) and inpatients suffering from SCZ (N = 250) or MDD (N = 240), we acquired resting-state 19 channel-EEG recordings. Using repeated nested cross-validation, support vector machine models were trained to (1) classify patients with SCZ or MDD and HC individuals and (2) predict age in HC individuals. The age model was applied to patient groups to calculate Electrophysiological Age Gap Estimation (EphysAGE) as the difference between predicted and chronological age. The links between EphysAGE, diagnosis, and medication were then further explored. The classification models robustly discriminated SCZ from HC (balanced accuracy, BAC = 72.7%, P < .001), MDD from HC (BAC = 67.0%, P < .001), and SCZ from MDD individuals (BAC = 63.2%, P < .001). Notably, central alpha (8-11 Hz) power decrease was the most consistently predictive feature for SCZ and MDD. Higher EphysAGE was associated with an increased likelihood of being misclassified as SCZ in HC and MDD (ρHC = 0.23, P < .001; ρMDD = 0.17, P = .01). ML models can extract electrophysiological signatures of MDD and SCZ for potential clinical use. However, the impact of aging processes on diagnostic separability calls for timely application of such models, possibly in early recognition settings.

Combined assessment of acetabular coverage and femoral head-neck shapes predicts osteoarthritis progression after periacetabular osteotomy.

Postoperative osteoarthritis (OA) progression is a major determinant of failure after curved periacetabular osteotomy (CPO). A large postoperative combination angle, i.e., the combination of computed tomography-based anterior center edge and alpha angles, is associated with femoroacetabular impingement after CPO, but its association with postoperative OA progression is unclear. We aimed to identify the anatomical parameters that can lead to OA progression after CPO and the impact of the combination angle on the same. We included 90 hips that were subjected to CPO at our center between March 2013 and March 2018. Seventeen hips showed OA progression with an increase in the Tönnis classification after surgery; 73 hips showed no progression. Radiographic anatomical parameters, including the lateral and anterior center edge angles, femoral and acetabular anteversion, and combination angle, and clinical outcomes, including modified Harris Hip Scores (mHHSs), postoperative anterior impingement, and range of motion, were compared between the two groups. Statistical significance was set at P < 0.05. Postoperative OA progression was significantly affected by preoperative OA evidence (P = 0.017), acetabular anteversion < 5.0° (P = 0.003), and a combination angle > 107.0° (P = 0.025). Patients with radiographic OA progression were associated with poor mHHSs (P = 0.017) and high frequencies of anterior impingement with a limited hip flexion and internal rotation angle. OA progression after CPO may be associated with preoperative evidence of OA and postoperative acetabular retroversion as well as a large combination angle. Surgeons should focus on the potential effects of preoperative OA grades, postoperative reduction in acetabular anteversion, and postoperative combination angle.

Right Central CNZ Property Skewed by Ring Endomorphisms

The concept of the reversible ring property concerning nilpotent elements was introduced by A.M. Abdul-Jabbar and C. A. Ahmed, who introduced the concept of commutativity of nilpotent elements at zero, termed as a CNZ ring, as an extension of reversible rings. In this paper, we extend the CNZ property through the influence of a central ring endomorphism alpha , introducing a new type of ring called a right alpha -skew central CNZ ring. This concept not only expands upon CNZ rings but also serves as a generalization of right alpha -skew central reversible rings. We explore various properties of these rings and delve into extensions of right alpha -skew central CNZ rings, along with examining several established results, which emerge as corollaries of our findings.

