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1.
PeerJ Comput Sci ; 10: e2049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983209

RESUMO

Time synchronization among smart city nodes is critical for proper functioning and coordinating various smart city systems and applications. It ensures that different devices and systems in the smart city network are synchronized and all the data generated by these devices is consistent and accurate. Synchronization methods in smart cities use multiple timestamp exchanges for time skew correction. The Skew Integrated Timestamp (SIT) proposed here uses a timestamp, which has time skew calculated from the physical layer and uses just one timestamp to synchronize. The result from the experiment suggests that SIT can be used in place of multiple timestamp exchanges, which saves computational resources and energy.

2.
Sci Rep ; 14(1): 15479, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969743

RESUMO

Most organisms possess three biological oscillators, circadian clock, cell cycle, and redox rhythm, which are autonomous but interact each other. However, whether their interactions and autonomy are beneficial for organisms remains unclear. Here, we modeled a coupled oscillator system where each oscillator affected the phase of the other oscillators. We found that multiple types of coupling prevent a high H2O2 level in cells at M phase. Consequently, we hypothesized a high H2O2 sensitivity at the M phase and found that moderate coupling reduced cell damage due to oxidative stress by generating appropriate phase relationships between three rhythms, whereas strong coupling resulted in an elevated cell damage by increasing the average H2O2 level and disrupted the cell cycle. Furthermore, the multicellularity model revealed that phase variations among cells confer flexibility in synchronization with environments at the expense of adaptability to the optimal environment. Thus, both autonomy and synchrony among the oscillators are important for coordinating their phase relationships to minimize oxidative stress, and couplings balance them depending on environments.


Assuntos
Ciclo Celular , Ritmo Circadiano , Peróxido de Hidrogênio , Modelos Biológicos , Oxirredução , Estresse Oxidativo , Peróxido de Hidrogênio/metabolismo , Ritmo Circadiano/fisiologia , Relógios Circadianos/fisiologia , Animais
3.
Sci Rep ; 14(1): 15741, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977822

RESUMO

Rhythmic entrainment is a fundamental aspect of musical behavior, but the skills required to accurately synchronize movement to the beat seem to develop over many years. Motion capture studies of corporeal synchronization have shown immature abilities to lock in to the beat in children before age 5, and reliable synchronization ability in adults without musical training; yet there is a lack of data on full-body synchronization skills between early childhood and adulthood. To document typical rhythmic synchronization during middle childhood, we used a wireless motion capture device to measure period- and phase-locking of full body movement to rhythm and metronome stimuli in 6 to 11 year-old children in comparison with adult data. Results show a gradual improvement with age; however children's performance did not reach adult levels by age 12, suggesting that these skills continue to develop during adolescence. Our results suggest that in the absence of specific music training, full-body rhythmic entrainment skills improve gradually during middle childhood, and provide metrics for examining the continued maturation of these skills during adolescence.


Assuntos
Música , Humanos , Criança , Masculino , Feminino , Desenvolvimento Infantil/fisiologia , Periodicidade , Adulto , Movimento/fisiologia , Adolescente
4.
Math Biosci ; : 109245, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969059

RESUMO

Synchronization is one of the most striking instances of collective behavior, occurring in many natural phenomena. For example, in some ant species, ants are inactive within the nest most of the time, but their bursts of activity are highly synchronized and involve the entire nest population. Here we revisit a simulation model that generates this synchronized rhythmic activity through autocatalytic behavior, i.e., active ants can activate inactive ants, followed by a period of rest. We derive a set of delay differential equations that provide an accurate description of the simulations for large ant colonies. Analysis of the fixed-point solutions, complemented by numerical integration of the equations, indicates the existence of stable limit-cycle solutions when the rest period is greater than a threshold and the event of spontaneous activation of inactive ants is very unlikely, so that most of the arousal of ants is done by active ants. Furthermore, we argue that the persistent oscillations observed in the simulations for colonies of finite size are due to resonant amplification of demographic noise.

