Excitation Patterns Research Articles

In general, optimizing chromaticity and transverse feedback parameters is important in suppressing beam instabilities for stable operation in high-intensity proton machines. Meanwhile, space charge effects impact the intrabunch motion of the proton bunch within a large chromaticity region in the machines, such as the main ring (MR) in the Japan Proton Accelerator Research Complex (J-PARC). To address this issue, the decoherence and recoherence of the transverse motion of the particles comprising the proton bunch are investigated. The analysis reveals that the space charge effects have a significant influence on the recoherence period through the chromaticity. Nevertheless, the relationship between the maximum frequency in the bunch and the chromaticity is not affected by the space charge effects. These findings are demonstrated with particle tracking simulations, including the direct and indirect space charge effects, and the impedance source of the J-PARC MR. Furthermore, we illustrate the influence of the indirect space charge effect on particle motion by examining the excitation patterns of radial and head-tail modes.

The Electrical Capacitance Tomography (ECT) imaging pipeline relies on accurate estimation of electric field distributions to compute electrode capacitances and reconstruct permittivity maps. Traditional ECT forward model methods based on the Finite Element Method (FEM) offer high accuracy but are computationally intensive, limiting their use in real-time applications. In this proof-of-concept study, we investigate the use of Graph Convolutional Networks (GCNs) for direct, one-step prediction of electric field distributions associated with a circular ECT sensor numerical model. The network is trained on FEM-simulated data and outputs of full 2D electric field maps for all excitation patterns. To evaluate physical fidelity, we compute capacitance matrices using both GCN-predicted and FEM-based fields. Our results show strong agreement in both direct field prediction and derived quantities, demonstrating the feasibility of replacing traditional solvers with fast, learned approximators. This approach has significant implications for further real-time ECT imaging and control applications.

This study examines how auditory spectral representations in the peripheral auditory system explain changes in vowel production under noisy conditions, especially when lower formants (F1 and F2) are masked. Ten adult male Japanese speakers produced sustained vowels /a/ and /i/ under quiet and noisy conditions involving three noise types (broadband, low-pass, and high-pass) at 75 and 85 dB. We analyzed vocal intensity and the amplitudes and frequencies of the F1 and F2. Auditory spectral representations, simulated using a loudness model, were used to estimate excitation patterns in the auditory periphery. Most noise conditions significantly increased vocal intensity and the amplitude of both formants. F1 frequency consistently shifted upward under high-intensity broadband noise, while F2 shifts depended on vowel and noise type, shifting upward for /a/ and downward for /i/. Some patterns could not be explained by power spectra alone. Instead, they were better accounted for by frequency-specific masking effects, reflected in overlapping excitation patterns in the auditory spectral representation. These overlaps indicated reduced self-audibility in specific frequency bands, triggering compensatory adjustments. The findings highlight how auditory masking influences speech production, supporting a perceptually grounded model of auditory-motor control in noisy environments.

