Journal of neurophysiology最新文献

Posterior root reflexes elicited by transcutaneous spinal stimulation (TSS) are useful for assessing spinal excitability and guiding neuromodulation interventions. Although various stimulation parameters have been extensively studied, the effect of pulse duration on reflex characteristics has not been thoroughly examined. This study systematically characterized posterior root reflexes across eight pulse durations ranging from 50 to 2,000 µs in 12 healthy participants using unipolar lumbosacral TSS (cathode over T11-12 processes, bilateral anode paraumbilically). In addition, in a subgroup of six participants, the repeatability of reflex characteristics over 2-3 mo was evaluated, and differences between the unipolar and bipolar configurations were examined. Recruitment curves in the major leg muscles reached similar plateau amplitudes across the pulse durations but shifted toward higher stimulation intensities with shorter pulses. The strength-duration curves for the motor threshold intensity were similar across muscles, with an average rheobase of 44.4 mA and a chronaxie of 362.9 µs. The strength-duration curves corresponding to 90% of the recruitment plateau revealed a 24.8 mA higher rheobase and only a 46.9 µs shorter chronaxie. Onset latencies of amplitude-matched reflexes increased 0.81 ms from 50 to 2,000 µs. Paired-pulse suppression demonstrated minimal dependency on pulse duration, although some muscle-specific variations were observed. The two ancillary experiments demonstrated good test-retest repeatability of the unipolar configuration and higher rheobase without significant differences in chronaxie with the bipolar configuration. We conclude that a wide range of pulse durations can produce posterior root reflexes when the stimulation intensity is properly adjusted. These findings offer a framework for selecting stimulation parameters for electrical neuromodulation.NEW & NOTEWORTHY The study demonstrates the impact of pulse duration on posterior root reflex characteristics across the dynamic range of the recruitment curve. It shows that strength-duration parameters-rheobase and chronaxie-are specific to the transcutaneous spinal stimulation settings and cannot be generalized from peripheral nerve H-reflex studies. The adequate reliability of the unipolar configuration is relevant for longitudinal studies, whereas the similarity between the unipolar and bipolar configurations indicates that they are complementary.

Pupil diameter, controlled by the autonomic nervous system (ANS), reflects numerous processes, from arousal to cognitive functions. In particular, the characteristics of the pupil at rest, its size and dynamics, reflect the tonic activity of the ANS. However, which factor can influence these pupillary characteristics at rest remains unclear. The pupil exhibits a physiological rhythmic oscillation, called hippus, which remains poorly characterized. Our aim was to better characterize the hippus by investigating how its parameters were influenced by different low- (illumination) and high-level (executive functioning) conditions. Pupil size variations of 30 adults (19-35 yr old) were recorded during five randomly appearing blocks. Although always requiring central fixation, the blocks varied according to gradients of illumination (11-lx, 19-lx, and 28-lx) and cognitive load (fixation, dot counting, and mental subtraction). Three main parameters were assessed: the median pupil diameter, the frequency, and amplitude of the hippus. Increasing illumination yielded smaller pupils and reduced hippus amplitude, while hippus frequency remained stable. In contrast, distinct effects were observed for the two high-level conditions. High cognitive load produced sustained pupil dilation and heightened hippus frequency, while intermediate counting showed minimal change except a decrease in hippus amplitude. Individual baseline pupil size was predictive of the amplitude of changes induced by the parameters. Our findings suggest that resting-state pupil oscillations are modulated differentially by low- and high-level influences, likely via integrative structures such as the locus coeruleus and superior colliculus, but also by biomechanical constraints.NEW & NOTEWORTHY We demonstrate, for the first time in a single within-subject protocol, how low-level (illumination) and high-level (cognitive load) factors differentially shape both baseline pupil size and the oscillatory hippus. Bright light drives tonic constriction and reduces hippus amplitude probably via iris biomechanics, while mental effort elicits dilation and increases hippus frequency through central arousal circuits. Individual resting-pupil profiles predict the amplitude of these responses.