5.
BMC Bioinformatics ; 25(1): 227, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956454

RESUMO

BACKGROUND: Multivariate synchronization index (MSI) has been successfully applied for frequency detection in steady state visual evoked potential (SSVEP) based brain-computer interface (BCI) systems. However, the standard MSI algorithm and its variants cannot simultaneously take full advantage of the time-local structure and the harmonic components in SSVEP signals, which are both crucial for frequency detection performance. To overcome the limitation, we propose a novel filter bank temporally local MSI (FBTMSI) algorithm to further improve SSVEP frequency detection accuracy. The method explicitly utilizes the temporal information of signal for covariance matrix estimation and employs filter bank decomposition to exploits SSVEP-related harmonic components. RESULTS: We employed the cross-validation strategy on the public Benchmark dataset to optimize the parameters and evaluate the performance of the FBTMSI algorithm. Experimental results show that FBTMSI outperforms the standard MSI, temporally local MSI (TMSI) and filter bank driven MSI (FBMSI) algorithms across multiple experimental settings. In the case of data length of one second, the average accuracy of FBTMSI is 9.85% and 3.15% higher than that of the FBMSI and the TMSI, respectively. CONCLUSIONS: The promising results demonstrate the effectiveness of the FBTMSI algorithm for frequency recognition and show its potential in SSVEP-based BCI applications.


Assuntos
Algoritmos , Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Humanos , Potenciais Evocados Visuais/fisiologia , Eletroencefalografia/métodos , Processamento de Sinais Assistido por Computador
6.
Front Netw Physiol ; 4: 1399352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962160

RESUMO

Physiological networks are usually made of a large number of biological oscillators evolving on a multitude of different timescales. Phase oscillators are particularly useful in the modelling of the synchronization dynamics of such systems. If the coupling is strong enough compared to the heterogeneity of the internal parameters, synchronized states might emerge where phase oscillators start to behave coherently. Here, we focus on the case where synchronized oscillators are divided into a fast and a slow component so that the two subsets evolve on separated timescales. We assess the resilience of the slow component by, first, reducing the dynamics of the fast one using Mori-Zwanzig formalism. Second, we evaluate the variance of the phase deviations when the oscillators in the two components are subject to noise with possibly distinct correlation times. From the general expression for the variance, we consider specific network structures and show how the noise transmission between the fast and slow components is affected. Interestingly, we find that oscillators that are among the most robust when there is only a single timescale, might become the most vulnerable when the system undergoes a timescale separation. We also find that layered networks seem to be insensitive to such timescale separations.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38959873

RESUMO

OBJECTIVE: Recent innovative neurostimulators allow recording local field potentials (LFPs) while performing motor tasks monitored by wearable sensors. Inertial sensors can provide quantitative measures of motor impairment in people with subthalamic nucleus deep brain stimulation. To the best of our knowledge, there is no validated method to synchronize inertial sensors and neurostimulators without an additional device. This study aims to define a new synchronization method to analyze disease-related brain activity patterns during specific motor tasks and evaluate how LFPs are affected by stimulation and medication. Approach: Twelve male subjects treated with subthalamic nucleus deep brain stimulation were recruited to perform motor tasks in four different medication and stimulation conditions. In each condition, a synchronization protocol was performed consisting of taps on the implanted device, which produces artifacts in the LFPs that an inertial sensor can simultaneously record. Main results: In 64% of the recruited subjects, induced artifacts were detected at least once. Among those subjects, 83% of the recordings could be correctly synchronized offline. The remaining recordings were synchronized by video analysis. Significance: The proposed synchronization method does not require an external system and can be easily integrated into clinical practice. The procedure is simple and can be carried out in a short time. A proper and simple synchronization will also be useful to analyze subthalamic neural activity in the presence of specific events (e.g., freezing of gait events) to identify predictive biomarkers. .