Voltage-gated sodium (Nav) channels initiate and propagate action potentials in many excitable cells. Upon repetitive activation, the fraction of Nav channels available for excitation gradually decreases on a timescale ranging from seconds to minutes, a phenomenon known as slow inactivation. This process is crucial for regulating cellular excitability and firing patterns. Slow inactivation is proposed to result from the collapse of the selectivity filter pore coupled with the opening of the primary helix bundle crossing gate. However, the conformational changes underlying slow inactivation and the molecular coupling between the selectivity filter and primary gate remain unclear. In this study, we investigated the conformational dynamics of the selectivity filter in prokaryotic NavAb channels reconstituted into liposomes using single-molecule FRET (smFRET). Our smFRET data revealed the conformational transitions in the NavAb selectivity filter pore among three distinct states, with activating voltages enriching the high-FRET conformations, potentially associated with slow inactivation. Using electrophysiological and crystallographic methods, we further identified the L176 residue in the selectivity filter P1 helix as a critical coupler between the primary and slow inactivation gates. We showed that L176 mutations with side chains of larger sizes significantly facilitated the slow inactivation of the NavAb channel, and the L176F mutation forced the opening mutant carrying the C-terminal deletion to be crystallized at the closed state. Consistently, our smFRET results revealed that C-terminal deletion markedly attenuated the high FRET conformation of the selectivity filter, which was restored by the L176F mutation. Moreover, using the classical Nav open-pore blocker lidocaine, we showed that it also depleted the high FRET conformation of the NavAb selectivity filter in a dose-dependent manner. The L176F mutation, again, markedly reversed the conformational shifts caused by lidocaine, an effect similar to it on the opening mutant carrying the C-terminal deletion. Our studies consistently suggested that slow inactivation in the NavAb channel is underlined by the collapse of the selectivity filter pore, represented by the high FRET conformation uncovered by our smFRET measurements, while the L176 residue at the P1 helix of the selectivity filter and T206 at the pore lining helix couple the conformational changes of the slow inactivation gate at selectivity filter and the primary gate at the helix bundle crossing.

BackgroundFibroblast growth factor 2 (FGF2) has been implicated in modulating mood and addiction-related behaviors (Elsayed et al Biol Psychiatry 72:258, 2012). Previous studies have reported both anxiolytic and antidepressant-like effects of FGF2 as well as its potential pro-addictive effects (Even-Chen et al J Neurosci 37:8742, 2017). Given the critical role of central noradrenergic neurons in regulating mood, stress response, and arousal, it is plausible that FGF2 influences these behaviors via modulation of noradrenergic neuronal activity in the locus coeruleus (LC). However, the effects of FGF2 on the firing patterns of LC noradrenergic neurons remain poorly understood.Aims & ObjectivesThis study aimed to investigate the effect of recombinant FGF2 on the excitability and firing patterns of noradrenergic neurons in the LC of male and female rats, with a focus on burst firing activity.MethodAdult male and female Wistar rats were randomly divided into two groups. The first group received subcutaneous (s.c.) injection of FGF2 (80 μg/kg), and the second group received vehicle. One-hour post-injection, rats were anesthetized with chloral hydrate (0.4 g/kg, intraperitoneally) and placed in a stereotaxic frame. The electrode was lowered into the LC. Noradrenergic neurons were identified based on their characteristic firing patterns and action potential waveforms (Even-Chen et al J Neurosci 39:7947, 2019). Spontaneous firing activity was recorded for at least 3 minutes per neuron. The firing rate, burst frequency, and percent of spikes within bursts were analyzed for sex- and treatment-related differences.ResultsFGF2 significantly influenced the activity of noradrenergic neurons in the LC. The mean firing rate and burst frequency of LC neurons showed significant sex-related differences (F[1,147]=11.33, p<0.001 and F[1,128]=6.11, p=0.02, respectively), with males exhibiting higher values than females. Additionally, a significant interaction between sex and FGF2 treatment was observed for the percent of spikes within bursts (F1,128=3.98, p=0.048). Post-hoc analysis indicated that the firing rate was higher in males compared to females in both vehicle-treated (p=0.04) and FGF2-treated groups (p=0.007). Notably, sex-related differences in burst frequency (p=0.02) and percent of spikes within bursts (p=0.01) were evident only in the FGF2-treated rats. Moreover, FGF2 increased the percent of spikes within bursts in males by 130% compared to vehicle-treated rats (p=0.03), whereas no such effect was observed in females.Discussion & ConclusionsOur findings demonstrate that FGF2 enhances the burst firing activity of LC noradrenergic neurons, with pronounced sex differences in its effects. The ability of FGF2 to increase the percent of spikes within bursts in males suggests that it may selectively potentiate noradrenergic transmission in a sex-dependent manner. These results provide new insights into the role of FGF2 in modulating the central noradrenergic system and its potential implications for mood and arousal regulation.This work was supported by the grants APVV-20-0202, APVV-22-0061, VEGA-2/0057/22, and VEGA-2/0045/24.