TRUE REFRACTORY HYPERTENSION IN 2023- LESSONS LEARNED FROM A NATIONAL REGISTRY OF 1.82 MILLION ADULTS

Objective: Refractory hypertension (refHTN) is defined as blood pressure that remains uncontrolled on maximal therapy, which is defined as the use of 5 or more antihypertensive agents of different drug classes. We aimed to define the prevalence of apparent and true refHTN in a real life national registry of an Health Maintenance Organization (HMO). Design and method: In this real-life observational study we utilized the Maccabi Healthcare Services (MHS) database during 2023. Data includes pharmacy prescriptions and purchases. Apparent refHTN was defined as patients included in the Maccabi “Hypertension Registry” during 2023 and taking 5 different antihypertensive medications of different classes, of which four were from pre-specified groups (diuretics, CCB, RAAS inhibitors and MRAs). True refHTN (unlike apparent refHTN) was defined as being fully adherent to the antihypertensive medication regimen with at least 6 prescriptions and purchases (refills) during 2023 as well as blood pressure which was not optimally controlled during the year (less than 80% of blood pressure measurements equal or below the well-defined target of 130/80mmHg). Results: Out of 1,821,685 adult members of Maccabi HMO during 2023, 361,721 patients were defined as hypertensive patients (20%) and included in the registry. 0.5% (1750) of the hypertensive population were at some stage during 2023 on at least 5 anti-hypertensive medications (i.e., apparent refHTN). Of those only 264 patients (15%) were adherent to their medications during the whole year. Mean age was 71.3 years. Of the well adherent group, 205 patients (77%) were not optimally controlled and thus regarded as true refHTN. Therefore in total, true refHTN was evident in 0.056% of hypertensive population in Maccabi HMO. Conclusions: In an “optimal world” which lacks physician inertia, four medication regimen is prescribed (Diuretics, CCB, RAAS inhibitors and MRAs) and there is willingness to prescribe a fifth and a sixth medication, if needed (alpha blockers, beta blockers, central alpha-2 agonists or direct vasodilators). In the unlikely case of full adherence to all medications, true refHTN is extremely rare (0.056% of hypertensive patients). This suggests that most hypertensive patients can be well controlled using the current anti hypertensive armamentarium.

Prediction of cognitive conflict during unexpected robot behavior under different mental workload conditions in a physical human–robot collaboration

Objective. Brain–computer interface (BCI) technology is poised to play a prominent role in modern work environments, especially a collaborative environment where humans and machines work in close proximity, often with physical contact. In a physical human robot collaboration (pHRC), the robot performs complex motion sequences. Any unexpected robot behavior or faulty interaction might raise safety concerns. Error-related potentials, naturally generated by the brain when a human partner perceives an error, have been extensively employed in BCI as implicit human feedback to adapt robot behavior to facilitate a safe and intuitive interaction. However, the integration of BCI technology with error-related potential for robot control demands failure-free integration of highly uncertain electroencephalography (EEG) signals, particularly influenced by the physical and cognitive state of the user. As a higher workload on the user compromises their access to cognitive resources needed for error awareness, it is crucial to study how mental workload variations impact the error awareness as it might raise safety concerns in pHRC. In this study, we aim to study how cognitive workload affects the error awareness of a human user engaged in a pHRC. Approach. We designed a blasting task with an abrasive industrial robot and manipulated the mental workload with a secondary arithmetic task of varying difficulty. EEG data, perceived workload, task and physical performance were recorded from 24 participants moving the robot arm. The error condition was achieved by the unexpected stopping of the robot in 33% of trials. Main results. We observed a diminished amplitude for the prediction error negativity (PEN) and error positivity (Pe), indicating reduced error awareness with increasing mental workload. We further observed an increased frontal theta power and increasing trend in the central alpha and central beta power after the unexpected robot stopping compared to when the robot stopped correctly at the target. We also demonstrate that a popular convolution neural network model, EEGNet, could predict the amplitudes of PEN and Pe from the EEG data prior to the error. Significance. This prediction model could be instrumental in developing an online prediction model that could forewarn the system and operators of the diminished error awareness of the user, alluding to a potential safety breach in error-related potential-based BCI system for pHRC. Therefore, our work paves the way for embracing BCI technology in pHRC to optimally adapt the robot behavior for personalized user experience using real-time brain activity, enriching the quality of the interaction.