In the Fmr1-knockout (KO) mouse model of fragile X syndrome (FXS), visual cortical slices exhibit enhanced persistent spiking following electrical stimulation in layer 5 (L5) when bathed with artificial cerebral spinal fluid (aCSF) emulating the ionic concentrations measured in vivo. This phenotype is of particular interest because it responds to several treatments that have been shown to correct a wide array of other disease phenotypes. However, the underlying mechanisms and physiological relevance of this hyperactivity phenotype are unknown in large part because of our incomplete understanding of the persistent spiking activity itself. In recordings from wild-type visual cortical slices, we find that extratelencephalic (ET) (but not intratelencephalic) L5 pyramidal neurons (PNs) are spontaneously active in physiological aCSF during pharmacological inhibition of ionotropic synaptic transmission. We show that this activity depends upon aCSF composition. Physiological divalent cation concentrations profoundly enhance the intrinsic excitability of ET L5 PNs in large part by altering the voltage dependence of the persistent sodium current (I_NaP). As a result, many ET PNs exhibit spontaneous, I_NaP-mediated activity. We show that the excitability and spontaneous activity of Fmr1-KO ET PNs are unchanged relative to WTs, indicating that the unstimulated Fmr1-KO L5 circuit is not spontaneously hyperactive in the absence of external input.NEW & NOTEWORTHY As extracellular divalent cation concentrations are reduced, neocortical slices become spontaneously active. Here, we show that these conditions enhance persistent sodium currents, driving intrinsically generated activity in a subclass of layer 5 neurons. This spontaneous activity is no different in Fmr1-knockout mice, however, pointing toward a crucial role for external input in eliciting a well-studied form of hyperactivity in Fmr1-knockout visual cortex.

Maturation of human brain structure has been well-studied, but developmental changes to brain physiology are not as well understood. One consistent finding is that the peak alpha rhythm frequency (PAF) increases throughout childhood. Another is that resting-state functional connectivity shifts from sensorimotor regions in children to association regions in adolescents, a reorganization along a hierarchy called the sensorimotor-to-association (S-A) axis. In mature brains, the S-A axis has been parcellated physiologically using the duration of persistent neural activity, known as the intrinsic neural timescale (INT), which increases along the hierarchy. Here, we studied the development of PAF and INT in a cohort of patients with epilepsy 3-33 yr of age undergoing intracranial electrocorticographic (ECoG) monitoring. Given the well-known developmental trajectory of PAF, and the ability to delineate hierarchy using INT, we hypothesized that changes to PAF and INT would correlate across development, but that their relationship may be influenced by hierarchy. Consequently, we predicted that age-dependent PAF increases would accompany INT decreases, and we tested whether their relationship varied between sensorimotor and association regions. We found that PAF increased significantly with age in both sensorimotor and association regions, whereas age-dependent INT decreases were only significant in association regions. Supporting this finding, we found a significant negative relationship between PAF and INT in association regions, but not sensorimotor regions. Together, our results provide further evidence that developmental divisions across the S-A axis manifest in the relationships between neurophysiological measures.NEW & NOTEWORTHY We report a novel developmental relationship between the human resting-state alpha rhythm frequency and the duration of intrinsic neural timescales. Using resting-state electrocorticography, we found that alpha frequency increased with age at either end of the sensorimotor-to-association cortical hierarchy, whereas intrinsic neural timescales only decreased with age in association regions. This negative correlation between alpha frequency and intrinsic timescale was only evident in association regions, further linking functional maturation and cortical hierarchy.

