Neurophysiological Recordings Research Articles

A large-scale optogenetic neurophysiology platform for improving accessibility in NHP behavioral experiments.

Optogenetics has been a powerful scientific tool for two decades, yet its integration with non-human primate (NHP) electrophysiology has been limited due to several technical challenges. These include a lack of electrode arrays capable of supporting large-scale and long-term optical access, inaccessible viral vector delivery methods for transfection of large regions of cortex, a paucity of hardware designed for large-scale patterned cortical illumination, and inflexible designs for multi-modal experimentation. To address these gaps, we introduce a highly accessible platform integrating optogenetics and electrophysiology for behavioral and neural modulation with neurophysiological recording in NHPs. We employed this platform in two rhesus macaques and showcased its capability of optogenetically disrupting reaches, while simultaneously monitoring ongoing electrocorticography activity underlying the stimulation-induced behavioral changes. The platform exhibits long-term stability and functionality, thereby facilitating large-scale electrophysiology, optical imaging, and optogenetics over months, which is crucial for translationally relevant multi-modal studies of neurological and neuropsychiatric disorders.

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5–14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

Distinctive Neurophysiological Signatures of Analgesia after Inflammatory Pain in the ACC of Freely Moving Mice.

Preclinical assessments of pain have often relied upon behavioral measurements and anesthetized neurophysiological recordings. Current technologies enabling large-scale neural recordings, however, have the potential to unveil quantifiable pain signals in conscious animals for preclinical studies. Although pain processing is distributed across many brain regions, the anterior cingulate cortex (ACC) is of particular interest in isolating these signals given its suggested role in the affective ("unpleasant") component of pain. Here, we explored the utility of the ACC toward preclinical pain research using head-mounted miniaturized microscopes to record calcium transients in freely moving male mice expressing genetically encoded calcium indicator 6f (GCaMP6f) under the Thy1 promoter. We verified the expression of GCaMP6f in excitatory neurons and found no intrinsic behavioral differences in this model. Using a multimodal stimulation paradigm across naive, pain, and analgesic conditions, we found that while ACC population activity roughly scaled with stimulus intensity, single-cell representations were highly flexible. We found only low-magnitude increases in population activity after complete Freund's adjuvant (CFA) and insufficient evidence for the existence of a robust nociceptive ensemble in the ACC. However, we found a temporal sharpening of response durations and generalized increases in pairwise neural correlations in the presence of the mechanistically distinct analgesics gabapentin or ibuprofen after (but not before) CFA-induced inflammatory pain. This increase was not explainable by changes in locomotion alone. Taken together, these results highlight challenges in isolating distinct pain signals among flexible representations in the ACC but suggest a neurophysiological hallmark of analgesia after pain that generalizes to at least two analgesics.

Gold nanosheet modified electrode with reduced impedance for electrophysiological recordings

In neurophysiological recording, reducing electrode impedance is crucial for enhancing the signal-to-noise ratio and achieving the desired spatial resolution. This study presents an approach to improve the performance of Au/Cr/glass electrodes by incorporating synthesized gold nanosheets without the need for additional adhesive material. We characterized the performance of the modified electrodes using electrochemical impedance spectroscopy and equivalent circuit analysis. Our findings showed an 81% reduction in mean impedance for the modified electrode, which was 0.85 kΩ at 1 kHz, compared to the unmodified electrode at 4.5 kΩ, an improvement attributed to the higher effective surface area of the modified electrode. Additionally, Scanning electron microscopy observations of PC12 cells cultured on the modified electrodes indicated favorable cell elongation and interaction with the rough surface. Stability studies indicated acceptable performance of the modified electrodes in solution environments. These results suggest that surface modification of electrodes with gold nanosheets could be a promising strategy for enhancing neural interface applications.

High-Density, Conformable Conducting Polymer-Based Implantable Neural Probes for the Developing Brain.