Same allocation proposed by an individual or a group elicits distinct responses: Evidence from event-related potentials and neural oscillation

People tend to perceive the same information differently depending on whether it is expressed in an individual or a group frame. It has also been found that the individual (vs. group) frame of expression tends to lead to more charitable giving and greater tolerance of wealth inequality. However, little is known about whether the same resource allocation in social interactions elicits distinct responses depending on proposer type. Using the second-party punishment task, this study examined whether the same allocation from different proposers (individual vs. group) leads to differences in recipient behavior and the neural mechanisms. Behavioral results showed that reaction times were longer in the unfair (vs. fair) condition, and this difference was more pronounced when the proposer was the individual (vs. group). Neural results showed that proposer type (individual vs. group) influenced early automatic processing (indicated by AN1, P2, and central alpha band), middle processing (indicated by MFN and right frontal theta band), and late elaborative processing (indicated by P3 and parietal alpha band) of fairness in resource allocation. These results revealed more attentional resources were captured by the group proposer in the early stage of fairness processing, and more cognitive resources were consumed by processing group-proposed unfair allocations in the late stage, possibly because group proposers are less identifiable than individual proposers. The findings provide behavioral and neural evidence for the effects of “individual/group” framing leading to cognitive differences. They also deliver insights into social governance issues, such as punishing individual and/or group violations.

Oscillatory and non-oscillatory features of the magnetoencephalic sensorimotor rhythm in Parkinson’s disease

Parkinson’s disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early- to mid-stage PD patients (N = 78) on Parkinsonian medication and age- and sex-matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power and central alpha frequency, beta power and central beta frequency, and 1/f broadband characteristics using power spectral density. Furthermore, we characterised transient oscillatory burst events in the mu-beta band time-domain signals. We examined the relationship between these signal features and the patients’ disease state, symptom severity, age, sex, and cortical thickness. PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, the burst rate was associated with increased severity of bradykinesia, whereas the burst duration was associated with axial symptoms. Our study shows that general non-oscillatory features (broadband 1/f exponent and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.

Validity and reliability of self-reported and neural measures of listening effort.

Listening effort can be defined as a measure of cognitive resources used by listeners to perform a listening task. Various methods have been proposed to measure this effort, yet their reliability remains unestablished, a crucial step before their application in research or clinical settings. This study encompassed 32 participants undertaking speech-in-noise tasks across two sessions, approximately a week apart. They listened to sentences and word lists at varying signal-to-noise ratios (SNRs) (-9, -6, -3 and 0dB), then retaining them for roughly 3s. We evaluated the test-retest reliability of self-reported effort ratings, theta (4-7Hz) and alpha (8-13 Hz) oscillatory power, suggested previously as neural markers of listening effort. Additionally, we examined the reliability of correct word percentages. Both relative and absolute reliability were assessed using intraclass correlation coefficients (ICC) and Bland-Altman analysis. We also computed the standard error of measurement (SEM) and smallest detectable change (SDC). Our findings indicated heightened frontal midline theta power for word lists compared to sentences during the retention phase under high SNRs (0dB, -3dB), likely indicating a greater memory load for word lists. We observed SNR's impact on alpha power in the right central region during the listening phase and frontal theta power during the retention phase in sentences. Overall, the reliability analysis demonstrated satisfactory between-session variability for correct words and effort ratings. However, neural measures (frontal midline theta power and right central alpha power) displayed substantial variability, even though group-level outcomes appeared consistent across sessions.

Food-induced brain activity in adult obesity: a quantitative electroencephalographic study