8.
Percept Mot Skills ; : 315125241262547, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38876089

RESUMO

Our primary purpose in this study was to determine whether trained dancers differed from untrained non-dancers in their ability to accurately control motor timing during finger and heel tapping tasks, both with and without slow isochronous auditory stimuli. Dancers and non-dancers were instructed to synchronize their taps with isochronous auditory stimuli under three conditions: 30, 40, and 50 BPM. After the synchronization phase, participants were asked to continue tapping without the auditory sequences. On the synchronization task, the tapping onset of both groups lagged behind the stimulus onset in all tempo conditions. In all conditions, dancers showed more accurate and stable beat synchronization and continuation than non-dancers. As the tempo condition slowed down (from 50 to 30 BPM), synchronization accuracy decreased while synchronization and continuation variability increased. Unlike for novices, dancers showed no difference between the finger and heel tapping synchronization tasks. During the continuous tasks, their timing accuracy was higher for heel than for finger tapping. Collectively, these findings suggest that dance training, which involves synchronizing bodily movements based on rhythm, may lead to an accumulation of experience that enhances specific sensorimotor skills related to synchronizing movements with external stimuli or continuing rhythmic movements temporally.

9.
Elife ; 122024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904659

RESUMO

Dynamic attending theory proposes that the ability to track temporal cues in the auditory environment is governed by entrainment, the synchronization between internal oscillations and regularities in external auditory signals. Here, we focused on two key properties of internal oscillators: their preferred rate, the default rate in the absence of any input; and their flexibility, how they adapt to changes in rhythmic context. We developed methods to estimate oscillator properties (Experiment 1) and compared the estimates across tasks and individuals (Experiment 2). Preferred rates, estimated as the stimulus rates with peak performance, showed a harmonic relationship across measurements and were correlated with individuals' spontaneous motor tempo. Estimates from motor tasks were slower than those from the perceptual task, and the degree of slowing was consistent for each individual. Task performance decreased with trial-to-trial changes in stimulus rate, and responses on individual trials were biased toward the preceding trial's stimulus properties. Flexibility, quantified as an individual's ability to adapt to faster-than-previous rates, decreased with age. These findings show domain-specific rate preferences for the assumed oscillatory system underlying rhythm perception and production, and that this system loses its ability to flexibly adapt to changes in the external rhythmic context during aging.


Assuntos
Atenção , Percepção Auditiva , Humanos , Adulto , Atenção/fisiologia , Feminino , Masculino , Adulto Jovem , Idoso , Percepção Auditiva/fisiologia , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Estimulação Acústica , Adolescente
10.
Front Hum Neurosci ; 18: 1381232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841125

RESUMO

Successful music-making requires precise sensorimotor synchronization, both in individual (solo) and joint (ensemble) social settings. We investigated how individual practice synchronizing with a temporally regular melody (Solo conditions) influences subsequent synchronization between two partners (Joint conditions). Musically trained adults practiced producing a melody by tapping on a keypad; each tap generated the next tone in the melody. First, the pairs synchronized their melody productions with their partner in a baseline Joint synchronization task. Then each partner separately synchronized their melody with a computer-generated recording of the partner's melody in a Solo intervention condition that presented either Normal (temporally regular) auditory feedback or delayed feedback (by 30-70 ms) in occasional (25%) randomly placed tone positions. Then the pairs synchronized again with their partner in a Joint condition. Next, they performed the second Solo condition (normal or delayed auditory feedback) followed again by the Joint condition. Joint synchronization performance was modeled with a delay-coupled oscillator model to assess the coupling strength between partners. Absolute asynchronies in the Solo Intervention tasks were greater in the Delayed feedback condition than in the Normal feedback condition. Model estimates yielded larger coupling values between partners in Joint conditions that followed the Solo Normal feedback than the Solo Delayed feedback. Notably, the asynchronies were smaller in the Joint conditions than in the Solo conditions. These findings indicate that coupled interactions in settings of two or more performers can be improved by individual synchronization practice.