Patients suffering carbon monoxide (CO) poisoning exhibit elevations of ∼1-μm diameter blood-borne microparticles that murine studies have demonstrated to be responsible for a weeks-long cycle of neuroinflammation leading to functional neurological deficits. We hypothesized that an early event in the cycle is enhanced glymphatic flow to release brain-derived MPs, and that the adherence of circulating MPs to the central nervous system vasculature occurs via endothelial CD36 to cause neutrophil sequestration, which disrupts the blood-brain barrier. Results demonstrate that endothelial CD36 engagement of microparticles is required for pathological events, including neutrophil sequestration, leading to a 2.5 ± 0.6-fold increased vasculature leakage of 6 MDa dextran and induction of neuroinflammatory proteins. These changes increase glymphatic flow by 95 ± 26% based on magnetic resonance imaging and fluorescent tracer uptake, resulting in the release of brain-derived microparticles capable of activating neutrophils that complete a cycle of progressive neuroinflammation. The cyclic cascade of events, shown to persist for 3 wk, failed to occur in CD36 knock-out mice and those conditionally deficient in endothelial CD36 (CD36^flox/flox; Tie2-Cre+). We conclude that endothelial CD36 engagement of circulating microparticles precedes and is required for neutrophil adherence to perpetuate the neuroinflammatory cycle involving brain-derived and blood-borne microparticles.NEW & NOTEWORTHY CO-induced neuroinflammation requires endothelial CD36 engagement of circulating microparticles that trigger neutrophil vascular adherence, neuroinflammation, and a transient elevation of glymphatic flow, establishing a self-perpetuating neuroinflammatory cycle.

Long-range synchrony in the frog retina has been reported to be accompanied by oscillations. In this study, we found novel long-range synchronous firing without oscillatory activities. Spatially correlated visual stimuli were presented to the frog retina, after which spike responses from dimming detectors were analyzed to investigate the correlated spike activities and receptive fields (RFs). The results revealed precise synchronous firing from both adjacent cell pairs with overlapping RFs and cell pairs with distant RFs of up to 1,500 µm apart, even in the absence of oscillatory activities. Clear double-peaked cross correlograms were not detected. A considerable number of cell pairs exhibited RFs estimated from the synchronized spikes predominantly overlapped with those of one of the original cell pairs, suggesting that such synchronous firing can encode redundant spatial information. These results indicated the existence of a long-range neural substrate that generates precise synchrony among dimming detectors in response to spatially correlated stimuli. As the coincident spikes provide strong synaptic input to downstream neurons, synchronized spikes among dimming detectors might contribute to reliable signal transmission in the tectum, in which multiple retinal ganglion cells converge onto a single neuron.NEW & NOTEWORTHY In this study, we identified a novel form of long-range synchronous firing-occurring without oscillatory activities-among frog retinal ganglion cells known as dimming detectors. Spatially correlated visual stimuli evoked precise synchronous firing, even between cells with nonoverlapping receptive fields (RFs). RFs estimated from synchronized spikes predominantly overlapped with one cell's RF, suggesting redundant spatial coding. This synchronous firing might enhance reliable signal transmission from the retina to the tectum.

The purpose of our study was to compare motor unit modes derived from high-density surface electromyogram recordings from proximal and distal regions of the tibialis anterior muscle during submaximal isometric contractions. Motor unit activity was recorded with two grid electrodes attached to the skin over the muscle while participants performed isometric contractions to five targets that ranged from 5 to 60% of maximal torque. Factor analysis of the smoothed discharge rates yielded two distinct motor unit modes-defined as subsets of motor units in which the modulation of discharge rate was correlated presumably due to shared synaptic input. Motor units were classified into two modes based on the proximity of each correlation value to two independent centroids. The analysis indicated that most proximal motor units were associated with mode 1, whereas distal motor units were more associated with mode 2. Low cross-correlation values between the two modes for each participant (range: 0.11-0.28) indicated that the modes were independent. Moreover, median Z scores of the pooled coherence for the discharge rates derived from pairs of motor units were less between the two modes than within either mode. The percentage of motor units associated with mode 1 increased with target torque in most participants but decreased in the others, indicating regional differences in the modulation of discharge rate across individuals. These findings suggest that motor units in the proximal and distal regions of tibialis anterior can exhibit differential modulation of discharge rate during submaximal isometric contractions.NEW & NOTEWORTHY The findings of this study suggest that the force produced by the tibialis anterior muscle during submaximal isometric contractions is controlled by two anatomically distinct motor unit modes. Moreover, factor and coherence analyses indicated that motor units in proximal and distal regions of the muscle received independent shared synaptic inputs. These results challenge the assumption of a uniform neural drive to the tibialis anterior muscle during submaximal isometric contractions.

