Journal of Neurophysiology

Venegas, Joshua M.

doi: 10.1152/jn.00056.2024pmid: 38533966

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) is a developing field of research, with many current hypotheses receiving varying degrees of support. This syndrome affects ∼70% of astronauts both during and after long-duration space missions, resulting in impaired near vision and visual scotomas (blind spots). In this article, three prominent risk factors for SANS including zero gravity conditions, extraterrestrial hypercapnic environments, and individual genetic predisposition are described. These risk factors are then compared and their pathophysiological pathways are divided into five current hypotheses for the development of SANS. Finally, glymphatic system impairment is explored as a potential mutual end point for these pathways in the development of SANS.

Ogalo, Emmanuel; Linde, Lukas D.; Ro, Hannah; Ortiz, Oscar; Kramer, John L. K.; Berger, Michael J.

doi: 10.1152/jn.00472.2023pmid: 38353653

Movement-evoked pain is an understudied manifestation of musculoskeletal conditions that contributes to disability, yet little is known about how the neuromuscular system responds to movement-evoked pain. The present study examined whether movement-evoked pain impacts force production, electromyographic (EMG) muscle activity, and the rate of force development (RFD), during submaximal muscle contractions. Fifteen healthy adults (9 male, age = 30.3 ± 10.2; range = 22-59) performed submaximal isometric first finger abduction contractions without pain (baseline) and with movement-evoked pain induced by laser stimulation to the dorsum of the hand. Normalized force (% maximal voluntary contraction) and RFD decreased by 11% (p<0.001) and 15% (p=0.003), respectively, with movement-evoked pain, without any change in normalized peak EMG (p=0.77). Early contractile RFD, force impulse, and corresponding EMG amplitude computed within time segments of 50, 100, 150, 200ms relative to the onset of movement were also unaffected by movement-evoked pain (p>0.05). Our results demonstrate that movement-evoked pain impairs peak characteristics and not early measures of submaximal force production and RFD without affecting EMG activity (peak and early). Possible explanations for the stability in EMG with reduced force includes antagonist coactivation and a reorganization of motoneuronal activation strategy, which will be discussed herein.

Santhana Gopalan, Praghajieeth Raajhen; Xu, Weiyong; Waselius, Tomi; Wikgren, Jan; Penttonen, Markku; Nokia, Miriam S.

doi: 10.1152/jn.00356.2023pmid: 38533969

Learning outcome is modified by the degree to which the subject responds and pays attention to specific stimuli. Our recent research suggests that presenting stimuli in contingency with a specific phase of the cardiorespiratory rhythm might expedite learning. Specifically, expiration-diastole (EXP-DIA) is beneficial for learning trace eyeblink conditioning (TEBC) compared to inspiration-systole (INS-SYS) in healthy young adults. The aim of this study was to investigate whether the same holds true in healthy elderly adults (n = 50, aged >70 years). Participants were instructed to watch a silent nature film while TEBC trials were presented either at INS-SYS or EXP-DIA (separate groups). Learned responses were determined as eyeblinks occurring after the tone-conditioned stimulus (CS), immediately preceding the airpuff-unconditioned stimulus (US). Participants were classified as learners if they made at least five conditioned responses (CRs). Brain responses to the stimuli were measured using electroencephalogram (EEG). Memory for the film and awareness of the CS-US contingency were evaluated with questionnaires. As a result, participants showed robust brain responses to the CS, acquired CRs, and reported awareness of the CS-US relationship to a variable degree. There was no difference between the INS-SYS and EXP-DIA groups in any of the above. However, when only participants who learned were considered, those trained at EXP-DIA (n=11) made more CRs than those trained at INS-SYS (n=13). Thus, learned performance could be facilitated in those elderly who learned. However, training at a specific phase of cardiorespiratory rhythm did not increase the proportion of participants who learned.

Danielson, Tyler L.; Gould, Layla A.; DeFreitas, Jason M.; MacLennan, Rob J.; Ekstrand, Chelsea; Borowsky, Ron; Farthing, Jonathan P.; Andrushko, Justin W.

doi: 10.1152/jn.00407.2023pmid: 38505916

Introduction: The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI) we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Methods: Thirteen neurologically intact participants (age: 28 ± 6 years) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. Results: A repeated measures ANOVA demonstrated a significant main effect of force (p = 0.012, ηp2 = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t-tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. Conclusions: We show evidence of task dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.

Lieu, Brandon; Everaert, Dirk G.; Ho, Chester; Gorassini, Monica A.

doi: 10.1152/jn.00436.2023pmid: 38505867

On demand and localized treatment for excessive muscle tone after spinal cord injury (SCI) is currently not available. Here we examine the reduction in leg hypertonus in a person with mid-thoracic, motor-complete SCI using a commercial transcutaneous electrical stimulator (TES) applied at 50 or 150-Hz to the lower back and the possible mechanisms producing this bilateral reduction in leg tone. Hypertonus of knee extensors without and during TES, with both cathode and anode placed over the spinal column (MID) or 10-cm to the left of midline (LAT) to only active underlying skin and muscle afferents, was simultaneously measured in both legs with the pendulum test. Spinal reflexes mediated by proprioceptive (H-reflex) and cutaneomuscular (CMR) afferents were examined in the right leg opposite to the applied LAT TES. Hypertonus disappeared in both legs but only during thoracolumbar TES, and even during LAT TES. The marked reduction in tone was reflected in the greater distance both lower legs first dropped to after being released from a fully extended position, increasing by 172.8% and 94.2% during MID and LAT TES, respectively, compared to without TES. Both MID and LAT (left) TES increased H-reflexes but decreased the first burst, and lengthened the onset of subsequent bursts, in the cutaneomuscular reflex of the right leg. Thoracolumbar TES is a promising method to decrease leg hypertonus in chronic, motor-complete SCI without activating spinal cord structures and may work by facilitating proprioceptive inputs that activate excitatory interneurons with bilateral projections that in turn recruit recurrent inhibitory neurons.

