Changes In Activity Patterns Research Articles

The effects of locus coeruleus optogenetic stimulation on global spatiotemporal patterns in rats

Abstract Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. We hypothesize that localized effects could be due to engagement of LC modules that support behaviors induced by our specific stimulation parameters, in addition to noradrenergic receptor profile distributions. Nonetheless, these results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting, further supporting emerging evidence of a modular LC.

Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer.

Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case-control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3months until study termination. Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. EUPAS9462. Registered 30th October 2012 "retrospectively registered."

Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Older Veterans: Protocol for a Randomized Controlled Trial.

Growing health care challenges resulting from a rapidly expanding aging population necessitate examining effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence. This work aims to implement a multimodal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise-induced adaptations to sedentary older adults' brains and behaviors. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise-induced changes to cerebral perfusion, cerebral vascular reactivity (CVR), and cognitive and sensorimotor task-dependent functional magnetic resonance imaging (fMRI) after prescribed exercise. Sedentary older adults (aged 65-80 years) were randomly assigned to either a 12-week aerobic-based interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness used the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, and cortical activation using fMRI during verbal fluency and motor tapping tasks. A battery of cognitive-executive and motor function tasks outside the scanning environment will be performed before and after the interventions. Our studies and others show that improved cardiovascular fitness in older adults results in improved outcomes related to physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI, which corresponds with improved task performance (cognitive-executive and motor). We hypothesize that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR through a greater magnitude of reactivity in brain areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To differentiate between neural and vascular adaptations in these regions, we will map changes in basal perfusion and CVR over the inferior frontal and the motor cortices-regions we have previously shown to be beneficially altered during fMRI BOLD (blood oxygen level dependent), such as verbal fluency and motor tapping, through improved cardiovascular fitness. Exercise is one of the most impactful interventions for improving physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention is supported, it would add critically important insights into the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction. ClinicalTrials.gov NCT05932069; https://clinicaltrials.gov/study/NCT05932069. DERR1-10.2196/58316.

Pairing tones with vagus nerve stimulation improves brain stem responses to speech in the valproic acid model of autism.

Receptive language deficits and aberrant auditory processing are often observed in individuals with autism spectrum disorders (ASD). Symptoms associated with ASD are observed in rodents prenatally exposed to valproic acid (VPA), including deficits in speech sound discrimination ability. These perceptual difficulties are accompanied by changes in neural activity patterns. In both cortical and subcortical levels of the auditory pathway, VPA-exposed rats have impaired responses to speech sounds. Developing a method to improve these neural deficits throughout the auditory pathway is necessary. The purpose of this study was to investigate the ability of vagus nerve stimulation (VNS) paired with sounds to restore degraded inferior colliculus (IC) responses in VPA-exposed rats. VNS paired with the speech sound "dad" was presented to a group of VPA-exposed rats 300 times per day for 20 days. Another group of VPA-exposed rats were presented with VNS paired with multiple tone frequencies for 20 days. The IC responses were recorded from 19 saline-exposed control rats and 18 VPA-exposed with no VNS, 8 VNS-speech paired VPA-exposed, and 7 VNS-tone paired VPA-exposed female and male rats. Pairing VNS with tones increased the IC response strength to speech sounds by 44% compared to VPA-exposed rats alone. Contrarily, VNS-speech pairing significantly decreased the IC response to speech compared with VPA-exposed rats by 5%. The present research indicates that pairing VNS with tones improved sound processing in rats exposed to VPA and suggests that auditory processing can be improved through targeted plasticity.NEW & NOTEWORTHY Pairing vagus nerve stimulation (VNS) with sounds has improved auditory processing in the auditory cortex of normal-hearing rats and autism models of rats. This study tests the ability of VNS-sound pairing to restore auditory processing in the inferior colliculus (IC) of valproic acid (VPA)-exposed rats. Pairing VNS with tones significantly reversed the degraded sound processing in the IC in VPA-exposed rats. The findings provide evidence that auditory processing in autism rat models can be improved through VNS.