Understanding the vibrational mode-specific dynamics of chemical reactions is crucial for unraveling the fundamental mechanisms that govern reactivity and product formation. In this study, we investigate the Cl + CH3CN reaction using quasi-classical trajectory simulations on a previously developed, high-quality, full-dimensional potential energy surface. By selectively exciting individual vibrational modes of the CH3CN reactant, we systematically analyze their influence on reaction probabilities and cross sections and, in the case of the major H-abstraction channel, on scattering and attack angle distributions, as well as product energy partitioning across a range of collision energies. Furthermore, a vibrational mode-specific product analysis, combined with energy-based Gaussian binning, was conducted to examine how initial mode excitation influences product state distributions. Our results reveal that excitation of specific reactant vibrational modes can enhance the H-abstraction probability without altering the overall reaction mechanism. A significant portion of the initial vibrational energy is transferred to the internal energy of the products, while the collision energy primarily contributes to their translational energy. The CH2CN product exhibits well-defined, mode-specific vibrational excitation patterns, reflecting distinct energy redistribution pathways during the reaction. These findings provide deeper insight into the role of vibrational energy in promoting or altering chemical reaction pathways in a polyatomic system.

Abstract The self-exciting spatio-temporal point process model is a fundamental tool for studying recurrent events in fields such as economics, criminology, and seismology. Existing models often assume that the productivity parameter, which measures the rate of triggered events, is constant in space and time. This assumption is often unrealistic, as it may not capture the complexity of some real-world phenomena. In this paper, we propose a new self-exciting model that relaxes this assumption by allowing the productivity parameter to vary smoothly in both space and time. Through simulation experiments, we demonstrate that our model can effectively recover the underlying pattern of excitation. Furthermore, we apply the proposed framework to a crime dataset, showing its ability to identify spatial and temporal heterogeneity in event dynamics. This approach offers a more realistic method for modeling spatio-temporal patterns, with significant potential for the development of surveillance and prevention tools in a range of applications.

Does artificial intelligence feedback result in different kinematic and muscle excitation patterns compared to physiotherapist feedback during lower-limb rehabilitation exercises?

Approaches to map cortical excitability beyond the primary motor cortex - Perspectives from cognitive neuroscience, multimodal imaging and clinical applications.

At high fundamental frequencies (fos), wide harmonic spacing can obscure typical formant cues. This study investigates the role of static spectral cues in maintaining vowel identity under such conditions. We resynthesized steady-state versions of eight German vowels (/i, y, e, ø, ɛ, a, o, u/) across fos ranging from 220 to 880 Hz from previously identifiable spoken vowels, preserving their gross spectral shapes. Twenty native German speakers participated in a two-alternative forced-choice identification task. Results showed that identification accuracy declined at higher fos, especially for vowels with less distinctive spectral features, sometimes approaching chance levels. However, vowels with more distinctive static spectral properties, particularly the point vowels /i/, /a/, and /u/, often remained identifiable above chance even at the highest fos. Auditory excitation patterns indicated that listeners rely on perceptual anchors at the boundaries of the vowel space, utilizing gross static spectral properties to maintain vowel contrasts when harmonic spacing undersamples the vocal tract transfer function. These findings suggest that the auditory system adapts to challenging acoustic conditions by relying on internal representations of vowel categories and static spectral cues, highlighting their importance in preserving vowel identity at high fos.