Deutsch, Andrew J.

doi: 10.1152/jn.00482.2023pmid: 38533934

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motoneuron death. Motoneuron excitability dysfunction in ALS is suspected to contribute to motoneuron degeneration. Therefore, mechanisms underlying excitability dysfunction are being thoroughly investigated. A recent publication from Trajano et al. (Trajano, G. S., Orssatto, L. B. R., McCombe, P. A., Rivlin, W., Tang, L., & Henderson, R. D. The Journal of Physiology, 2023) examined temporal changes to persistent inward currents (PICs) in ALS patients. They show that delta F (an estimate of PICs) has opposite temporal trends in stronger and weaker muscles of ALS patients. This study is very important to aid in the understanding of disease mechanisms. This Neuro Forum article explores some important considerations for interpreting the results of this study, including treatment effects, potential sex differences, and a lack of comparison to healthy individuals.

Williams, Kristin S.

doi: 10.1152/jn.00404.2023pmid: 38533950

This article evaluates the ethical implications of utilizing artificial intelligence (AI) algorithms in neurological diagnostic examinations. Applications of AI technology have been utilized to aid in the determination of pharmacological dosages of gadolinium for brain lesion detection, localization of seizure foci, and the characterization of large vessel occlusion in ischemic stroke patients. Multiple subtypes of AI/machine learning (ML) algorithms are analyzed, as AI-assisted neurology utilizes supervised, unsupervised, artificial neural network (ANN), and deep neural network (DNN) learning models. As ANN and DNN analyses can be applied to data with an unknown clinical diagnosis, these algorithms are evaluated according to Bayesian statistical analyses. Bayesian neural network analyses are incorporated, as these algorithms indicate that the predictive accuracy and model performance are dependent upon accurate configurations of the model’s hyperparameters and neural inputs. Thus, mathematical evaluations of AI algorithms are comprehensively explored to examine their clinical utility, as underperformance of AI/ML models may have deleterious consequences that affect patient outcomes due to misdiagnosis and false-negative test results.

Gómez, Diana Margarita Casas; Braidot, Ariel Andrés Antonio

doi: 10.1152/jn.00121.2023pmid: 38323330

To evaluate Mirror Visual Feedback (MVF) as a training tool for brain-computer interface (BCI) users. Because about 20%-30% of subjects need more training to operate a BCI system that uses motor imagery. Electroencephalograms (EEGs) were recorded from 18 healthy subjects, using event-related desynchronization (ERD) to observe the responses during the movement or movement intention of the hand for the conditions of Control, Imagination, and the MVF with the mirror box. Two groups of subjects were formed, Group 1: control, imagination, and MVF. Group 2: control, MVF, and imagination. There were significant differences in imagination conditions between groups using MVF before or after imagination (Right-hand p= 0.0403. Left-hand p=0.00939). The illusion of movement through MVF is not possible in all subjects, but even in those cases, we found an increase in imagination when the subject used the MVF previously. The increase in the r2s of imagination in the right and left hands suggests cross-learning. The increase in motor imagery recorded with EEG after MVF suggests that the mirror box made it easier to imagine movements. Our results provide evidence that the MVF could be used as a training tool to improve motor imagery.

Shi, Kaiwen; Quass, Gunnar L.; Rogalla, Meike M.; Ford, Alexander N.; Czarny, Jordyn E.; Apostolides, Pierre F.

doi: 10.1152/jn.00013.2024pmid: 38505907

The inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. The IC's non-lemniscal, dorsal "shell" region is likely important for this process, as neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals to the amygdala and non-primary auditory cortices; forebrain circuits important for vocalization coding in a variety of mammals, including humans. However, the extent to which shell IC neurons transmit acoustic features necessary to discern vocalizations is less clear, owing to the technical difficulty of recording from neurons in the IC's superficial layers via traditional approaches. Here we use 2-photon Ca2+ imaging in mice of either sex to test how shell IC neuron populations encode the rate and depth of amplitude modulation, important sound cues for speech perception. Most shell IC neurons were broadly tuned, with a low neurometric discrimination of amplitude modulation rate; only a subset were highly selective to specific modulation rates. Nevertheless, neural network classifier trained on fluorescence data from shell IC neuron populations accurately classified amplitude modulation rate, and decoding accuracy was only marginally reduced when highly tuned neurons were omitted from training data. Rather, classifier accuracy increased monotonically with the modulation depth of the training data, such that classifiers trained on full-depth modulated sounds had median decoding errors of ~0.2 octaves. Thus, shell IC neurons may transmit time-varying signals via a population code, with perhaps limited reliance on the discriminative capacity of any individual neuron.

Dong, Juchuan; Dong, Yifei; An, Lijuan; Wang, Yufan; Li, Yongmei; Jin, Lihua

doi: 10.1152/jn.00054.2024pmid: 38568478

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, Environmental Enrichment (EE) is strictly considered a form of sensory intervention. However, limited research employs EE as a single sensory input intervention to validate outcomes post-intervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions use in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as a neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. Additionally, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared to the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.