Unveiling mobility patterns beyond home/work activities: A topic modeling approach using transit smart card and land-use data

In this paper, a probabilistic topic modeling algorithm called Latent Dirichlet Allocation (LDA) is implemented to infer trip purposes from activity attributes revealed from smart card transit data in an unsupervised manner. While most literature focused on finding patterns for home and work activities, we further investigated non-home and non-work-related activities to detect patterns associated with them. Temporal attributes of activities are extracted from trip information recorded by Tehran subway’s automatic fare collection system. In addition, land-use data is also incorporated to further enhance spatial attributes for non-home/work activities. Various activity attributes such as start time, duration, and frequency in addition to land-use data are used to infer the activity purposes and patterns. We identified 14 different patterns related to non-commuting activities on the basis of both their temporal and spatial attributes including educational, recreational, commercial, and health and other service-related activity types. We investigated passengers’ activity pattern and behavior changes before and during COVID-19 pandemic by comparing the discovered patterns. For recreational patterns it is revealed that not only has the number of recreational patterns dropped, but also the duration of recreational activities decreased. Morning patterns of educational activities have also been eliminated and number of commercial activities was decreased during COVID-19. The proposed model demonstrates the ability to capture travel behavior changes for different disruptions using smart card transit data without performing costly and time consuming manual surveys which can be useful for authorties and decision makers.

Spontaneous termination of ventricular tachycardia in the human heart.

Understanding the spatiotemporal location of the spontaneous termination of ventricular tachycardia (VT) may provide new insights for ablation. To test the hypothesis that spontaneous VT termination most frequently occurs at the VT exit due to source-sink mismatch and to characterize electrophysiological properties of the sites termination during VT and with extra-stimulus technique. Retrospective analysis of intraoperative mapping studies of nine patients with ischemic cardiopathy or repaired tetralogy of Fallot. Simultaneous endocardial and epicardial mapping was performed in both ventricles using a custom mapping array during VT. Electrogram (EGM) characteristics before and at the moment of termination were analyzed including: cycle length oscillations, EGM heterogeneity and a variation in the systolic/diastolic path. The decrements to extra stimulus were analysed for termination sites and other diastolic sites. Nine VTs in seven patients demonstrated spontaneous VT termination. Seven VTs (77.8%) spontaneously terminated in the final third of the systolic interval, one (11.1%) in early diastole and one (11.1%) in mid diastole. Cycle length oscillations (prolongation, shortening, and no change) were seen in equal frequency. Four VTs (44.4%) showed alternans in the local EGM at the site of termination and this was more prevalent than alternans at other sites in the diastolic pathway (p < .001). Only one-third of VTs showed a change in activation pattern before termination. There was no difference based on etiology. During substrate characterization with extra-stimulus pacing, sites of spontaneous termination showed greater decrement than other sites of the VT circuit during pacing (43.5 ± 14.5 ms vs. 31.2 ± 31.2 ms; p = .003). The entrance zone rather than the exit is the commonest site for the spontaneous termination of VT in the human heart. These sites tend to demonstrate EGM alternans during VT and greater decrement during extrastimulus pacing. These findings may help guide future studies into improving the success of VT ablation.

Evolving Dynamics of Neck Muscle Activation Patterns in Dental Students: A Longitudinal Study.

Cervical pain has been linked to increased motor unit activity, potentially associated with the initiation and progression of chronic neck pain. Therefore, this study aimed to compare the time-course changes in cervical superficial muscle activation patterns among dental students with and without neck pain throughout their initial semester of clinical training. We used an online Nordic Musculoskeletal Questionnaire for group allocation between neck pain (NP) (n = 21) and control group (CG) (n = 23). Surface electromyography (sEMG) of the sternocleidomastoid and upper bilateral trapezius was recorded before starting their clinical practice and after their first semester while performing a cranio-cervical flexion test (CCFT) in five increasing levels between 22 mmHg and 30 mmHg. After the first semester, both the CG (p < 0.001) and NP (p = 0.038) groups showed decreased sternocleidomastoid activation. The NP group exhibited a concomitant increase in upper trapezius coactivation (p < 0.001), whereas the muscle activation pattern in asymptomatic students remained unchanged (p = 0.980). During the first semester of clinical training, dental students exhibited decreased superficial flexor activity, but those with neck pain had increased co-contraction of the upper trapezius, likely to stabilize the painful segment. This altered activation pattern could be associated with further dysfunction and symptoms, potentially contributing to chronicity.

