Journal of neurophysiology最新文献

Transcutaneous spinal direct current stimulation (TSDCS) has the potential to modulate spinal circuits and induce functional changes in humans. Nevertheless, differences across studies on basic parameters used and obtained metrics represent a confounding factor. Computer simulations are instrumental in improving the application of the TSDCS technique. Their findings allow a better interpretation of the tissue conductivities heterogeneity. Emerging findings indicate the electric field is maximal in the segments located between the electrodes, and that factors such as the depth of the targeted area, and location of the electrodes on low conductive points, such as the spinous processes, may impact the electric field generated in the spinal cord, with consequences for thoracic versus lumbar or cervical applications. Recently, growing attention has been directed toward the importance of the TSDCS reference electrode's position and its influence on the current field properties at the targeted site. This review highlights the influence of dosage, polarity, and electrode position on the variety of TSDCS results in healthy and some clinical populations. Based on the available evidence, we suggest that although the current dosage appears to have a negligible effect, the variety of electrode montages and configurations of TSDCS can significantly impact the electric field distributions and potentially explain the conflicting results of experimental studies. Future human trials should systematically and thoughtfully evaluate the location of TSDCS electrodes based on the targeted neural structures.

The phase-dependent modulation pattern of the tibialis anterior (TA) flexion reflex was characterized during treadmill walking while transspinal stimulation was delivered at 15, 30, and 50 Hz above and below paresthesia in healthy participants. The flexion reflex was elicited following medial arch foot stimulation with a 30 ms (300 Hz) pulse train. During treadmill walking, the flexion reflex was evoked in the right leg every 3-5 steps, and stimuli were randomly dispersed across the step cycle that was divided into 16 equal bins. For each participant, condition and bin of the step cycle, the flexion reflex was measured as the area of the linear EMG envelope starting 20 ms after the end of the pulse train up to 200 ms and was normalized to the maximum locomotor TA EMG activity. The unconditioned flexion reflex was modulated in a phase-dependent manner. Transspinal stimulation, regardless frequency, or intensity produced pronounced flexion reflex depression during walking that coincided with an unchanged slope and intercept, computed from the linear relationship between the flexion reflex and background EMG activity. These findings suggest that transspinal stimulation above and below paresthesia intensities at 15, 30, and 50 Hz downregulates the flexion reflex. Based on our recently reported absent effects on the soleus H-reflex under similar conditions and our current findings we propose that transspinal stimulation downregulates flexion and not extension reflex pathways. More research is needed to delineate whether similar neuromodulation effects are present in flexion and extension reflexes after spinal cord injury in humans.NEW & NOTEWORTHY Transspinal stimulation over the thoracolumbar region above and below paresthesia intensities at 15, 30, and 50 Hz produces a generalized depression of the tibialis anterior flexion reflex during walking in healthy participants. This finding supports strong actions of transspinal stimulation on spinal neuronal networks engaged in walking. This finding may be helpful for recovery of walking after spinal cord injury in humans because suppression of exaggerated flexion reflexes enables smooth stance-to-swing transition and foot clearance.

For individuals with motor complete spinal cord injury (SCI), previous works have shown that spared motor neurons below the injury level can still be voluntarily controlled. In this study, we investigated the behavior of these neurons after SCI by analyzing neural and spatial properties of individual motor units using high-density surface electromyography (HDsEMG) and ultrasound imaging. The dataset for this study is based on motor unit data from our previous work (Oliveira et al. Brain 147: 3583-3595, 2024). Eight participants with chronic motor complete SCI and twelve uninjured controls attempted multiple hand movements, guided by a virtual hand, while we recorded forearm muscle activity. We analyzed the common synaptic input to motor neurons with a factorization method and found two dominant motor unit modes in both the SCI and control groups. Each mode was strongly correlated with the virtual hand's flexion or extension movements. The delay between flexion and extension movements and the motor unit modes was similar between groups, suggesting preserved common input to motor neurons after SCI. We classified motor units into task-modulated or nonmodulated (i.e., tonic or irregularly firing) based on their discharge patterns and phase difference with virtual hand kinematics and found a higher proportion of nonmodulated motor units in the SCI group. At the motor unit action potential level, we found larger motor unit territories after SCI. Finally, we observed distinct movements of paralyzed muscles with concurrent HDsEMG and ultrasound imaging, indicating the presence of highly functional motor units with distinct spared territories after SCI.NEW & NOTEWORTHY Here, we observed a similar pattern of motor unit activation during attempted hand movements in individuals with complete SCI, who cannot move their fingers, and in a control group, who performed the prescribed movements. Despite differences in individual motor unit behavior between these groups, such as a higher proportion of nonmodulated motor units in SCI, movement intention can still be decoded from paralyzed muscles.