BACKGROUND Obesity may be associated with declined food consumption control through neurological and behavioral processes, as well as heightened responsiveness of the brain’s reward systems. Performing neuroimaging and neurophysiological methods such as electroencephalography (EEG) can examine the connection between brain function and behavior. This study aimed to identify brain regulation of feeding behavior to food cues, which could be a potential neuromodulatory intervention target in adult obesity.&#x0D; METHODS This cross-sectional study was conducted at Cipto Mangunkusumo Hospital, Jakarta, involving 40 adults with obesity. EEG analysis was performed to measure electrophysiological brain activity during eyes-open condition and during exposure to high-calorie food cues. Student’s t-tests were performed to identify any significant differences between the groups (p&lt;0.05).&#x0D; RESULTS Beta waves in the frontal (channel F7) and gamma waves in the central (channels C3 and C4) and parietal (channels P3 and P4) regions were significantly increased during food cues compared to resting state/eyes-open condition without stimulation. Theta waves in the frontal (channels F7 and F8), central (channel C3), and parietal (channels P3 and P4) regions and alpha waves in the central (channels C3 and C4) and parietal (channels P3 and P4) regions were significantly decreased during food cues compared with resting state.&#x0D; CONCLUSIONS In adults with obesity, increased beta activity in the frontal and gamma in the central and parietal regions suggested increased food-cue awareness and heightened attentional focus toward food stimuli. Additionally, decreased alpha and theta activities in frontal regions could underline deficits in executive functions and higher motivation.

Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans

Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD.

Arthroscopy Confers Favorable Clinical Outcomes in Asian Patients with Borderline Developmental Dysplasia of the Hip.

Hip arthroscopy has recently appeared as a successful therapy in treating borderline developmental dysplasia of the hip (BDDH). This study aimed to describe the minimal 2-year follow-up after hip arthroscopy for patients with BDDH in the Asian population and use the combination of lateral center edge angle (LCEA) and alpha angles to detect the appearance of impingement in the BDDH population. This retrospective investigation was conducted utilizing information from arthroscopically treated BDDH patients in 2018 and 2019. The following patient-reported outcomes were reported: modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, International Hip Outcome Tool 12-component form, and Visual Analog Scale. We also considered the clinical data regarding radiological measurements, intraoperative findings, interventions, complications, and subsequent surgical revisions, in the analysis of combination angles in detecting the occurrence of impingement. Patients with asymptomatic contralateral hips from traumatic hip injury (pelvic fracture) served as the control group. A 2:1 propensity score matching was based on age, sex, and BMI. A receiver operating characteristic curve (ROC) was used to identify the thresholds of combination angles and their accuracies. A total of 77 hips met the inclusion and exclusion requirements. After the follow-up period, most patients showed a considerable improvement in patient-reported outcomes compared to their preoperative values (P < 0.001 for all). The overall rate of complications was 5.2%, whereas the rate of revisions was 3.9%. Increasing preoperative alpha angle age was significantly positively correlated with improving patient-reported outcomes. The combined angle cut-off was determined to be 80.5° (AUC, 0.858; 95% CI: 0.757-0.938; sensitivity (SE), 98.1%; specificity (SP), 74.1%; P < 0.001) for the occurrence of impingement in BDDH population. Good patient-reported outcomes and low revision rates can be expected in the BDDH population with careful selection of patients in Asian populations. A combination angle >80.5° could be a reliable predictive factor of impingement in BDDH populations.

Central alpha-2 adrenergic mechanisms affect human sympathetic neuronal discharge strategies