The vagus nerve (cranial nerve X) originates in the brainstem, and extends through the neck, thorax, and abdomen, linking the brain to key organs of the gastrointestinal and cardiopulmonary systems. The motor division of the vagus nerve originates from two brainstem nuclei-the nucleus ambiguous (NAmb) and the dorsal motor nucleus of the vagus (DMV)-that modulate the motor and secretion control of the gastrointestinal (GI) tract. Sensory inputs from the GI tract are transmitted by vagal afferents to the nucleus tractus solitarius (NTS), which modulates DMV activity to coordinate processes like peristalsis, gastric secretion, and pancreatic functions. This complex network of motor and sensory pathways is vital for regulating GI function and maintaining homeostasis. Stress disrupts the excitatory-inhibitory balance within the DMV, leading to alterations in gastrointestinal motility and secretion. This imbalance plays a significant role in pathological conditions such as irritable bowel syndrome and functional dyspepsia. Furthermore, a crucial regulatory pathway from the substantia nigra pars compacta (SNpc) to the DMV modulates GI activity and is implicated in the etiology of Parkinson's disease, where GI symptoms are often prodromal to motor dysfunction. In this context, vagal nerve stimulation emerges as a promising therapeutic approach, enhancing gut health and cognitive function through neuroprotection and inflammation reduction. These findings underscore the vital gut-brain connection in the treatment of neurological disorders.

This article discusses the significance of a recent study by Kwaśniak et al. (Sci Rep 15: 36337, 2025). This study assessed neural activation during the generation of motor imagery in aphantasics and control participants. The results of this study are placed in the context of the broader aphantasia literature and the importance of these results within the field of cognitive and motor neuroscience is emphasized.

Simple four-neuron computational models comprising bilateral pairs of excitatory dIN and inhibitory cIN neurons were used to test several hypotheses concerning the role of electrogenic sodium pumps in shaping swimming CPG output in Xenopus tadpoles. The initial model had no sodium pumps and generated continuous swim-like rhythmic activity. In real tadpoles, activity-dependent "dynamic" sodium pumps are proposed to mediate the postswim ultraslow afterhyperpolarization (usAHP) apparent in most cINs that reduces subsequent swim episode durations, producing a form of short-term motor memory (STMM). Dynamic pumps were therefore incorporated into model cINs, which then generated a usAHP causing swimming episodes to self-terminate, and when interswim intervals were varied, the model also replicated STMM. In real tadpoles, no usAHP is normally apparent in dINs, but one can be revealed by pharmacologically blocking the hyperpolarization-activated current, I_h, which is exclusively expressed in dINs. Dynamic pumps and HCN channels mediating I_h were therefore added to the model dINs. If HCN conductance was locked at its resting level, the dINs now showed a substantial pump-generated usAHP, but this was almost completely cancelled when HCN conductance was allowed to respond normally. Complete cancellation could be achieved by including a speculative cAMP-mediated modulation of the HCN activation kinetics. The models thus confirm the plausibility of published hypotheses regarding the generation of the usAHP in cINs, its apparent absence in dINs due to masking by I_h, and its role in mediating STMM. They also suggest the involvement of the usAHP in swim termination and possible regulation by cyclic nucleotides.NEW & NOTEWORTHY The tadpole locomotor network, an important model system in motor control, has been extensively modeled. Dynamic sodium pumps can generate a slow afterhyperpolarization (usAHP) that contributes to swimming. Here, we present novel computer models that incorporate these pumps and replicate both the usAHP and spinal motor memory. We also show that the usAHP can be masked by HCN channels, validating the conclusions of physiological experiments and suggesting new mechanisms of network function.