Our purpose was to compare the influence of the spectral content of motor unit recordings on the calculation of electromechanical delay and on the prediction of force fluctuations from measures of the variability in discharge times and neural drive during steady isometric contractions with the first dorsal interosseus muscle. Participants (n = 42; 60 ± 13 yr) performed contractions at 5% and 20% MVC. After satisfying the inclusion criteria, high-density surface EMG recordings from a subset of 23 participants were decomposed into the discharge times of 530 motor units. The force and cumulative spike train (CST) signals were cross-correlated with a novel filtering approach to determine the electromechanical delay. Force and CST signals were bandpass filtered with three bandwidths (0.75-5 Hz, 0.75-2 Hz, and 2-5 Hz) to determine the influence of spectral content on the precision of the electromechanical delay measurement. Subsequently, the variability in the discharge times of motor units was quantified as the coefficient of variation for interspike interval (CVISI), and the variability in neural drive was represented as the standard deviation of the cumulative spike train (SDCST). The main findings were that all frequencies (0.75-5 Hz) were needed to determine the electromechanical delay and that the force fluctuations were best explained by measures of variability in both discharge times and neural drive (CVISI and SDCST) at 5% MVC force but only the variability in neural drive (SDCST) at 20% MVC force. These findings indicate that the source of the force fluctuations during the steady submaximal contractions with the hand muscle differed for the two target forces.NEW & NOTEWORTHY The fluctuations in force during steady submaximal contractions can be caused by either or both the variability in discharge times of individual motor units and in the neural drive. After careful alignment of the force and discharge times within an optimal bandwidth (0.75-5 Hz), the fluctuations in force at the lower target force were strongly correlated with both measures of variability, whereas those at the higher target force were best explained by the variability in neural drive.

Plans are formulated and refined throughout the period leading up to their execution, ensuring that the appropriate behaviors are enacted at the appropriate times. Although existing evidence suggests that memory circuits convey the passage of time through diverse neuronal responses, it remains unclear whether the neural circuits involved in planning exhibit analogous temporal dynamics. Using publicly available data, we analyzed how activity in the mouse frontal motor cortex evolves during motor planning. Individual neurons exhibited diverse ramping activity throughout a delay interval that preceded a planned movement. The collective activity of these neurons was useful for making temporal predictions that became increasingly precise as the movement time approached. This temporal diversity gave rise to a spectrum of encoding patterns, ranging from stable to dynamic representations of the upcoming movement. Our results indicate that ramping activity unfolds over multiple timescales during motor planning, suggesting a shared mechanism in the brain for processing temporal information related to both memories from the past and plans for the future. NEW & NOTEWORTHY Neuronal responses in the cortex are diverse, but the nature and functional consequences of this diversity remain ambiguous. We identified a specific pattern of temporal heterogeneity in the mouse frontal motor cortex, whereby the firing of different neurons ramps up at varying speeds before the execution of a movement. Our decoding analyses reveal that this heterogeneity in ramping dynamics enables precise and reliable encoding of movement plans and time across various timescales.

In 19 people probabilistic DTI tractography was used to visualize the topographic relationships between three white matter components of a fascicle, the supraventricular temporal bundle, that traverses above the temporal horn of the lateral ventricle: collothalamic auditory and visual projections to the amygdala via the posterior thalamus, and the amygdalofugal stria terminalis. This bundle constitutes a subcortical, 'low road' pathway that transmits threat signals to the amygdala, and that projects signals that bias orienting toward visual threat to the bed nucleus of the stria terminalis. The course of the visual streamline passes below the brachium of the superior colliculus through the position two thalamic nuclei that have been shown to both receive afferents from the superficial layers of the superior colliculus and to also project to the amygdala: the suprageniculate nucleus and the inferior pulvinar. The visual streamline passes laterally dorsal to the auditory streamline and both collothalamic streamlines then traverse together above the temporal horn of the lateral ventricle, dorsal to the stria terminalis, with the auditory streamline dorsal to visual streamline, and entering the lateral amygdala dorsal and medial to it. Individual differences in the degree of hemispheric asymmetry of the fractional anisotropy of the visual streamline, but not the auditory streamline, predicted trait anxiety: weaker left hemisphere connectivity relative to those in the right hemisphere, was associated with higher trait anxiety. There was no correlation between individual differences in the microstructure of either the stria terminalis or the ventral amygdalofugal pathway and trait anxiety.