The central neural mechanisms affecting sympathetic neuronal discharge strategies supporting homeostatic adjustments in human muscle sympathetic nerve activity (MSNA) remain unclear. This study investigated the hypothesis that central alpha-2 adrenergic mechanisms affect sympathetic action potential (AP) discharge, recruitment, and latency patterns within human MSNA (peroneal nerve microneurography and continuous wavelet transform). An alpha-2 adrenergic agonist (dexmedetomidine) was infused in eight healthy male and female participants (5 females; 28 ± 7years). Data were recorded during a 5-minute resting control condition, a 10-minute intravenous dexmedetomidine loading dose (0.225 μg/kg), and a dexmedetomidine maintenance dose (~0.1 μg/kg/hr). Data are reported as mean (SD) for the 5-minute control condition and 2-minutes of the dexmedetomidine infusion when MSNA bursting activity was demonstrably reduced. Two-tailed paired t-tests were performed. Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg; P &lt; 0.01) but did not affect heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.75). Dexmedetomidine reduced integrated MSNA burst frequency (14 ± 6 to 4 ± 3 bursts/min; P &lt; 0.01), sympathetic AP frequency (75 ± 46 to 16 ± 14 AP/min; P &lt; 0.01), APs per burst (5 ± 1 to 4 ± 1 AP/burst; P = 0.01), AP clusters per burst (3.5 ± 0.7 to 3.0 ± 0.7 clusters/burst; P = 0.03), and de-recruited the largest AP clusters (12 ± 3 to 7 ± 2 AP clusters; P &lt; 0.01). Despite de-recruiting large AP clusters with short conduction times, dexmedetomidine elicited shorter sympathetic AP conduction times (1.18 ± 0.12 to 1.14 ± 0.13 s; P = 0.03). Six participants performed a Valsalva Maneuver (20 s, 40 mmHg mouth pressure) during the control condition and during the dexmedetomidine maintenance dose. Data are reported as mean (SD) change (Δ) from the 2-minute period preceding the Valsalva Maneuver to the Valsalva Maneuver for each condition. During the control condition, Valsalva Maneuver increased AP frequency (Δ 311 ± 317 AP/min; P = 0.048), recruited larger previously silent AP clusters (Δ 2 ± 1 AP clusters; P &lt; 0.01), and elicited shorter AP conduction times (Δ ‑0.09 ± 0.07 s; P = 0.02). Compared to the control condition, Valsalva Maneuver performed during the dexmedetomidine maintenance dose condition elicited lesser increases in AP frequency (Δ 116 ± 189 AP/min; P vs. control = 0.02) and lesser recruitment of larger previously silent AP clusters (Δ 0 ± 1 AP clusters; P vs. control = 0.02). Dexmedetomidine did not affect the latency reduction elicited by Valsalva Maneuver (Δ ‑0.07 ± 0.14 s; P vs. control = 0.61). These data suggest that human central alpha-2 adrenergic mechanisms affect: i) sympathetic postganglionic neuronal discharge and recruitment patterns, and ii) synaptic delays within the sympathetic neurocircuitry influencing AP latency. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Femoroacetabular Impingement on Hip Fractures

AIM: The aim of this study is to find out if there is a relationship between femoroacetabular syndrome and the risk of hip fractures that have been known with high morbidity and mortality rates.&#x0D; MATERIAL AND METHOD: Between January 1st of 2015 and January 1st of 2020, data of 243 patients with intertrochanteric fracture, 126 patients with femoral neck fracture and 250 trauma patients of over 65 years old that had admitted to our hospital’s emergency department but had no fracture on both pelvis AP x-ray and pelvis CT, were evaluated retrospectively. While central edge angle, acetabular index and singh index were measured on AP x-ray of pelvis, alfa-angle, anterior offset and anterior offset ratio were measured on pelvis CT.&#x0D; RESULTS: No significant differences were found between the groups forming the hip fracture and the control group in terms of gender, age and Singh index, indicating that these factors were homogeneously distributed between the groups and had no effect on the factors investigated (p&gt;0.05). The central edge angle, acetabular index, alpha angle, anterior offset and anterior offset ratio were found to be significantly different (p

Quantitative Electroencephalography Findings in Treatment-resistant and Responsive Patients with Idiopathic Generalized Tonic-Clonic Epilepsy