Neurologic and neuropsychiatric disorders substantially impact the pediatric population, but there is a lack of dedicated devices for monitoring the developing brain in animal models, leading to gaps in mechanistic understanding of how brain functions emerge and their disruption in disease states. Due to the small size, fragility, and high water content of immature neural tissue, as well as the absence of a hardened skull to mechanically support rigid devices, conventional neural interface devices are poorly suited to acquire brain signals without inducing damage. Here, the authors design conformable, implantable, conducting polymer-based probes (NeuroShanks) for precise targeting in the developing mouse brain without the need for skull-attached, rigid mechanical support structures. These probes enable the acquisition of high spatiotemporal resolution neurophysiologic activity from superficial and deep brain regions across unanesthetized behavioral states without causing tissue disruption or device failure. Once implanted, probes are mechanically stable and permit precise, stable signal monitoring at the level of the local field potential and individual action potentials. These results support the translational potential of such devices for clinically indicated neurophysiologic recording in pediatric patients. Additionally, the role of organic bioelectronics as an enabling technology to address questions in developmental neuroscience is revealed.

A personalized earbud for non-invasive long-term EEG monitoring

Objective. The primary objective of this study was to evaluate the reliability, comfort, and performance of a custom-fit, non-invasive long-term electrophysiologic headphone, known as Aware Hearable, for the ambulatory recording of brain activities. These recordings play a crucial role in diagnosing neurological disorders such as epilepsy and in studying neural dynamics during daily activities. Approach. The study uses commercial manufacturing processes common to the hearing aid industry, such as 3D scanning, computer-aided design modeling, and 3D printing. These processes enable the creation of the Aware Hearable with a personalized, custom-fit, thereby ensuring complete and consistent contact with the inner surfaces of the ear for high-quality data recordings. Additionally, the study employs a machine learning data analysis approach to validate the recordings produced by Aware Hearable, by comparing them to the gold standard intracranial electroencephalography recordings in epilepsy patients. Main results. The results indicate the potential of Aware Hearable to expedite the diagnosis of epilepsy by enabling extended periods of ambulatory recording. Significance. This offers significant reductions in burden to patients and their families. Furthermore, the device’s utility may extend to a broader spectrum, making it suitable for other applications involving neurophysiological recordings in real-world settings.

Gait-related beta-gamma phase amplitude coupling in the subthalamic nucleus of parkinsonian patients

Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson’s disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN). We analyzed bilateral STN local field potentials (LFPs) in eight subjects with PD chronically implanted with deep brain stimulation electrodes during upright quiet standing and unperturbed walking. Phase-amplitude coupling (PAC) was computed using the Kullback-Liebler method, based on the modulation index. Neurophysiological recordings were correlated with clinical and kinematic measurements and individual molecular brain imaging studies ([123I]FP-CIT and single-photon emission computed tomography). We showed a dopamine-related increase in subthalamic beta-gamma PAC from standing to walking. Patients with poor PAC modulation and low PAC during walking spent significantly more time in the stance and double support phase of the gait cycle. Our results provide new insights into the subthalamic contribution to human gait and suggest cross-frequency coupling as a gateway mechanism to convey patient-specific information of motor control for human locomotion.

"Real-Time Neuromonitoring" Increases the Safety and Non-Invasiveness and Shortens the Duration of Idiopathic Scoliosis Surgery.