The virtual movement of an augmented body, perceived as part of oneself, forms the basis of kinesthetic perception induced by visual stimulation (KINVIS). KINVIS is a visually induced virtual kinesthetic perception that clinically suppresses spasticity. The present study hypothesized that central neural network activity during KINVIS affects subcortical neural circuits. The present study aimed to elucidate whether reciprocal and presynaptic inhibition occurs during KINVIS. Seventeen healthy participants were recruited (mean age: 27.9 ± 3.6 yr), and their soleus Hoffmann-reflexes (H-reflexes) were recorded by peripheral nerve stimulation while perceiving the dorsiflexion kinesthetic illusion in the right-side foot (seated in a comfortable chair). Two control conditions were set to observe the same foot video without the kinesthetic illusion while focusing on the static foot image. Unconditioned H-reflex and two types of conditioned H-reflexes were measured: Ia (reciprocal inhibition) and D1 (presynaptic inhibition). Reciprocal Ia and D1 inhibition of the soleus muscle was significantly enhanced during the kinesthetic illusion compared with the condition without kinesthetic illusion (a post hoc analysis using the Bonferroni test: Ia inhibition, P = 0.002; D1 inhibition, P = 0.049). This study indicates that kinesthetic illusion elicits an inhibitory effect on the monosynaptic reflex loop of Ia afferents, potentially inhibiting the hyperexcitability of the stretch reflex. These findings demonstrate that brain activity associated with visually induced kinesthetic illusions acts on spinal inhibition circuits. These insights may be valuable in clinical rehabilitation practice, specifically for the treatment of spasticity.NEW & NOTEWORTHY Neural effects in visual-induced kinesthetic illusion expand into the spinal reflex. Kinesthetic illusion inhibits the monosynaptic reflex in an antagonistic muscle via reciprocal and presynaptic inhibition. Visually induced kinesthetic illusion is a suitable treatment for spasticity in patients with stroke.

Spreading depolarization (SD) temporarily shuts down neural processing in mammals and insects. Age is a critical factor for predicting the consequences of SD in humans. We investigated the effect of aging in an insect model of SD and explored the contribution of oxidative stress. Aging slowed the recovery of intact locusts from asphyxia. We monitored SD by recording the DC potential across the blood-brain barrier in response to bath application of the Na⁺/K⁺-ATPase inhibitor, ouabain. Ouabain induced changes to the DC potential that could be separated into two distinct components: a slow, permanent negative shift, like the negative ultraslow potential recorded in mammals and human patients, and rapid, reversible negative DC shifts (SD events). Aging had no effect on the slow shift but increased the duration of SD events. This was accompanied by a decrease in the rate of recovery of DC potential at the end of the SD event. An attempt to generate oxidative stress using rotenone was unsuccessful, but pretreatment with the antioxidant, N-acetylcysteine amide, had opposite effects to those of aging, reducing duration, and increasing rate of recovery, suggesting that it prevented oxidative damage occurring during the ouabain treatment. The antioxidant also reduced the rate of the slow negative shift. We propose that the aging locust nervous system is more vulnerable to stress due to a prior accumulation of oxidative damage. Our findings strengthen the notion that insects provide useful models for the investigation of cellular and molecular mechanisms underlying SD in mammals.NEW & NOTEWORTHY Anoxia and similar energetic crises trigger a shutdown of central neural processing in a process of spreading depolarization (SD) that is generally pathological in mammals and protective in insects. We show that older animals are slower to recover from SD in an insect model. Moreover, preventing oxidative stress with an antioxidant speeds recovery. These findings demonstrate the role of oxidative stress in contributing to the vulnerability of the aging insect central nervous system (CNS) in energetic emergencies.

Integration of autonomic and metabolic regulation, including hepatic function, is a critical role played by the brain's hypothalamic region. Specifically, the paraventricular nucleus of the hypothalamus (PVN) regulates autonomic functions related to metabolism, such as hepatic glucose production. Although insulin can act directly on hepatic tissue to inhibit hepatic glucose production, recent evidence implicates that central actions of insulin within PVN also regulate glucose metabolism. However, specific central circuits responsible for insulin signaling with relation to hepatic regulation are poorly understood. As a heterogeneous nucleus essential to controlling parasympathetic motor output with notable expression of insulin receptors, PVN is an appealing target for insulin-dependent modulation of parasympathetic activity. Here, we tested the hypothesis that insulin activates hepatic-related PVN (PVN^hepatic) neurons through a parasympathetic pathway. Using transsynaptic retrograde tracing, labeling within PVN was first identified 24 h after its expression in the dorsal motor nucleus of the vagus (DMV) and 72 h after hepatic injection. Critically, nearly all labeling in medial PVN was abolished after a left vagotomy, indicating that PVN^hepatic neurons in this region are part of a central circuit innervating parasympathetic motor neurons. Insulin also significantly increased the firing frequency of PVN^hepatic neurons in this subregion. Mechanistically, rapamycin pretreatment inhibited insulin-dependent activation of PVN^hepatic neurons. Therefore, central insulin signaling can activate a subset of PVN^hepatic neurons that are part of a unique parasympathetic network in control of hepatic function. Taken together, PVN^hepatic neurons related to parasympathetic output regulation could serve as a key central network in insulin's ability to control hepatic functions.NEW & NOTEWORTHY Increased peripheral insulin concentrations are known to decrease hepatic glucose production through both direct actions on hepatocytes and central autonomic networks. Despite this understanding, how (and in which brain regions) insulin exerts its action is still obscure. Here, we demonstrate that insulin activates parasympathetic hepatic-related PVN neurons (PVN^hepatic) and that this effect relies on mammalian target of rapamycin (mTOR) signaling, suggesting that insulin modulates hepatic function through autonomic pathways involving insulin receptor intracellular signaling cascades.