11.
Reprod Domest Anim ; 59(6): e14651, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923132

RESUMO

The efficiency of combining oestrous induction via a light program (16 h of light and 8 h of darkness for 60 days, ending on Day 0 - D0) with cloprostenol administration, followed by the male effect or not, was tested in acyclic Saanen goats during the non-breeding season (June/2019 to January/2020). Initially, all animals (males and females) were submitted to the described light program; 60 days after its ending (D60), the females were divided into two groups, with (G1; n = 67) or without (G2; n = 61) a male effect from D60 to D75 after the light program. At D75, both groups received two cloprostenol doses (120 µg; intramuscular) 7.5 days apart (D75 and D82.5). Artificial insemination was performed at a specific time according to the oestrous onset (approximately 68.4 ± 1.2 h between the second cloprostenol dose and IA). Ultrasound scans were performed at different intervals to evaluate follicular dynamics and confirm pregnancy. At the first cloprostenol dose (D75), the proportion of does with at least a corpus luteum (CL), which indicates resumed cyclicity, was greater in G1 than in G2 (85.2% vs. 48.8%; p < .05), although no difference was found at the second dose (p > .05). The adjusted pregnancy rates (number of pregnant goats/oestrous goats) differed between G1 and G2 (21.7% vs. 42.0%; p < .05). G1 also showed a higher frequency of functional CL (based on blood flow and morphology) compared to G2 (96.9% vs. 66.7%; p < .05) at D116. A male effect using photo-stimulated bucks after the first cloprostenol dose increased the number of does presenting CL after buck removal, and no impairment in the pregnancy rates of multiparous does was found.


Assuntos
Cloprostenol , Sincronização do Estro , Cabras , Inseminação Artificial , Estações do Ano , Animais , Cabras/fisiologia , Feminino , Masculino , Cloprostenol/farmacologia , Cloprostenol/administração & dosagem , Gravidez , Inseminação Artificial/veterinária , Prostaglandinas , Fotoperíodo , Reprodução/fisiologia , Reprodução/efeitos dos fármacos
12.
Entropy (Basel) ; 26(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38920484

RESUMO

The Belousov-Zhabotinsky (BZ) reaction has long been a paradigmatic system for studying chemical oscillations. Here, we experimentally studied the synchronization control within photochemically coupled star networks of BZ oscillators. Experiments were carried out in wells performed in soda-lime glass constructed using novel laser technologies. Utilizing the inherent oscillatory nature of the BZ reaction, we engineered a star network of oscillators interconnected through photochemical inhibitory coupling. Furthermore, the experimental setup presented here could be extrapolated to more complex network architectures with both excitatory and inhibitory couplings, contributing to the fundamental understanding of synchronization in complex systems.

13.
Entropy (Basel) ; 26(6)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38920533

RESUMO

Network topology plays a key role in determining the characteristics and dynamical behaviors of a network. But in practice, network topology is sometimes hidden or uncertain ahead of time because of network complexity. In this paper, a robust-synchronization-based topology observer (STO) is proposed and applied to solve the problem of identifying the topology of complex delayed networks (TICDNs). In comparison to the existing literature, the proposed STO does not require any prior knowledge about the range of topological parameters and does not have strict limits on topology type. Furthermore, the proposed STO is suitable not only for networks with fixed coupling strength, but also for networks with adaptive coupling strength. Finally, a few comparison examples for TICDNs are used to verify the feasibility and efficiency of the proposed STO, and the results show that the proposed STO outperforms the other methods.

14.
Rep Prog Phys ; 87(8)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38876094

RESUMO

Clock synchronization is critically important in positioning, navigation and timing systems. While its performance has been intensively studied in a wide range of disciplines, much less is known for the fundamental thermodynamics of clock synchronization‒what limits the precision and how to optimize the energy cost for clock synchronization. Here, we report the first experimental investigation of two stochastic autonomous clocks synchronization, unveiling the thermodynamic relation between the entropy cost and clock synchronization in an open cavity optomechanical system. Two interacting clocks are synchronized spontaneously owing to the disparate decay rates of hybrid modes by engineering the controllable cavity-mediated dissipative coupling. The measured dependence of the degree of synchronization on the overall entropy cost exhibits an unexpected non-monotonic characteristic, while the relation between the degree of synchronization and the entropy cost for the synchronization is monotonically decreasing. The investigation of transient dynamics of clock synchronization exposes a trade-off between energy and time consumption. Our results demonstrate the possibility of clock synchronization in an effective linear system, reveal the fundamental relation between clock synchronization and thermodynamics, and have a great potential for precision measurements, distributed quantum networks, and biological science.

