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.

In the core of a stroke, cell death occurs within minutes. In the penumbra, activity quickly drops, but cells typically remain viable for several hours. Improving neuronal survival in the penumbra is crucial for enhancing recovery in patients with stroke. Earlier work showed that mild activation may improve recovery, but the mechanisms are unclear. Brain-derived neurotrophic factor (BDNF) is well recognized for its neuroprotective functions via activation of tyrosine receptor kinase B (TrkB) receptors, and its release is activity-dependent. This study explored the role of BDNF/TrkB signaling in neuronal survival under hypoxic conditions, using cultures of dissociated cortical rat neurons. When exposed to hypoxia, activity quickly drops and cells become apoptotic after ∼12 h, similar to observations in the ischemic penumbra. Inhibition of the TrkB receptor in healthy, normoxic cultures led to a fivefold increase in apoptosis, confirming the importance of BDNF/TrkB signaling for cell viability in these preparations. The addition of BDNF to hypoxic cultures significantly improved neuronal survival, comparable with the effects of mild activation. These findings suggest that the beneficial effect of mild stimulation to prevent apoptosis in hypoxic cultures is mediated by BDNF/TrkB signaling, offering insights for potential therapeutic strategies aimed at promoting neuronal recovery after a stroke.NEW & NOTEWORTHY Low activity in the ischemic penumbra has been suggested as a critical factor leading to apoptosis. BDNF excretion is activity-dependent and has been shown to be neuroprotective. Blockade of TrkB receptors induced apoptosis in cultured neurons, comparable with the effects of hypoxia. BDNF administration was effective in mitigating hypoxia-induced apoptosis, suggesting that the beneficial effect of mild activation to prevent apoptosis in hypoxic cultures is mediated by BDNF-TrkB signaling.

Visual cross-modal plasticity after deafness describes when the sensory cortex compensates for auditory deprivation by increasing sensitivity to visual information. Cross-modal plasticity is evident in humans and animal models with deafness and is linked to improved visual perception, but it is unclear whether this occurs for mild, partial hearing loss. Here, we investigated cross-modal plasticity in adults with mixed levels of high-frequency hearing loss, but normal mid- and low-frequency hearing sensitivity, and whether this plasticity was associated with visual short-term memory recall. A total of 25 participants (aged 18-78) completed a modified Sternberg task with text-based words. Participants viewed a five-word sentence presented word-by-word during an encoding period and held these words in short-term memory during a retention period. After, they reported whether a target word probe was present in the encoding period. Multichannel electroencephalogram recorded visual cortical activity throughout. Results showed separate effects of high-frequency hearing and age on visual cortical responses. Visual N1 amplitudes were larger with worse sensitivity, and P2 latencies were longer. In contrast, age was associated with shorter P2 latencies. Source analysis found that the N1 amplitude increased with worse high-frequency hearing sensitivity in the right auditory cortex, but no effects were found in the visual cortex. Hearing sensitivity and visual encoding activity did not correlate with behavioral performance or neural oscillations during the retention period. Results suggest that even a mild decline of high-frequency hearing sensitivity is associated with increased visual activation of the right auditory cortex during an active visual processing task, consistent with cross-modal plasticity.NEW & NOTEWORTHY By recording the electroencephalogram and analyzing visual cortical potentials, we provide evidence for enhanced visual cortical sensitivity and recruitment of the auditory cortex during visual text perception in individuals with worse high-frequency hearing sensitivity. These individuals otherwise had normal middle- and lower-frequency hearing sensitivity, suggesting that visual cross-modal plasticity is initiated in early stages of hearing loss.

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.