The synthesis and photophysical properties of highly substituted symmetrical difluoro‐boron‐triaza‐anthracene (BTAA) 5a–g and nonsymmetrical difluoro‐boron‐triaza‐cyclopentanaphthalene 8a–h (BTCPN) derivatives are reported. Herein, the 2‐pyridone was used as a platform to render these highly substituted structures. The BTAA and BTCPN derivatives were efficiently obtained in five steps and characterized by different spectroscopy methods and X‐ray data. An experimental analysis of the substituent effect on the photophysical properties of 5a–g and 8a–h was performed. The leading absorption bands of 5a–g and 8a–h are observed at ca. 348 nm, and the emission bands at ca. 536 nm. From series 5a–g and 8a–h, the compounds 5c and 8c showed the highest fluorescence quantum yield obtained in CH2Cl2 (φ = 58 and 76%, respectively). The large quantum yield of 5c and 8c is related to a small HOMO‐LUMO gap, analyzed by cam‐B3LYP/6‐311++g**/6‐311+g*. A bifurcation of the excitation pattern improves the quantum yield 8a compared to 5a. The large quantum yield of 8a is explained by two probable transitions involving the HOMO‐LUMO and HOMO‐LUMO + 1 excitation processes.

CLCN3 and CLCN4 encode the endosomal 2Cl-/H+ exchangers ClC-3 and ClC-4, which are highly expressed within the central nervous system, including hippocampal formation. Pathogenic variants recently found in these genes have given rise to the rare CLCN3- and CLCN4-neurodevelopmental conditions, characterised by a range of neurological and neuropsychiatric complications, such as global developmental delay, intellectual disability as a core feature, seizures, behavioural issues, and brain abnormalities. The mechanisms by which ClC-3 and ClC-4 regulate neuronal function and viability, as well as the molecular pathways affected in CLCN3- and CLCN4-related neurodevelopmental conditions, remain unknown. In neurodegenerative diseases, neuronal dendrites undergo pathological changes often associated with aberrant electrical activity. To investigate how ClC-3 or ClC-4 deficit alters neuronal excitability and morphology, we combined patch-clamp recordings in acute hippocampal slice preparations with simultaneous intracellular biocytin filling. We analysed the functional and structural properties of Clcn3-/- and Clcn4-/- neurons. Two firing patterns are found in the hippocampus's Cornu Ammonis 2 (CA2) region: regular and burst firing. At post-natal day 13 (P13), 62% of the assessed CA2 wild-type neurons showed a rhythmic bursting behaviour; this was reduced to 19% in Clcn4-/- and completely absent in the Clcn3-/- condition. Changes in the firing patterns were accompanied by a depolarising shift in the action potential threshold and an increase in the afterhyperpolarizing phase of the action potentials. Blockade of Kv7/KCNQ, and to a lesser extent Kv1, but not BK, SK or Kv2 channels, recapitulates the wild-type firing pattern phenotype in the Clcn3-/- condition. Moreover, we detected abnormalities in the complexity of the dendritic arborisation. Branching and lengths of apical and basal domains were significantly reduced in the Clcn3-/- and moderately altered in the Clcn4-/- neurons. At P3, we found 25% of bursting neurons in Clcn3-/- with no significant morphological abnormalities in the dendritic arborisation compared to the wild-type, suggesting that functional defects precede structural changes in Cl-/H+ exchangers-deficient neurons. Similarly, dentate granule cells exhibited defective action potential properties and reduced burst-firing activity, which was substantially, but not fully rescued by Kv7/KCNQ blockage. We conclude that Cl-/H+ exchangers regulate neurons' electrical excitability and firing patterns primarily by fine-tuning Kv7/KCNQ channel density, and that functional defects might contribute to alterations in dendritic morphology. Our findings provide new insights into the underlying molecular mechanisms of Cl-/H+ exchangers in neurons and pave the way toward potential therapeutic interventions for CLCN3- and CLCN4-related patients associated with disruption of Cl-/H+ exchange function.