15.
Brain Res Bull ; 215: 111017, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914295

RESUMO

Sleep staging plays an important role in the diagnosis and treatment of clinical sleep disorders. The sleep staging standard defines every 30 seconds as a sleep period, which may mean that there exist similar brain activity patterns during the same sleep period. Thus, in this work, we propose a novel time-related synchronization analysis framework named time-related multimodal sleep scoring model (TRMSC) to explore the potential time-related patterns of sleeping. In the proposed TRMSC, the time-related synchronization analysis is first conducted on the single channel electrophysiological signal, i.e., Electroencephalogram (EEG) and Electrooculogram (EOG), to explore the time-related patterns, and the spectral activation features are also extracted by spectrum analysis to obtain the multimodal features. With the extracted multimodal features, the feature fusion and selection strategy is utilized to obtain the optimal feature set and achieve robust sleep staging. To verify the effectiveness of the proposed TRMSC, sleep staging experiments were conducted on the Sleep-EDF dataset, and the experimental results indicate that the proposed TRMSC has achieved better performance than other existing strategies, which proves that the time-related synchronization features can make up for the shortcomings of traditional spectrum-based strategies and achieve a higher classification accuracy. The proposed TRMSC model may be helpful for portable sleep analyzers and provide a new analytical method for clinical sleeping research.

16.
bioRxiv ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38915653

RESUMO

Socially coordinated threat responses support the survival of animal groups. Given their distinct social roles, males and females must differ in such coordination. Here, we report such differences during the synchronization of auditory-conditioned freezing in mouse dyads. To study the interaction of emotional states with social cues underlying synchronization, we modulated emotional states with prior stress or modified the social cues by pairing unfamiliar or opposite-sex mice. In same-sex dyads, males exhibited more robust synchrony than females. Stress disrupted male synchrony in a prefrontal cortex-dependent manner but enhanced it in females. Unfamiliarity moderately reduced synchrony in males but not in females. In dyads with opposite-sex partners, fear synchrony was resilient to both stress and unfamiliarity. Decomposing the synchronization process in the same-sex dyads revealed sex-specific behavioral strategies correlated with synchrony magnitude: following partners' state transitions in males and retroacting synchrony-breaking actions in females. Those were altered by stress and unfamiliarity. The opposite-sex dyads exhibited no synchrony-correlated strategy. These findings reveal sex-specific adaptations of socio-emotional integration defining coordinated behavior and suggest that sex-recognition circuits confer resilience to stress and unfamiliarity in opposite-sex dyads.

17.
Neuroimage ; 297: 120700, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942103

RESUMO

People perform better collectively than individually, a phenomenon known as the collective benefit. To pursue the benefit, they may learn from previous behaviors, come to know whose initial opinion should be valued, and develop the inclination to take it as the collective one. Such learning may affect interpersonal brain communication. To test these hypotheses, this study recruited participant dyads to conduct a perceptual task on which they made individual decisions first and then the collective one. The enhanced interpersonal brain synchronization (IBS) between participants was explored when individual decisions were in disagreement vs. agreement. Computational modeling revealed that participant dyads developed the dyad inclination of taking the higher-able participants', not the lower-able ones' decisions as their collective ones. Brain analyses unveiled the enhanced IBS at frontopolar areas, premotor areas, supramarginal gyri, and right temporal-parietal junctions. The premotor IBS correlated negatively with dyad inclination and collective benefit in the absence of correction. The Granger causality analyses further supported the negative relation of dyad inclination with inter-brain communication. This study highlights that dyads learn to weigh individuals' decisions, resulting in dyad inclinations, and explores associated inter-brain communication, offering insights into the dynamics of collective decision-making.

18.
J Synchrotron Radiat ; 31(Pt 4): 821-828, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38900458

RESUMO

This study introduces a compact, portable femtosecond fibre laser system designed for synchronization with SPring-8 synchrotron X-ray pulses in a uniform filling mode. Unlike traditional titanium-sapphire mode-locked lasers, which are fixed installations, our system utilizes fibre laser technology to provide a practical alternative for time-resolved spectroscopy, striking a balance between usability, portability and cost-efficiency. Comprehensive evaluations, including pulse characterization, timing jitter and frequency stability tests revealed a centre wavelength of 1600 nm, a pulse energy of 4.5 nJ, a pulse duration of 35 fs with a timing jitter of less than 9 ps, confirming the suitability of the system for time-resolved spectroscopic studies. This development enhances the feasibility of experiments that combine synchrotron X-rays and laser pulses, offering significant scientific contributions by enabling more flexible and diverse research applications.