Aerobic exercise elevates perceived appetite but does not modify energy intake over a 3-day postexercise period: A pilot study.

While a low degree of energy compensation is typically reported over the 24 h following a session of exercise, the prolonged impact of a bout of exercise on energy intake remains unclear. To overcome the challenge associated with accurately measuring energy intake in a free-living environment, this study employed the use of a meal replacement beverage to assess the 3 day impact of an exercise session on energy intake. In a randomized, crossover study, 14 participants (8 male, 6 female) completed two trials: (1) EX: 75 min exercise on a motorized treadmill (75% VO2peak); and (2) SED: 75 min sedentary control session. Each condition was followed by 3 days of exclusive adlibitum consumption of a meal replacement beverage. Appetite-regulating hormones, subjective appetite, energy intake, and energy expenditure were assessed. Exercise transiently suppressed the orexigenic hormone acyl-ghrelin (p < 0.05) and elevated the appetite-supressing hepatokine GDF-15 (p < 0.05). Despite these acute changes, overall perceived appetite was elevated over the 3 day assessment period with exercise (p < 0.05). No increase in energy intake or change in postexercise physical activity patterns were observed. One acute session of moderate to vigorous exercise is unlikely to affect short-term, three-day energy balance in healthy individuals.

Effects of Head-Only Exposure to 900 MHz GSM Electromagnetic Fields in Rats: Changes in Neuronal Activity as Revealed by c-Fos Imaging without Concomitant Cognitive Impairments.

Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here.

Mindfulness-enhancing instruction (MEI): Contributions to electroencephalogram (EEG) Dynamics, Higher Order Thinking Skills (HOTS), and effective learning

The current study examined the role of mindfulness-enhancing instruction (MEI) in university students’ Electroencephalogram (EEG) dynamics, Higher Order Thinking Skills (HOTS), and effective learning. In so doing, 60 junior university students, being screened out of 72 available sample, were randomly assigned into two groups. MEI was incorporated into class activities of the experimental group during the term. A package containing a host of activities was devised, integrating general meditation practices with educational MEI. These in-class activities were complemented with daily at-home practices offered by a mobile application. To assess participants’ level of HOTS, two tests from the “Watson-Glaser Critical Thinking Appraisal” (CTA) (Form A) was utilized. In this study, inference and deduction modules were included. The participants responded to the tests while they were involved in EEG acquisition. The results of statistical analysis demonstrated the efficiency of the implemented MEI in enhancing two dimensions of HOTS (inference-making & deduction) as well as academic achievement. The EEG analysis demonstrated notable changes in the experimental group's brain activity patterns. Specifically, there was a significant decrease in the ratio of energy in the alpha to beta frequency band (α/β ratio) for Fp1 and Fp2 channels post-meditation, indicative of heightened attentiveness. Conversely, the control group exhibited less pronounced changes in the EEG measures.

Selective complex fractionated atrial electrogram ablation based on the number-of-fractionation for persistent atrial fibrillation refractory to pulmonary vein isolation.