Introduction: A practical solution to the incidental unreliability of intraoperative neuromonitoring (IONM) may be the simultaneous neurophysiological recording and control of the surgical field through a camera (the concept of "Real-time" IONM). During "Real-time" IONM, the surgeon is immediately warned about the possibility of damage to the neural structures during, but not after, standard idiopathic scoliosis (IS) corrective surgery procedures (the concept of "Surgeon-neurophysiologist" interactive, verbal IONM). This study aimed to compare the advantages, utilities, reliabilities, and time consumption of the two IONM scenarios. Methods: Studies were performed in two similar groups of patients undergoing surgery primarily due to Lenke 2 idiopathic scoliosis (N = 120), when both IONM approaches were applied. Neurophysiological evaluations of the spinal transmission were performed pre- (T0), intra- (before (T1) and after (T2) surgery), and postoperatively (T3), as well as once in healthy volunteers (control, N = 60). Non-invasive and innovative recordings of the motor evoked potentials (MEPs) bilaterally from the peroneal (PER) nerve and tibialis anterior (TA) muscle were performed with surface electrodes as a result of transcranial magnetic stimulation (TMS) or electrical stimulation (TES) at T0-T3. Results: In both groups, the MEP amplitudes and latencies recorded from the PER nerve were approximately 67% lower and 3.1 ms shorter than those recorded from the TA muscle. The MEP recording parameters differed similarly at T0-T3 compared to the control group. In all patients, the MEP parameters induced by TMS (T0) and TES (T1) did not differ. The MEP amplitude parameters recorded from the TA and PER at T1 and T2 indicated a bilateral improvement in the neural spinal conduction due to the surgical intervention. The TMS-induced MEP amplitude at T3 further increased bilaterally. In both IONM groups, an average 51.8 BIS level of anesthesia did not affect the variability in the MEP amplitude, especially in the PER recordings when the applied TES strength was 98.2 mA. The number of fluctuations in the MEP parameters was closely related to the number of warnings from the neurophysiologist during the transpedicular screw implantation, corrective rod implantation, and distraction, derotation, and compression procedures, and it was higher in the "Surgeon-neurophysiologist" IONM group. The average duration of surgery was shorter by approximately one hour in the "Real-time" IONM group. The number of two-way communications between the surgeon and the neurophysiologist and vice versa in the "Real-time" IONM group decreased by approximately half. Conclusions: This study proves the superiority of using "Real-time" IONM over the standard "Surgeon-neurophysiologist" IONM procedure in increasing the safety and non-invasiveness, shortening the time, and lowering the costs of the surgical treatment of IS patients. The modifications of the MEP nerve-conduction-recording technology with surface electrodes from nerves enable precise and reliable information on the pediatric patient's neurological condition at every stage of the applied surgical procedures, even under conditions of slight fluctuations in anesthesia.

An adaptive h-refinement method for the boundary element fast multipole method for quasi-static electromagnetic modeling

Objective. In our recent work pertinent to modeling of brain stimulation and neurophysiological recordings, substantial modeling errors in the computed electric field and potential have sometimes been observed for standard multi-compartment head models. The goal of this study is to quantify those errors and, further, eliminate them through an adaptive mesh refinement (AMR) algorithm. The study concentrates on transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), and electroencephalography (EEG) forward problems. Approach. We propose, describe, and systematically investigate an AMR method using the boundary element method with fast multipole acceleration (BEM-FMM) as the base numerical solver. The goal is to efficiently allocate additional unknowns to critical areas of the model, where they will best improve solution accuracy. The implemented AMR method’s accuracy improvement is measured on head models constructed from 16 Human Connectome Project subjects under problem classes of TES, TMS, and EEG. Errors are computed between three solutions: an initial non-adaptive solution, a solution found after applying AMR with a conservative refinement rate, and a ‘silver-standard’ solution found by subsequent 4:1 global refinement of the adaptively-refined model. Main results. Excellent agreement is shown between the adaptively-refined and silver-standard solutions for standard head models. AMR is found to be vital for accurate modeling of TES and EEG forward problems for standard models: an increase of less than 25% (on average) in number of mesh elements for these problems, efficiently allocated by AMR, exposes electric field/potential errors exceeding 60% (on average) in the solution for the unrefined models. Significance. This error has especially important implications for TES dosing prediction—where the stimulation strength plays a central role—and for EEG lead fields. Though the specific form of the AMR method described here is implemented for the BEM-FMM, we expect that AMR is applicable and even required for accurate electromagnetic simulations by other numerical modeling packages as well.