Background: With roughly 50 million people affected in the world, epilepsy is a particularly important disorder of the brain commonly diagnosed based on findings of quantitative electroencephalography (QEEG). The present investigation was aimed to evaluate differences in QEEG readings of drug-resistant and drug-responsive patients with idiopathic generalized epilepsy (IGE) with tonic-clonic seizures in a northwestern Iranian population.Methods: A total of 60 participants, consisting of 30 drug-resistant and 30 drug-responsive patients with IGE, were enrolled. Data, including demographic information and Z-transformed absolute power values of QEEG in anterior, central, and posterior alpha, beta, delta, and theta bands were collected. The analysis was conducted using IBM SPSS and a p-value<0.05 was considered statistically significant.Results: Of the 60 participants with a mean age of 31.55 ± 10.48, 41 (68.3%) were female and 19 (31.7%) were male. Statistically significant differences were observed in anterior alpha, beta and theta bands, central alpha, beta, delta and theta bands, and posterior beta, delta and theta bands between the two groups, with the absolute power Z-scores of the drug-resistant groups being significantly higher than the other (P-values<0.05). Abnormal EEGs were recorded for 16 (53.3%) and 5 (23.8%) patients from the drug-resistant and drug-response groups, respectively, indicating a significant difference (P-value=0.006). Female patients were more likely to have the drug-resistant disease than male participants (P-value=0.003).Conclusions: QEEGs with normal readings indicate a more favorable prognosis, compared with those containing abnormal findings.

Asenapine as a Potential Lead Inhibitor against Central Ca2+/Calmodulin-Dependent Protein Kinase II: Investigation by Docking Simulation and Experimental Validation

Aim: The aim of this potential repurposing study is to investigate the potential inhibitory activity of asenapine against central nervous system CaMKII isozymes using docking experiments and enzymatic assay. Background: The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional protein kinase ubiquitously expressed throughout the brain. Emerging biological data have indicated that inhibiting central nervous system CaMKII isoforms, namely, CaMKIIα and CaMKIIβ, may be a promising therapeutic strategy for the potential treatment of many neurological diseases including schizophrenia, depression, epilepsy, and learning deficit. Objective: 1- Study the possible attractive interactions of asenapine within the binding sites of the central CaMKII isozymes. 2- Evaluate the inhibitory activities of asenapine against central CaMKII isozymes. Methods: Docking experiments of asenapine and other known CaMKII inhibitors were performed. Docking settings were validated using ROC analysis. After that, the inhibitory activities of asenapine against central CaMKII alpha and beta were evaluated by enzymatic assay. Result: Docking and scoring experiments of asenapine showed several binding interactions anchoring asenapine within CaMKIIα and CaMKIIβ catalytic sites while enzymatic assay results revealed that asenapine can inhibit CaMKIIα and CaMKIIβ in the micromolar range. Conclusion: Our study provides evidence that asenapine can serve as a promising lead for the development of new CaMKIIα and CaMKIIβ inhibitors. Moreover, this study reinforces how the investment in drug repurposing could boost the drug discovery process.

Preparations methods of tizanidine (API) and related compounds: A review

Tizanidine is an imidazoline derivative with the agonistic activity of central alpha 2 receptors at both the spinal and supra-spinal levels. It was prepared for the first time in 1978 and approved for use in 1996. The present review focuses on all methods used for the synthesis of tizanidine, related compounds and intermediates. This review article covers all the methods that have been used in the preparation of tizanidine since its discovery until now. Methods used for the preparation of tizanidine-related compounds are also covered. This review gives those interested in drug synthesis and designs the ability to form a complete picture of the preparation of this drug, as well as providing the opportunity for the synthesis of other drugs developed from this drug to increase activity and/or reduce side effects.

A case series of accidental xylazine intoxication in humans; Is there a role of naloxone as an antidote?

Xylazine is a type of sedative commonly used in veterinary medicine. It acts on the central alpha-2 receptor and suppresses norepinephrine release from the peripheral nerve terminal. It is also reported to have action on cholinergic, serotogenic, H2-histamine, dopaminergic, and opioid receptors. Once administered in animals, it causes hypotension, bradycardia, central nervous system depression, and respiratory depression. The effect will start within minutes after absorption and last up to 4 h depending on the dosage given. Till date, it is only exclusively used in animals as approved by the Food and Drug Administration. Human intoxication is uncommon, and no specific antidote is available. Naloxone, a competitive opioid receptor antagonist, was postulated to have an antidotal effect on xylazine. We report two cases of accidental human injection with xylazine. Naloxone was administered in one of the cases. Acute hypertension and mydriasis were observed; however, no apparent reversal of toxidrome was seen. This finding reveals the question regarding the efficacy and benefit of naloxone usage in xylazine intoxication. General management remains supportive of care focusing on ventilation and hemodynamics. Attending physicians should be aware of potential xylazine intoxication incidents in the area of livestock or veterinary activities.