Previous studies have suggested that the prolonged or highly fractionated electrograms during atrial fibrillation (AF) are closely related to the reentrant driver regions. We hypothesized that exploration and ablation of these critical complex atrial fractionated electrograms (CFAE) may improve the outcome of persistent AF (PeAF) refractory to conventional PVI. A total of 73 PeAF patients with residual inducibility or failed cardioversions of AF after PVI were enrolled and underwent number-of-fractionation mapping (NFM) by counting the number of fractionations in 2.5s at each of the points using the CARTO3 (ICL mode) and EnSite (fractionation map) systems. After NFM, selective CFAE ablation (NFM-CA) targeting the sites of the upper 40% of the counted fraction number (NF40) was performed as an additional procedure for refractory PeAF. We investigated the prognosis of these patients within 24months after the index ablation procedure and the relationship between changes in activation patterns during the ablation procedure and their prognosis. We also performed a propensity score-matched analysis comparing these patients with historical controls (HC) to identify the optimal indications for NFM-CA. The AF/AT free survival rate was 79.1% at 12months and 56.7% at 24months. Patients with AF termination or AF cycle length prolongation > 21ms during the procedure had significantly better AF/AT-free survival rates than those without notable activation changes (87.7% vs. 69.0%, logrank p = 0.028). After propensity-matched analysis, AF/AT-free survival showed comparable results between the two groups (1year; NFM 72.1% vs. HC 77.1%, logrank p = 0.649). NFM-CA is a versatile and less invasive adjunctive procedure for patients with PVI-refractory PeAF who showed a comparable prognosis to patients with PVI-compliant PeAF. In particular, remarkable activation changes during the procedure (AFCL prolongation > 21ms or acute termination) suggest a favorable prognosis.

Analysis of stress response distribution in patients with lateral ankle ligament injuries: a study of neural control strategies utilizing predictive computing models.

Ankle sprains are prevalent in sports, often causing complex injuries to the lateral ligaments. Among these, anterior talofibular ligament (ATFL) injuries constitute 85%, and calcaneofibular ligament (CFL) injuries comprise 35%. Despite conservative treatment, some ankle sprain patients develop chronic lateral ankle instability (CLAI). Thus, this study aimed to investigate stress response and neural control alterations during landing in lateral ankle ligament injury patients. This study recruited twenty individuals from a Healthy group and twenty CLAI patients performed a landing task using relevant instruments to collect biomechanical data. The study constructed a finite element (FE) foot model to examine stress responses in the presence of laxity of the lateral ankle ligaments. The lateral ankle ligament was modeled as a hyperelastic composite structure with a refined representation of collagen bundles and ligament laxity was simulated by adjusting material parameters. Finally, the validity of the finite element model is verified by a high-speed dual fluoroscopic imaging system (DFIS). CLAI patients exhibited earlier Vastus medialis (p < 0.001) and tibialis anterior (p < 0.001) muscle activation during landing. The FE analysis revealed that with laxity in the ATFL, the peak von Mises stress in the fifth metatarsal was 20.74MPa, while with laxity in the CFL, it was 17.52MPa. However, when both ligaments were relaxed simultaneously, the peak von Mises stress surged to 21.93MPa. When the ATFL exhibits laxity, the CFL is subjected to a higher stress of 3.84MPa. Conversely, when the CFL displays laxity, the ATFL experiences a peak von Mises stress of 2.34MPa. This study found that changes in the laxity of the ATFL and the CFL are linked to shifts in metatarsal stress levels, potentially affecting ankle joint stability. These alterations may contribute to the progression towards CLAI in individuals with posterolateral ankle ligament injuries. Additionally, significant muscle activation pattern changes were observed in CLAI patients, suggesting altered neural control strategies post-ankle ligament injury.

Neural correlates of approach–avoidance behavior in healthy subjects: Effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex

The dorsolateral prefrontal cortex (dlPFC) is implicated in top-down regulation of emotion, but the detailed network mechanisms require further elucidation. To investigate network-level functions of the dlPFC in emotion regulation, this study measured changes in task-based activation, resting-state and task-based functional connectivity (FC) patterns following suppression of dlPFC excitability by 1-Hz repetitive transcranial magnetic stimulation (rTMS). In a sham-controlled within-subject design, 1-Hz active or sham rTMS was applied to the right dlPFC of 19 healthy volunteers during two separate counterbalanced sessions. Following active and sham rTMS, functional magnetic resonance imaging (fMRI) was conducted in the resting state (rs-fMRI) and during approach–avoidance task responses to pictures with positive and negative emotional content (task-based fMRI). Activation and generalized psychophysiological interaction analyses were performed on task-based fMRI, and seed-based FC analysis was applied to rs-fMRI data. Task-based fMRI revealed greater and more lateralized activation in the right hemisphere during negative picture responses compared to positive picture responses. After active rTMS, greater activation was observed in the left middle prefrontal cortex compared to sham rTMS. Further, rTMS reduced response times and error rates in approach to positive pictures compared to negative pictures. Significant FC changes due to rTMS were observed predominantly in the frontoparietal network (FPN) and visual network (VN) during the task, and in the default mode network (DMN) and VN at rest. Suppression of right dlPFC activity by 1-Hz rTMS alters large-scale neural networks and modulates emotion, supporting potential applications for the treatment of mood disorders.