The discrepancy in triggered electromyography responses between fatty filum and normal filum terminale

BackgroundFunctional role of filum terminale (FT) was not well studied though it contains structure basis for nerve impulse conduction. We aimed to explore the possible functions of the FT from the perspective of triggered electromyography (EMG) during surgery.MethodsWe retrospectively reviewed intraoperative neurophysiological monitoring data from pediatric patients who underwent intradural surgeries at the lumbar level in Shanghai Children’s. Hospital from January 2018 to March 2023. Altogether 168 cases with complete intraoperative neurophysiological recordings of the FT were selected for further analysis. Triggered EMG recordings of the filum originated from two main types of surgeries: selective dorsal rhizotomy (SDR) and fatty filum transection.Results96 cases underwent SDR and 72 cases underwent fatty filum transection. Electrical stimulation of the FT with fatty infiltration did not elicit electromyographic activity in the monitored muscles with the maximum stimulus intensity of 4.0 mA, while the average threshold for FT with normal appearance was 0.68 mA, and 89 out of 91 FT could elicit electromyographic responses in monitored channels. The threshold ratio of filum to motor nerve roots at the same surgical segment was significantly higher in patients with fatty filum, and a cut-off point of 21.03 yielded an area under curve of 0.943, with 100% sensitivity and 85.71% specificity.ConclusionFilum with normal appearance can elicit electromyographic activity in the lower limbs/anal sphincter similar to the performance of the cauda equina nerve roots. The threshold of fatty filum is different from that of normal appearing FT. Triggered EMG plays an important role in untethering surgeries.

Pediatric Intraoperative Neurophysiologic Mapping and Monitoring in Brain Surgery.

Similar to adults, children undergoing brain surgery can significantly benefit from intraoperative neurophysiologic mapping and monitoring. Although young brains present the advantage of increased plasticity, during procedures in close proximity to eloquent regions, the risk of irreversible neurological compromise remains and can be lowered further by these techniques. More so, pathologies specific to the pediatric population, such as neurodevelopmental lesions, often result in medically refractory epilepsy. Thus, their successful surgical treatment also relies on accurate demarcation and resection of the epileptogenic zone, processes in which intraoperative electrocorticography is often employed. However, stemming from the development and maturation of the central and peripheral nervous systems as the child grows, intraoperative neurophysiologic testing in this population poses methodologic and interpretative challenges even to experienced clinical neurophysiologists. For example, it is difficult to perform awake craniotomies and language testing in the majority of pediatric patients. In addition, children may be more prone to intraoperative seizures and exhibit afterdischarges more frequently during functional mapping using electrical cortical stimulation because of high stimulation thresholds needed to depolarize immature cortex. Moreover, choice of anesthetic regimen and doses may be different in pediatric patients, as is the effect of these drugs on immature brain; these factors add additional complexity in terms of interpretation and analysis of neurophysiologic recordings. Below, we are describing the modalities commonly used during intraoperative neurophysiologic testing in pediatric brain surgery, with emphasis on age-specific clinical indications, methodology, and challenges.

A lateralized alpha-band marker of the interference of exogenous attention over endogenous attention.

Scientists differentiate top-down from bottom-up visuospatial attention processes. While bottom-up attention is rapidly engaged by emerging demands from the environment, top-down attention in contrast reflects slow voluntary shifts of spatial attention. Several lines of research substantiate the idea that top-down and bottom-up attentional processes involve distinct functional systems. An increasing number of studies, however, argue that both attention systems share brain processing resources. The current study examines how salient visual events that engage bottom-up processes interfere with top-down attentional processes. Using neurophysiological recordings and multivariate pattern classification techniques, the authors show that these patterns of interference occur within the alpha-band of neural activity (8-12Hz), which implies that bottom-up and top-down attention processes share this narrow-band frequency brain resource. The results further demonstrate that patterns of alpha-band activity explains, in part, the interference between top-down and bottom-up attention at the behavioral level.

Implementation of [formula omitted]-Interval fourier transform analysis - Application to compound action potentials

N-Interval Fourier Transform Analysis (N-FTA) allows for spectral separation of a periodic target signal from uncorrelated background interference. A N-FTA pseudo-code is presented. The spectral resolution is defined by the repetition rate of the near periodic signal. Acceptance criteria for spectral targets were defined such that the probability of accepting false positives is less than 1500. Simulated and recorded neural compound action potentials (CAPs) were investigated. Simulated data allowed for comparison with reference solutions demonstrating the stability of N-FTA at conditions being comparable to real world data. Background activity was assessed with small errors. Evoked target components were assessed down to power spectral density being approximately N times below the background level. Validation was completed investigating a measured CAP. In neurophysiological recordings, this approach allows for accurate separation of near periodic evoked activity from uncorrelated background activities for frequencies below 1kHz.•N-FTA allows for spectral separation of a periodic target signal from uncorrelated interference by analyzing a segment containing N target signal repetitions.•A MATLAB implementation of the algorithm is provided along with simulated and recorded data.•N-FTA was successfully validated using simulated and measured data for CAPs.