19.
J Am Pharm Assoc (2003) ; : 102145, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851585

RESUMO

BACKGROUND: An appointment-based medication synchronization (ABMS) is a service which aligns patients' chronic medications to a predetermined routine pickup date and includes a comprehensive medication review or other clinical appointment at the pharmacy. We compared healthcare utilization outcomes (outpatient, inpatient, emergency department visits, and pharmacy utilization) of Medicare beneficiaries enrolled in a med-sync program to beneficiaries not enrolled in such a program. METHODS: This retrospective cohort study included Medicare beneficiaries obtaining medications from pharmacies providing ABMS. All Medicare inpatient, outpatient, emergency, and pharmacy claims data from 2014 to 2016 obtained from the Research Data Assistance Center (ResDAC). These pharmacy claims were used to create medication-synchronized (med-sync) (n=13,193) and non-med-sync (n=156,987) cohorts. All patients were followed longitudinally for 12 months before and after a 2015 index/enrollment date. Baseline characteristics were utilized to create a logistic regression model for propensity score matching. A 1:1 greedy nearest neighbor matching algorithm was adapted for sequentially matching both cohorts. Difference-in-differences (DID) was used to compare mean changes in healthcare utilization outcomes (outpatient, inpatient, emergency department visits, and pharmacy utilization) between cohorts. RESULTS: After matching, 13,193 beneficiaries in each cohort were used for analysis. DID for mean of healthcare utilizations were significantly lower in the med-sync cohort compared to the non-med-sync cohort for outpatient visits (DID:0.012, p=0.0073) and pharmacy utilization (DID:0.013, p<0.0001). There was no significant DID for inpatient and emergency department visits between cohorts. CONCLUSION: Outpatient and pharmacy utilization changes were significantly lower in the med-sync cohort compared to the non-med-sync cohort in the 12-months after enrollment. Lower pharmacy utilization could be due to reducing duplicate prescriptions during synchronized refills or optimization of therapy during medication reviews if patients are enrolled in ABM med-sync.

20.
Front Netw Physiol ; 4: 1351815, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863734

RESUMO

Background: Abnormal neuronal synchrony is associated with several neurological disorders, including Parkinson's disease (PD), essential tremor, dystonia, and epilepsy. Coordinated reset (CR) stimulation was developed computationally to counteract abnormal neuronal synchrony. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites. Computational studies in plastic neural networks reported that CR stimulation drove the networks into an attractor of a stable desynchronized state by down-regulating synaptic connections, which led to long-lasting desynchronization effects that outlasted stimulation. Later, corresponding long-lasting desynchronization and therapeutic effects were found in animal models of PD and PD patients. To date, it is unclear how spatially dependent synaptic connections, as typically observed in the brain, shape CR-induced synaptic downregulation and long-lasting effects. Methods: We performed numerical simulations of networks of leaky integrate-and-fire neurons with spike-timing-dependent plasticity and spatially dependent synaptic connections to study and further improve acute and long-term responses to CR stimulation. Results: The characteristic length scale of synaptic connections relative to the distance between stimulation sites plays a key role in CR parameter adjustment. In networks with short synaptic length scales, a substantial synaptic downregulation can be achieved by selecting appropriate stimulus-related parameters, such as the stimulus amplitude and shape, regardless of the employed spatiotemporal pattern of stimulus deliveries. Complex stimulus shapes can induce local connectivity patterns in the vicinity of the stimulation sites. In contrast, in networks with longer synaptic length scales, the spatiotemporal sequence of stimulus deliveries is of major importance for synaptic downregulation. In particular, rapid shuffling of the stimulus sequence is advantageous for synaptic downregulation. Conclusion: Our results suggest that CR stimulation parameters can be adjusted to synaptic connectivity to further improve the long-lasting effects. Furthermore, shuffling of CR sequences is advantageous for long-lasting desynchronization effects. Our work provides important hypotheses on CR parameter selection for future preclinical and clinical studies.

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