Cost-benefit Tradeoff Mediates the Rule- to Memory-based Processing Transition during Practice.

Practice not only improves task performance, but also changes task execution from rule- to memory-based processing by incorporating experiences from practice. However, how and when this change occurs is unclear. We tested the hypothesis that strategy transition in task learning results from cost-benefit analysis. Participants learned two task sequences and were then queried about the task type at a cued sequence and position. Behavioral improvement with practice can be accounted for by a computational model implementing cost-benefit analysis. Model-predicted strategy transition points are related to behavioral slowing and changes in fMRI activation patterns in the dorsolateral prefrontal cortex. Strategy transition is also related to increased pattern separation in the ventromedial prefrontal cortex. The cost-benefit analysis model outperforms alternative models (e.g., both strategies racing for being expressed in behavior) in accounting for empirical data. These findings support cost-benefit analysis as a mechanism of practice-induced strategy shift.

Neural Functioning in Late-Life Depression: An Activation Likelihood Estimation Meta-Analysis.

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico-limbic-striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico-striatal-cerebellar network in the neurophysiopathology of LLD.

Changes in frontal cortex hemodynamic activity in a patient with schizophrenia undergoing electroconvulsive therapy – case analysis using functional near-infrared spectroscopy (fNIRS)

Introduction: In recent years, one of the most interesting areas of research is the change in hemodynamic response of the prefrontal cortex as a predictor of response to electroconvulsive treatments (ECT). Near-infrared spectroscopy (fNIRS) is non -invasive functional neuroimaging technique that allows the assessment of neuronal activity in frontotemporal regions. The goal of our study was to verify feasibility of fNIRS method to monitor potential changes in frontal cortex hemodynamic activity as a response to ECT treatment. Material and method: The 30 years old, patient with schizophrenia was admitted to the Department of Psychiatry, Psychotherapy and Early Intervention in Lublin for psychiatric treatment. Due to the incomplete therapeutic effect, after using clozapine and electroconvulsive therapy was performed. To monitor the activity of the brain functional fNIRS technique was used. The hemodynamic response of the frontal cortex during performance was assessed: verbal and non-verbal fluency tasks. The Positive and Negative Symptoms Scale was used twice before and after ECT. Results: As a result of pharmacotherapy and electroconvulsive treatment, clinical improvement was achieved, but full remission was not achieved. Evaluation of HbO and Hb fluctuations from one channel showed that the hemodynamic activity of the frontal cortex was opposite to the standard at the time of task initiation. After a series of treatments, the pattern of activity reversed in a more normative direction for figural fluency. Discussion: It appears that the data provided indicate that fNIRS neuroimaging may be a useful tool in monitoring changes in cortical activity patterns in response to therapeutic stimulation such as ECT. Keywords: ECT, fNIRS, schizophrenia

Pain and subjective well-being among older adults in the developing world : A comprehensive assessment based on the WHO Study on Global Ageing and Adult Health