Alterations of neural activity in the prefrontal cortex associated with deficits in working memory performance.

Working memory (WM), a core cognitive function, enables the temporary holding and manipulation of information in mind to support ongoing behavior. Neurophysiological recordings conducted in nonhuman primates have revealed neural correlates of this process in a network of higher-order cortical regions, particularly the prefrontal cortex (PFC). Here, we review the circuit mechanisms and functional importance of WM-related activity in these areas. Recent neurophysiological data indicates that the absence of these neural correlates at different stages of WM is accompanied by distinct behavioral deficits, which are characteristic of various disease states/normal aging and which we review here. Finally, we discuss emerging evidence of electrical stimulation ameliorating these WM deficits in both humans and non-human primates. These results are important for a basic understanding of the neural mechanisms supporting WM, as well as for translational efforts to developing therapies capable of enhancing healthy WM ability or restoring WM from dysfunction.

The Jena Audiovisual Stimuli of Morphed Emotional Pseudospeech (JAVMEPS): A database for emotional auditory-only, visual-only, and congruent and incongruent audiovisual voice and dynamic face stimuli with varying voice intensities.

We describe JAVMEPS, an audiovisual (AV) database for emotional voice and dynamic face stimuli, with voices varying in emotional intensity. JAVMEPS includes 2256 stimulus files comprising (A) recordings of 12speakers, speaking four bisyllabic pseudowords with six naturalistic induced basic emotions plus neutral, in auditory-only, visual-only, and congruent AV conditions. It furthermore comprises (B) caricatures (140%), original voices (100%), and anti-caricatures (60%) for happy, fearful, angry, sad, disgusted, and surprised voices for eight speakers and two pseudowords. Crucially, JAVMEPS contains (C) precisely time-synchronized congruent and incongruent AV (and corresponding auditory-only) stimuli with two emotions (anger, surprise), (C1) with original intensity (ten speakers, four pseudowords), (C2) and with graded AV congruence (implemented via five voice morph levels, from caricatures to anti-caricatures; eight speakers, two pseudowords). We collected classification data for Stimulus Set A from 22 normal-hearing listeners and four cochlear implant users, for two pseudowords, in auditory-only, visual-only, and AV conditions. Normal-hearing individuals showed good classification performance (McorrAV = .59 to .92), with classification rates in the auditory-only condition ≥ .38 correct (surprise: .67, anger: .51). Despite compromised vocal emotion perception, CI users performed above chance levels of .14 for auditory-only stimuli, with best rates for surprise (.31) and anger (.30). We anticipate JAVMEPS to become a useful open resource for researchers into auditory emotion perception, especially when adaptive testing or calibration of task difficulty is desirable. With its time-synchronized congruent and incongruent stimuli, JAVMEPS can also contribute to filling a gap in research regarding dynamic audiovisual integration of emotion perception via behavioral or neurophysiological recordings.

The open toolbox for behavioral research.

In this work, we describe a new open-source MATLAB toolbox for the control of behavioral experiments. The toolbox caters to very different types of experiments in different species, and with different underlying hardware. Typical examples are operant chambers in animals, with or without neurophysiology, behavioral experiments in human subjects, and neurophysiological recordings in humans such as EEG and fMRI. In addition, the toolbox supports communication via Ethernet to either control and monitor one or several experimental setups remotely or to implement distributed paradigms across different computers. This flexibility is possible, since the toolbox supports a wide range of hardware, some of which is custom developments. An example is a fast network-based digital-IO device for the communication with experimental hardware such as feeders or triggers in neurophysiological setups. We also included functions for online video analysis allowing paradigms to be contingent on responses to a screen, the head movement of a bird in an operant chamber, or the physical location of an animal in an open arena. While the toolbox is well tested and many components of it have been in use for many years, we do not see it as a finished product but rather a continuing development with a focus on easy extendibility and customization.

Inhibition of fatty acid binding protein-5 in the basolateral amygdala induces anxiolytic effects and accelerates fear memory extinction.

The endocannabinoid (eCB) system critically controls anxiety and fear-related behaviours. Anandamide (AEA), a prominent eCB ligand, is a hydrophobic lipid that requires chaperone proteins such as Fatty Acid Binding Proteins (FABPs) for intracellular transport. Intracellular AEA transport is necessary for degradation, so blocking FABP activity increases AEA neurotransmission. To investigate the effects of a novel FABP5 inhibitor (SBFI-103) in the basolateral amygdala (BLA) on anxiety and fear memory. We infused SBFI-103 (0.5μg-5μg) to the BLA of adult male Sprague Dawley rats and ran various anxiety and fear memory behavioural assays, neurophysiological recordings, and localized molecular signaling analyses. We also co-infused SBFI-103 with the AEA inhibitor, LEI-401 (3μg and 10μg) to investigate the potential role of AEA in these phenomena. Acute intra-BLA administration of SBFI-103 produced strong anxiolytic effects across multiple behavioural tests. Furthermore, animals exhibited acute and long-term accelerated associative fear memory extinction following intra-BLA FABP5 inhibition. In addition, BLA FABP5 inhibition induced strong modulatory effects on putative PFC pyramidal neurons along with significantly increased gamma oscillation power. Finally, we observed local BLA changes in the phosphorylation activity of various anxiety- and fear memory-related molecular biomarkers in the PI3K/Akt and MAPK/Erk signaling pathways. At all three levels of analyses, we found the functional effects of SBFI-103 depend on availability of the AEA ligand. These findings demonstrate a novel intra-BLA FABP5 signaling mechanism regulating anxiety and fear memory behaviours, neuronal activity states, local anxiety-related molecular pathways, and functional AEA modulation.

Comparing Parameters of Motor Potentials Recordings Evoked Transcranially with Neuroimaging Results in Patients with Incomplete Spinal Cord Injury: Assessment and Diagnostic Capabilities.

This study aimed to investigate the relationships between the different levels and degrees of incomplete spinal cord injury (iSCI) evaluated with magnetic resonance imaging (MRI) and the results of non-invasive electromyography (mcsEMG), motor-evoked potentials (MEP), and electroneurography (ENG). With a focus on patients with injuries at four different levels, C3-C5, C6-Th1, Th3-Th6, and Th7-L1, this research delved into the intricate interplay of spinal circuits and functional recovery. The study uses MEP, EMG, and ENG assessments to unveil the correlations between the MEP amplitudes and the MRI injury scores. We analysed data from 85 iSCI patients (American Spinal Injury Association-ASIA scale; ASIA C = 24, and D = 61). We compared the MRI and diagnostic neurophysiological test results performed within 1-2 months after the injury. A control group of 80 healthy volunteers was examined to establish reference values for the clinical and neurophysiological recordings. To assess the structural integrity of spinal white and grey matter on the transverse plane reconstructed from the sagittal readings, a scoring system ranging from 0 to 4 was established. The spinal cord was divided into two halves (left and right) according to the midline, and each half was further divided into two quadrants. Each quadrant was assessed separately. MEP and EMG were used to assess conduction in the corticospinal tract and the contraction properties of motor units in key muscles: abductor pollicis brevis (APB), rectus abdominis (RA), rectus femoris (RF), and extensor digitorum brevis muscles (EXT). We also used electroneurography (ENG) to assess peripheral nerve conduction and to find out whether the changes in this system significantly affect patients' scores and their neurophysiological status. The study revealed consistent positive correlations in iSCI patients between the bilateral decrease of the spinal half injury MRI scores and a decrease of the transcranially-evoked MEP amplitudes, highlighting the complex relationship between neural pathways and functional outcomes. Positive correlations are notably pronounced in the C3-C5, C6-Th1, and Th3-Th6 subgroups (mostly rs 0.5 and above with p < 0.05), while Th7-L1 presents distinct patterns (rs less than 0.5 and p being statistically insignificant) potentially influenced by unique structural compensation mechanisms. We also revealed statistically significant relationships between the decrease of the cumulative mcsEMG and MEP amplitudes and the cumulative ENG scores. These insights shed light on the multifaceted interactions between spinal cord injury levels, structural damage, neurophysiological measures, and motor function outcomes. Further research is warranted to unravel the intricate mechanisms driving these correlations and their implications for enhancing functional recovery and the rehabilitation algorithms in patients with iSCI.

Laminar pattern of adolescent development changes in working memory neuronal activity.

Adolescent development is characterized by an improvement in cognitive abilities, such as working memory. Neurophysiological recordings in a nonhuman primate model of adolescence have revealed changes in neural activity that mirror improvement in behavior, including higher firing rate during the delay intervals of working memory tasks. The laminar distribution of these changes is unknown. By some accounts, persistent activity is more pronounced in superficial layers, so we sought to determine whether changes are most pronounced there. We therefore analyzed neurophysiological recordings from the young and adult stage of male monkeys, at different cortical depths. Superficial layers exhibited an increased baseline firing rate in the adult stage. Unexpectedly, we also detected substantial increases in delay period activity in the middle layers after adolescence, which was confirmed even after excluding penetrations near sulci. Finally, improved discriminability around the saccade period was most evident in the deeper layers. These results reveal the laminar pattern of neural activity maturation that is associated with cognitive improvement.NEW & NOTEWORTHY Structural brain changes are evident during adolescent development particularly in the cortical thickness of the prefrontal cortex, at a time when working memory ability increases markedly. The depth distribution of neurophysiological changes during adolescence is not known. Here, we show that neurophysiological changes are not confined to superficial layers, which have most often been implicated in the maintenance of working memory. Contrary to expectations, substantial changes were evident in intermediate layers of the prefrontal cortex.

Neuromuscular recovery from botulism involves multiple forms of compensatory plasticity.

Botulinum neurotoxin (BoNT) causes neuroparalytic disease and death by blocking neuromuscular transmission. There are no specific therapies for clinical botulism and the only treatment option is supportive care until neuromuscular function spontaneously recovers, which can take weeks or months after exposure. The highly specialized neuromuscular junction (NMJ) between phrenic motor neurons and diaphragm muscle fibers is the main clinical target of BoNT. Due to the difficulty in eliciting respiratory paralysis without a high mortality rate, few studies have characterized the neurophysiological mechanisms involved in diaphragm recovery from intoxication. Here, we develop a mouse model of botulism that involves partial paralysis of respiratory muscles with low mortality rates, allowing for longitudinal analysis of recovery. Mice challenged by systemic administration of 0.7 LD50 BoNT/A developed physiological signs of botulism, such as respiratory depression and reduced voluntary running activity, that persisted for an average of 8-12 d. Studies in isolated hemidiaphragm preparations from intoxicated mice revealed profound reductions in nerve-elicited, tetanic and twitch muscle contraction strengths that recovered to baseline 21 d after intoxication. Despite apparent functional recovery, neurophysiological parameters remained depressed for 28 d, including end plate potential (EPP) amplitude, EPP success rate, quantal content (QC), and miniature EPP (mEPP) frequency. However, QC recovered more quickly than mEPP frequency, which could explain the discrepancy between muscle function studies and neurophysiological recordings. Hypothesizing that differential modulation of voltage-gated calcium channels (VGCC) contributed to the uncoupling of QC from mEPP frequency, pharmacological inhibition studies were used to study the contributions of different VGCCs to neurophysiological function. We found that N-type VGCC and P/Q-type VGCC partially restored QC but not mEPP frequency during recovery from paralysis, potentially explaining the accelerated recovery of evoked release versus spontaneous release. We identified additional changes that presumably compensate for reduced acetylcholine release during recovery, including increased depolarization of muscle fiber resting membrane potential and increased quantal size. In addition to identifying multiple forms of compensatory plasticity that occur in response to reduced NMJ function, it is expected that insights into the molecular mechanisms involved in recovery from neuromuscular paralysis will support new host-targeted treatments for multiple neuromuscular diseases.