The stochastic fluctuation characteristics of wind speed can significantly affect the control performance of train suspension systems. To enhance the running quality of trains in non-stationary wind fields, this paper proposes a semi-active control method for trains based on fuzzy rules of non-stationary wind fields. Firstly, a dynamic model of the train and suspension system was established based on the CRH2 (China Railway High-Speed 2) high-speed train and magnetorheological dampers. Then, using frequency–time transformation technology, the non-stationary wind load excitation and train response patterns under 36 common operating conditions were calculated. Finally, by analyzing the response patterns of the train under different operating conditions, a comprehensive control rule table for the semi-active suspension system of the train under non-stationary wind fields was established, and a fuzzy controller suitable for non-stationary wind fields was designed. To verify the effectiveness of the proposed method, the running smoothness of the train was analyzed using a train-semi-active suspension system co-simulation model based on real wind speed data from the Lanzhou–Xinjiang railway line. The results demonstrate that the proposed method significantly improves the running quality of the train. Specifically, when the wind speed reaches 20 m/s and the train speed reaches 200 km/h, the lateral Sperling index is increased by 46.4% compared to the optimal standard index, and the vertical Sperling index is increased by 71.6% compared to the optimal standard index.

The ways in which age affects neuromuscular control in response to walking-related fatigue are poorly understood. Better understanding of the consequences of walking-related fatigue can inform the development of strategies to improve independent mobility for older adults. In this study, we measured leg muscle excitations and net joint moments in younger and older adults during a 30-min walking trial. Twelve leg muscles were monitored, and wavelet transformation and principal component analyses quantified the effects of age and time on muscle excitation patterns. Perceived exertion increased in both age groups, with higher terminal values in older adults. Over the course of prolonged walking, mean EMG frequency and amplitude decreased while EMG intensities in the slower frequency ranges increased for soleus, lateral gastrocnemius, tibialis anterior, peroneus longus, and gluteus maximus muscles. For soleus muscle, a time-dependent decrease in mean frequency was observed only for older adults. We observed a distal-to-proximal redistribution of net joint moments during prolonged walking independent of age; however, older adults walked with greater peak hip joint moments than younger adults. Our results suggest that shank muscles may exhibit higher fatigability during prolonged walking, precipitating an increased demand on proximal leg muscles to power walking. Walking in older adults is often characterized by an increased reliance on proximal leg muscles, which has in turn been implicated in their higher metabolic cost of transport. Accordingly, our collective findings point to neuromuscular changes during prolonged walking that may cause older adults to be more susceptible to walking-related fatigue than younger adults.

Excitability is a fundamental property of cortical networks, shaping their responses to input. Here, we use ionic direct current (iDC) to modulate excitability with sub-10-ms temporal resolution and submillimeter spatial precision across the cortical surface, greatly surpassing the capabilities of pharmacological tools. In anesthetized rats, we recorded laminar neural responses in the S1HL cortex to spontaneous delta oscillations and to foot stimulation with and without iDC delivered to the cortical surface. Cathodic iDC suppressed, and anodic iDC enhanced, evoked responses across recording sites. iDC shifted the spatiotemporal excitability pattern in a graded manner, paralleling the effects of weaker or stronger foot stimuli. A computational model reproduced these effects and implicated dendritic summation at the axon initial segment (AIS) as a key mechanism for bidirectional modulation. This approach enables precise, causal manipulation of cortical responsiveness in vivo and offers a platform for dissecting functional circuits and developing targeted neurotherapeutic interventions.

ABSTRACTPhosphorus (P)–doped graphitic carbon nitride (g‐C3N4) represents a significant advancement in nonlinear optical (NLO) materials, where subtle atomic modifications induce notable changes in electronic behavior. In this study, we conduct a comprehensive quantum‐chemical and wavefunction‐based investigation into the electronic and NLO properties of both pristine and P‐doped g‐C3N4, under static and dynamic regimes. Using advanced real‐space function analyses, we reveal complex patterns of electronic excitation and charge redistribution, highlighting P‐doping's pivotal role in enhancing van der Waals attractions and exchange‐repulsion forces, which are essential for the material's binding interactions. The modulation of molecular (hyper)polarizabilities is systematically explored through sophisticated tools such as unit sphere representation and second‐order NLO spectra. Our findings show that P‐doping significantly enhances polarization anisotropy. Notably, the second‐order hyperpolarizability exhibits pronounced optical anisotropy, particularly in the xy‐plane, with a remarkable dispersion effect at 589 nm (γyyyy = 3.55 × 1010 a.u.), demonstrating unprecedented control over optical properties. The selected S2 and S4 structures exhibit strong octupolar behavior, with the octupolar molecular tensor contributing up to 80% of the NLO response. This study not only positions P‐doped g‐C3N4 at the forefront of high‐performance NLO material design but also paves the way for further exploration of heteroatom‐engineered carbon‐based nanostructures. These materials offer versatile platforms for advanced photonic and optoelectronic devices. Future directions could delve into the synergistic integration of P‐doped g‐C3N4 within hybrid architectures, broadening its potential for tunable NLO systems in fields such as quantum optics, telecommunications, and molecular sensing.