This paper studies the association of pain with subjective well-being (SWB) and time use among older adults in five low- and middle-income countries using data from the first wave of the WHO Study on Global Ageing and Adult Health. We suggest a novel use of anchoring vignettes as direct control functions to account for potentially correlated reporting behaviors such as correlated response scales when analyzing the relationship between subjective variables such as self-reported pain and SWB. Exploiting detailed data on individual time use and several complementary measures of SWB, including fine-grained activity-specific affective experiences derived from an abbreviated version of the Day Reconstruction Method, we find that both evaluative and experienced well-being are markedly lower for people living with pain compared to those without pain. These disparities persist even after controlling for possible confounding from reporting behaviors through the use of anchoring vignettes. Differences in experienced utility by pain status appear to be exclusively due to worse affective experiences during daily activities for those with pain, which seem to be partially mediated through changes in their functional limitations. Pain-related differences in time use, in turn, seem to provide only small compensating effects, underscoring important challenges to the use of changed activity patterns as a viable coping strategy for individuals enduring pain.

Early Marriage Phenomena in Pandemic Era at Luwu Utara, Indonesia

The impact of the Covid-19 pandemic has affected every aspect of life. Not only the decline in the economic situation, but it has also had an impact on the emergence of social problems such as the high rate of early marriage. Early marriage has been a scientific concern for a long time. However, scientific studies have not been able to reduce the rate of increase in the number of children marrying early. The loss of the rights of children who should receive proper education, play and the right to protection are forced to be “bound” in a marriage. The purpose of this article is to add references to solving the problem of early marriage which has been long problematic on an international, national and regional scale. This article discusses the objective conditions of early marriage during a pandemic and criticizes the implementation of strategies for preventing and handling cases of the early child marriage. The data in this study were taken from the main data in the form of in-depth interviews with competent informants. Additional data was taken from existing data at the related office in North Luwu Regency along with the news from online sites, became a reference in this article. This study establish that the number of early marriages has rising due to the widespread use of social networks and changes in daily activity patterns. For future studies, it is recommended to consider the determinant factors in different locations and in a wider scope.

HCN2-based biological pacing in a modified rat AV-block model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Eurostars - Heartpace 114245 Background Electronic pacemakers have several important shortcomings which are difficult to overcome due to their hardware-based design. Gene therapy-based biological pacemakers may provide a different platform which can overcome these limitations. Such biological pacemaker strategies center around overexpression of the pacemaker ion channel HCN2, either alone or with other transgenes to potentiate pacemaker performance, such as the skeletal muscle sodium channel SkM1. In order to develop clinically applicable pacemaker gene therapies further engineering is needed, which would benefit from a reliable small animal model. At present it is unknown if the rat AV block model can be used to evaluate ion channel-based biological pacing. Aim In the present study, we aim to validate a modified rat AV-block model for the evaluation of HCN2 and SKM1-based biological pacing. Methods AV-block was generated in female rats by epicardially applied needle ablation of the AV-nodal region, as previously described (N.K. ). Complete AV-block was confirmed 7 days post-ablation by loss of P-wave and QRS-complex association on the body surface ECG. Seven days post-ablation, 3 groups of animals were injected into the left ventricular apex with Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline (control). 14 days post-ablation, ECG analysis was performed during anesthesia under baseline and after i.v. administration of isoprenaline. Upon completion of functional testing, tissue samples were harvested followed by gene expression analysis using qPCR. Results Injection of Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline did not result in ectopic activation patterns in baseline conditions 7 days after injection. Administration of isoprenaline results in reversal of the QRS complexes 90% of total measurement time in Ad5-TNNT2-HCN2 injected animals. Saline and Ad5-TNNT2-SkM1 showed no change in activation pattern upon isoprenaline administration. Gene expression analysis revealed expression of HCN2 in the injection site following Ad5-TNNT2-HCN2 injection, with minimal spread to non-target regions. However, this analysis also showed Ad5-TNNT2-SkM1 did not express well in this context. Conclusion Our modified rat AV-block model, when administered with isoprenaline, recapitulated expected biological pacemaker activity of HCN2 gene delivery. However, lack of effective expression of SkM1 renders direct comparison of these relevant transgenes difficult. Nevertheless, we expect this rat AV-block model can provide a valuable tool for the evaluation of novel ion channel-based biological pacemaker strategies.

The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats.

Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. These results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting.