Journal of neurophysiology最新文献

Neuronal firing patterning in the dentate gyrus of patients with epilepsy remains unknown at the microcircuit level. Advancements in high-density CMOS-based microelectrode arrays can be harnessed to study network activity with unprecedented spatial and temporal resolution. We use novel computational methods with high-density electrophysiology recordings to spatially map network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy. Two slices from the dentate gyrus exhibited synchronous bursting activity in the presence of low magnesium media with kainic acid, representative of seizure-like behavior. We bridged microscale circuit dynamics with alterations in theta oscillations at the network scale. Future studies may apply this approach to spatially elucidate functional networks and their possible role in seizures.NEW & NOTEWORTHY We apply high-density CMOS-based microelectrode arrays to excised patient brain slices, mapping the communication patterns of hundreds of neurons at unprecedented resolution. We developed novel computational techniques to spatially map neuronal dynamics. In patient slices, our findings suggest that recurrent feedback localized within the dentate gyrus of the hippocampus is linked to a previously unreported phenomenon of theta propagations. This bridges microscale circuit dynamics with alterations in theta oscillations.

Whether the auditory nervous system can extract and use speech information carried in the extended high-frequency (EHF; >8 kHz) range is an unresolved question in auditory neuroscience. Although EHF sensitivity is increasingly recognized as important for speech perception, it is unclear whether EHF hearing is directly or indirectly involved in real-world listening. This study examined brainstem neural encoding of EHF speech components and the relationship between EHF hearing sensitivity and both neural and perceptual speech processing. Envelope following responses (EFRs) to broadband and high-pass filtered (>4 kHz and >8 kHz) speech stimuli, along with digits-in-noise speech recognition thresholds under various masking conditions (broadband, <2 kHz, <4 kHz, <8 kHz), were measured in 47 normal-hearing adults. Our findings suggest that the auditory brainstem can phase-lock to temporal speech features carried in the EHF region (f₀ and f₀ modulation). Furthermore, participants with poorer EHF sensitivity showed weaker EFR f₀ amplitudes for both broadband and >4 kHz speech stimuli, as well as overall elevated speech recognition thresholds. EHF thresholds predicted both speech neural encoding strength and speech-in-noise performance, particularly under low-pass masking conditions. These results demonstrate that speech information carried in the EHF range weakly encodes important cues for speech perception, such as voice f₀ and f₀ modulation. Furthermore, poorer EHF hearing is associated with degraded neural encoding and perception of signals with dominant energy in the standard frequency range (<8 kHz).NEW & NOTEWORTHY This study provides the first evidence that the auditory nervous system can extract important temporal speech features (f₀ and f₀ modulation) from the extended high-frequency (EHF) region. Individuals with EHF loss exhibit weaker neural encoding of broadband and high-frequency speech stimuli, suggesting EHF deficits broadly affect neural transduction. These results advance understanding of EHF contributions to speech processing and demonstrate that EHF hearing sensitivity is linked to neural transduction and perception of broadband speech signals.

A 39-yr-old female with potassium-aggravated myotonia due to p.Q1633E in SCN4A experienced painful muscle stiffness triggered by exercise, potassium-rich fruits, and cold exposure, which progressed into a rigid state. Needle electromyography (EMG) during muscle stiffness showed synchronous, rhythmic, and regular activities starting at ∼60 Hz and ∼6 mV. A 37-yr-old male with myotonia permanens due to a splicing-affecting indel variant in intron 21 of SCN4A experienced cold-induced myotonia. EMG recordings during muscle stiffness showed similar synchronous, rhythmic, and regular activities starting at ∼80 Hz and 6.5 mV. In both patients, the frequencies and amplitudes were gradually decreased with relief of muscle stiffness. In either patient, single motor unit potentials by spontaneous activity were not explicitly recognized. In both patients, the activities produced a characteristic sound which, while similar in pitch to the "dive bomber" sound of classical myotonia, lacked its typical waxing and waning quality. The activities were similar to the Piper rhythm that was originally reported in fatigued normal muscle. Visual inspection of EMG activities in the literature revealed that similar Piper rhythm-like EMG activities were presented in Satoyoshi disease, myotonia permanens, paramyotonia congenita, and a rare form of nondystrophic myotonia. In Satoyoshi disease and fatigued normal skeletal muscle, the activities during muscle stiffness were less than 60 Hz, whereas in sodium channelopathies, they started at 60 Hz or higher, which may be a hallmark of hyperexcitability of the muscle membrane in sodium channelopathies.NEW & NOTEWORTHY In two patients with sodium channel myotonia representing potassium-aggravated myotonia and myotonia permanens, needle EMG showed Piper rhythm-like activities during muscle stiffness. Inspection of EMG recordings in the literature revealed similar Piper rhythm-like EMG activities in Satoyoshi disease, myotonia permanens, paramyotonia congenita, and a rare form of nondystrophic myotonia. Piper rhythm-like EMG activities starting at 60 Hz or higher, synchronizing with muscle stiffness, may be a hallmark of hyperexcitability of muscle membrane in sodium channelopathies.

Humans rely on well-calibrated internal models of physical laws, such as gravity, to guide efficient manual actions. In this study, we investigated whether such gravitational expectations are altered in virtual reality (VR) and how this might influence the execution and adaptation of goal-directed pointing movements. We compared pointing movements in physical and virtual environments, focusing on initial acceleration as an index of feedforward control. To capture trial-by-trial adaptation and the influence of prior beliefs on pointing movements, we modeled this data using the generalized hierarchical Gaussian filter, a Bayesian computational model of learning under uncertainty. Initial hand acceleration was found to be slightly lower in the virtual environment than in the physical environment, but no condition-related difference was found in variability of acceleration. Model-estimated gravity beliefs were found to be similar between virtual and physical environments, but belief certainty was observed to decline across trials in the virtual condition, suggesting an accumulation of uncertainty over time. In summary, gravity priors remained stable in VR, guiding action similarly to physical environments, but the sensory uncertainty of VR eroded the precision of these priors over time.NEW & NOTEWORTHY This study demonstrates that humans' sensorimotor priors about gravity remain stable when performing vertical pointing movements in virtual environments, despite accumulating sensory uncertainty over time. Using kinematic measures and a Bayesian computational model, we show that core predictive control transfers from real-world to immersive contexts but confidence in predictions declines with prolonged virtual reality (VR) exposure. These findings advance understanding of how predictive motor control adapts to VR, with implications for training, rehabilitation, and human-computer interaction.

Several neuroimaging modalities used in the study of posttraumatic stress disorder (PTSD) have documented various alterations in brain structure, function, and neurocircuitry relative to controls. Studies using magnetoencephalography (MEG), which provides direct evaluation of synaptic activity, have identified anomalies in neural communication prominently involving temporal areas. Here, we shift the focus from global neural interactions to evaluate moment-to-moment change in resting-state local synaptic activity, which we refer to as MEG turnover (MEGT) in 495 US veterans. Specifically, we compared MEGT in veterans with PTSD (n = 184) and healthy control veterans (n = 311), controlling for sex and age. The findings revealed that PTSD was associated with significantly higher turnover of the MEG signal in bilateral inferior frontal/anterior temporal cortical areas, right hemispheric parietal and occipital areas, and left cerebellum, whereas it was associated with significantly reduced MEG turnover in other areas, including primarily left hemispheric temporal and occipital areas and central sulcus. The PTSD-associated anomalies in local synaptic activity are presumably due to dysregulation of neurotransmitters that influence neural communication and synaptic plasticity, the effects of which may contribute to deficits in information processing that are characteristic of PTSD.NEW & NOTEWORTHY Local synaptic activity can be measured by evaluating the moment-to-moment change, or turnover, of the magnetoencephalography (MEG) signal. Here we found that posttraumatic stress disorder (PTSD) was associated with highly significant differences in resting-state MEG turnover (MEGT) compared with controls, the direction of which varied across the cortex. Since synaptic activity depends on neurotransmitters, these findings are consistent with models implicating neurotransmitter dysregulation in PTSD.

This study investigates how the properties of neural temporal modulation transfer functions (TMTFs) derived from envelope following responses (EFRs) to amplitude-modulated sounds relate to the hypothetical tuning of individual neurons in the midbrain. We followed a joint modeling and empirical approach. We measured EFRs for young adults with normal hearing (n = 15) using rectangular amplitude-modulated (RAM) tones with modulation frequencies varying between 70 and 160 Hz, to target the most sensitive region of brainstem/midbrain neurons. These empirical data portrayed a large variability across individuals, both in terms of TMTF shapes and gains; at the individual level, most individuals exhibited TMTFs band-pass or low-pass in shape, but at the group level, there was no significant trend. We also conducted simulations using computational models of the auditory periphery and midbrain to examine how simulated, EFR-derived TMTFs vary depending on hypothesized models of inferior-colliculus (IC) neurons, their parameters, and distributions. When considering a population of band-pass-tuned IC cells with varying best modulation frequencies, simulations suggest that the magnitude of the TMTF, rather than its shape, might actually better reflect a change in tuning. These experimental and simulation results are discussed in relation to previous works, along with additional simulations showing that the type of stimulus envelope (sinusoidal vs. rectangular modulation) or subtle threshold variations among individuals with normal hearing have only a limited impact on these trends. From these results, we derive several considerations for the interpretation of EEG-based TMTFs and the potential information they provide regarding auditory midbrain tuning.NEW & NOTEWORTHY What do EEG-derived temporal modulation transfer functions (TMTFs) tell us about human auditory midbrain tuning? We found substantial individual variability in both the shapes and gains of empirically derived TMTFs. Computational model simulations suggest that the TMTF's magnitude, rather than its shape, might better reflect underlying neural tuning changes. These results provide new perspectives for modeling individual differences and for developing more sensitive clinical tests of subcortical temporal processing.

Locusts exhibit remarkable phenotypic plasticity, changing their appearance and behavior from solitary to gregarious when population density increases. These changes include morphological differences in the size and shape of brain regions, but little is known about plasticity within individual neurons and alterations in behavior not directly related to aggregation or swarming. We investigated looming escape behavior and the properties of a well-studied collision-detection neuron in gregarious and solitarious animals of three closely related species, the desert locust (Schistocerca gregaria), the Central American locust (S. piceifrons), and the American bird grasshopper (S. americana). For this neuron, the lobula giant movement detector (LGMD), we examined dendritic morphology, membrane properties, gene expression, and looming responses. This is the first study done on three different species of grasshoppers to observe the effects of phenotypic plasticity on the jump escape behavior, physiology, and transcriptomics of these animals. Unexpectedly, there were few differences in these properties between the two phases, except for behavior. For the three species, gregarious animals jumped more than solitarious animals, but no significant differences were found between the two phases of animals in the electrophysiological and transcriptomic studies of the LGMD. Our results suggest that phase change impacts mainly the motor system and that the physiological properties of motor neurons need to be characterized to fully understand the variation in jump escape behavior across phases.NEW & NOTEWORTHY Some grasshopper species swarm, called locusts. We compared jump escape behavior between gregarious and solitarious grasshoppers and locusts, as well as LGMD responses to looming stimuli, and analyzed potential physiological differences in this sensory neuron. This study provides insights into the effects of phase change on the visual system of locusts and grasshoppers as it relates to looming-evoked jump escape behavior. In this context, our results suggest that phenotypic plasticity mainly impacts the motor system.

Increasing the visual gain of the force output during constant isometric contractions reduces the amplitude of force fluctuations in young adults. However, these findings are based on metrics of force variability, such as the standard deviation (SDF) or coefficient of variation (CVF) in force, ignoring force smoothness. Here, we examined the effects of increasing the gain of visual feedback on force variability and force smoothness during constant isometric contractions. Fourteen young adults (20.1 ± 1.4 yr; 10 F) performed ankle dorsiflexion at 10% maximum for 40 s with low-gain (LG; 0.1°) and high-gain (HG; 5.0°) visual feedback. We quantified force variability (SDF and CVF), force smoothness [dF/dt; first time-derivative of force (YANK)], and power spectral density of the force and tibialis anterior (TA) muscle activity [electromyogram (EMG)]. Participants exhibited lower SDF and CVF (lower variability), but greater YANK (lower smoothness) during the HG condition. The reduction in SDF with HG was associated with a reduction in the power of 0-0.5 Hz force oscillations (R² = 0.82) and a reduction in the power of 1.5-2 Hz TA EMG oscillations (R² = 0.29). The increase in YANK with HG was associated with an increase in the power of 7-8 Hz force oscillations (R² = 0.82) and an increase in the power of 35-60 Hz TA EMG oscillations (R² = 0.25). These findings suggest that force variability and force smoothness are distinct concepts, reflecting separate physiological processes influenced by visual gain manipulation.NEW & NOTEWORTHY These findings suggest that force variability and force smoothness are distinct motor control features influenced differently by visual gain manipulation. Although variability reflects fluctuations in force amplitude, smoothness captures the consistency of force transitions. The dissociation between these measures indicates that they are governed by separate physiological mechanisms. This distinction has important implications for understanding sensorimotor integration and designing targeted interventions to improve motor performance in tasks requiring precise and sustained force control.

Naloxone is the prototypical opioid receptor antagonist, whereas naloxone-methiodide, a quaternary naloxone analog, is widely used as a peripherally restricted antagonist based on the assumption that it does not cross the blood-brain barrier. This assumption has been central to arguments that peripheral opioid receptors contribute to fentanyl-induced respiratory depression. However, mass spectrometry studies show that although naloxone-methiodide has very limited permeability, it is detectable in brain tissue at an ∼1:50 concentration ratio compared with naloxone. Even such small amounts may be sufficient to act on brain receptors, raising the possibility of central involvement. To test this hypothesis, we used oxygen sensors coupled with amperometry in freely moving rats to examine the roles of central versus peripheral opioid receptors in fentanyl-induced brain hypoxia. We compared naloxone with naloxone-methiodide on oxygen responses in the brain and subcutaneous space following intravenous fentanyl administration (30 µg/kg). Naloxone-methiodide at a dose of 2.0 mg/kg (but not 0.2 mg/kg) blocked fentanyl-induced hypoxia. Naloxone-methiodide's effect was weaker and shorter than that produced by 0.2 mg/kg naloxone. In addition, naloxone at doses 50- and 250-times lower (0.04 and 0.008 mg/kg), but not 1,000-times lower (0.002 mg/kg), also blocked fentanyl-induced hypoxia, mimicking the effect of 2.0 mg/kg naloxone-methiodide. These findings suggest that naloxone-methiodide is not a strictly peripheral antagonist. At moderate to high doses, naloxone-methiodide's ability to reverse fentanyl-induced hypoxia may be partially mediated by the drug's action on central opioid receptors.NEW & NOTEWORTHY It is widely believed that opioids cause brain hypoxia through direct central nervous system action. This was challenged using naloxone-methiodide, which is believed to not cross the blood-brain barrier. However, mass-spectrometry data show limited brain entry, sufficient to block fentanyl-induced hypoxia. Our data reveal that naloxone is effective at 40 and 8 μg/kg doses, whereas naloxone-methiodide is not selective for peripheral opioid receptors. Its effects at higher doses arise mainly from central opioid receptor blockade.