682: UNINTENTIONAL PEDIATRIC ORAL INGESTION OF BRIMONIDINE EYE DROPS

Introduction: Brimonidine is a central alpha-2 adrenergic agonist agent chemically similar to clonidine. When used for glaucoma treatment, activation of alpha-2 receptors in the ciliary musculature culminates in decreased intraocular pressure by reducing aqueous humor production and stimulating outflow. While intended use is intraocular, oral ingestion and associated neurological and cardiovascular toxicities are not robustly documented in pediatric literature. In this case report, we present the toxic oral ingestion of brimonidine eye drops in a pediatric patient. Description: A two year old, previously healthy female presented to the emergency department (ED) with acute altered mental status, found dizzy and unresponsive by her grandmother around 9pm; she was last known well before going to bed at 8pm. On arrival to the ED, the patient was crying, intermittently somnolent, and opening her eyes spontaneously. Her vital signs were as follows: temperature 97.2F, heart rate 79 beats per minute, respiratory rate 22 time per minute, blood pressure 126/86 mmHg. Venous blood gas showed respiratory alkalosis and lactate 2.1mmol/L. A urine toxicology screen was negative and serum acetaminophen, salicylate, alcohol, and tricyclic levels were undetectable. Head imaging and electrocardiograms were normal. Upon further review, the patient’s grandmother revealed she recently underwent kidney transplantation. She detailed that none of her oral medications were missing but had found an empty bottle of brimonidine eye drops under the couch. The grandmother was unable to share whether it was a 5mL or 15mL bottle of 0.1% or 0.2% eye drops. With concern that the patient may have ingested brimonidine, she received empiric intravenous naloxone 0.1mg/kg amounting to 1.5mg. Rapid improvement in wakefulness and mental status was observed. The child was admitted for monitoring in an intensive care unit, did not require any additional naloxone, and was discharged after approximately 36 hours. Discussion: Oral ingestion of brimonidine eye drops may cause somnolence and bradycardia in pediatric patients. Additionally, naloxone utilization may not elicit an appropriate response. This case describes the successful identification of toxicity and use of empiric naloxone for diagnostic and treatment purposes in a pediatric patient.

Action experience in infancy predicts visual-motor functional connectivity during action anticipation.

Despite substantial evidence indicating a close link between action production and perception in early child development, less is known about how action experience shapes the processes of perceiving and anticipating others' actions. Here, we developed a novel approach to capture functional connectivity specific to certain brain areas to investigate how action experience changes the networks involved in action perception and anticipation. Nine- and-12-month-old infants observed familiar (grasping) and novel (tool-use) actions while their brain activity was measured using EEG. Infants' motor competence of both actions was assessed. A link between action experience and connectivity patterns was found, particularly during the anticipation period. During action anticipation, greater motor competence in grasping predicted greater functional connectivity between visual (occipital alpha) and motor (central alpha) regions relative to global levels of whole-brain EEG connectivity. Furthermore, visual and motor regions tended to be more coordinated in response to familiar versus novel actions and for older than younger participants. Critically, these effects were not found in the control networks (frontal-central; frontal-occipital; parietal-central; parietal-occipital), suggesting a unique role of visual-motor networks on the link between motor skills and action encoding. HIGHLIGHTS: Infants' motor development predicted functional connectivity patterns during action anticipation. Faster graspers, and older infants, showed a stronger ratio of visual-motor neural coherence. Overall whole-brain connectivity was modulated by age and familiarity with the actions. Measuring inter-site relative to whole-brain connectivity can capture specific brain-behavior links. Measures of phase-based connectivity over time are sensitive to anticipatory action.