SUMMARYThe capacity of temporal interference (TI) stimulation to target deep brain regions without affecting nearby surface electrodes remains uncertain. Using artifact-free optical recording, we compare excitation patterns and thresholds in hippocampal neurons stimulated by “pure” and amplitude-modulated sine waves, representing TI waveforms near electrodes and at the target, respectively. We show that pure 2- and 20-kHz sine waves induce repetitive firing at rates that increase up to 60–90 Hz with stronger electric fields. Beyond this limit, action potentials merge into sustained depolarization, resulting in an excitation block. Modulating the sine waves at 20 Hz aligns firing with amplitude “beats” and prevents the excitation block but does not lower excitation thresholds. Thus, off-target TI effects appear unavoidable, though the patterns of neuronal excitation and downstream effects may differ from those at the target. We further analyze membrane charging and relaxation kinetics at nanoscale resolution and confirm an excitation mechanism independent of envelope extraction.

Cues associated with food, such as fast-food advertising, can provoke food cravings and may lead to unhealthy overeating. Environmental enrichment (EE) that enhances cognitive and physical stimulation can reduce cue-evoked sucrose seeking in mice and recruitment of sucrose cue-reactive neurons or ‘neuronal ensembles’ in the prelimbic cortex (PL), which regulates appetitive behaviors. Hence, EE provides us with a behavioral model and neuronal targets to identify ‘anti-craving’ relevant mechanisms. Here, we investigated in the PL how EE modulated neuronal excitability and activity patterns in cue-reactive neuronal populations. Chemogenetic inhibition of cue-reactive neurons in PL blocked cue-evoked sucrose seeking, thereby confirming the function of these neurons in sucrose cue memory. EE boosted the baseline excitability of ‘originally’, or before EE exposure, cue-reactive, excitatory pyramidal cells in PL. Furthermore, their sucrose cue-specificity was lost – resulting in their persistent activation and non-cue selective activation or ‘excitatory overdrive’. Furthermore, EE reduced recruitment of cue-reactive, inhibitory interneurons reflecting ‘inhibitory underdrive’. Taken together, impaired neuronal food cue processing due to simultaneous prefrontal cortical excitatory ‘overdrive’ and inhibitory ‘underdrive’ likely underlies EE’s anti-craving action, thereby serving as potential neurophysiological targets to develop novel medications that help control food cravings.

Single-molecule Tracking and Kinetic Analysis in Living Cells and Multicellular Organisms.

This study presents a computational model for simulating excitation propagation in the human heart using a Monodomain reaction-diffusion framework coupled with the Aliev-Panfilov model for the ionic reaction term. The objective is to address the Forward Problem in cardiac electrophysiology by modeling how electrical activation initiated at the conduction system propagates through the myocardium. Cellular and tissue-level dynamics are integrated using diffusion tensor imaging (DTI)-derived anisotropy and conduction network structures. Two conduction system models are evaluated, one based on trabecular muscle anatomy and another using diffusion volume (DV) metrics. Numerical simulations demonstrate activation isochrones comparable to experimental data from Durrer et al., highlighting the model's validity in capturing realistic ventricular excitation patterns. Visualization was achieved using OpenGL-based C/C++ simulations.