Journal of neurophysiology最新文献

Taking sport climbing as a testbed, we explored coarticulation in naturalistic motor-behavior at the level of whole-body kinematics. Participants were instructed to execute a series of climbing routes, each composed of two initial foot-moves equal in all routes, and two subsequent hand-moves differing across routes in a set of eight possible configurations. The goal was assessing whether climbers modulate the execution of a given move depending on which moves come next in the plan. Coarticulation was assessed by training a set of classifiers and estimate how well the whole-body (or single-joint) kinematics during a given stage of the climbing execution could predict its future unfolding. Results showed that most participants engage in coarticulation, with temporal and bodily patterns that depend on expertise. Non-climbers tend to prepare the next-to-come move right before its onset and only after the end of the previous move. Rather, expert-climbers (and to a smaller extent, beginner-climbers) show early coarticulation during the execution of the previous move and engage in adjustments that involve the coordination of a larger number of joints across the body. These results demonstrate coarticulation effects in whole-body naturalistic motor behavior and as a function of expertise for the first time. Furthermore, the enhanced coarticulation found in expert-climbers provides hints for experts engaging in more refined mental processes converting abstract instructions (e.g., move the right hand to a given location) into motor simulations involving whole-body coordination. Overall, these results contribute to advancing our current knowledge of the rich interplay between cognition and motor control.

Angiogenesis may play an important role in the pathophysiology of Alzheimer's disease (AD). Previous in vitro and in vivo studies suggest a link between angiogenesis and cerebral blood flow (CBF) in AD; however, this has never been studied clinically. In this sample of study participants with early AD (n = 15), serum vascular endothelial growth factor (VEGF), an angiogenesis biomarker, was negatively associated with regional CBF (rCBF) in the angular gyrus even after bootstrapping at a repetition of 5000 and controlling for age, sex, and diagnosis (β = -0.015, SE = 0.006, p = .02, f²= 0.27, p_bootstrapped = .049). Sex-stratified subgroup analyses showed a strong negative correlation between rCBF in the angular gyrus and log-VEGF in males (n = 7; r = -0.78, p = .04), but not in females (n = 8; r = -0.16, p = .7). These results support an association between angiogenesis and CBF in early AD that should be further investigated in longitudinal studies and may have relevance for future therapeutic interventions in AD.

Psychedelics are known to induce profound perceptual distortions, yet the neural mechanisms underlying these effects, particularly within the auditory system, remain poorly understood. In this study, we investigated the effects of the psychedelic compound 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin 2A receptor agonist, on the activity of neurons in the auditory cortex of awake mice. We examined whether DOI administration alters sound-frequency tuning, variability in neural responses, and deviance detection (a neural process reflecting the balance between top-down and bottom-up processing). Our results show that whereas DOI does not alter the frequency selectivity of auditory cortical neurons in a consistent manner, it increases trial-by-trial variability in responses and consistently diminishes the neural distinction between expected (standard) and unexpected (oddball) stimuli. This reduction in deviance detection was primarily driven by a decrease in the response to oddball sounds, suggesting that DOI dampens the auditory cortex's sensitivity to unexpected events. These findings provide insights into how psychedelics disrupt sensory processing and shed light on the neural mechanisms underlying the altered perception of auditory stimuli observed in the psychedelic state.NEW & NOTEWORTHY The neural basis of perceptual distortions induced by psychedelics remains poorly understood. This study demonstrates that the serotonergic psychedelic DOI increases neural response variability and impairs deviance detection in the auditory cortex by reducing sensitivity to unexpected sounds. These findings provide new insights into how psychedelics disrupt sensory processing and alter the balance between bottom-up and top-down neural signaling, contributing to our understanding of altered perception in the psychedelic state.

Lumbar transcutaneous spinal cord stimulation (TSS) evokes synchronized muscle responses, termed spinally evoked motor response (sEMR). Whether the structures TSS activates to evoke sEMRs differ when TSS intensity and waveform are varied is unknown. In 15 participants (9 F, 6 M), sEMRs were evoked by TSS over L1-L3 (at sEMR threshold and suprathreshold intensities) with conventional (one 400-µs biphasic pulse) or high-frequency burst (ten 40-µs biphasic pulses at 10 kHz) stimulus waveforms in vastus medialis (VM), tibialis anterior (TA), and medial gastrocnemius (MG) muscles. TSS was paired with transcranial magnetic stimulation (TMS) over the contralateral motor cortex at relative interstimulus intervals (ISIs) (-10 ms to 11 ms), centered on the ISI when TSS and TMS inputs simultaneously activated VM motoneurons. Doublet TSS was delivered at 80-ms ISI. For VM, the area of the combined response evoked by paired TMS and TSS was not facilitated at any ISI. For TA and MG, combined responses were facilitated by ∼40-100% when TMS activated the motoneurons before or at a similar time as TSS, particularly with suprathreshold TSS. Additionally, for TA, there was greater suppression of the second sEMR evoked by TSS doublets using suprathreshold conventional TSS compared to high-frequency burst TSS (P < 0.001). The results suggest that for VM TSS activated predominantly motor axons, but for TA and MG facilitation of the sEMR by TMS suggests that TSS activated sensory axons. Stimulation waveforms had similar outcomes in most conditions.NEW & NOTEWORTHY Transcutaneous spinal cord stimulation (TSS) can evoke muscle responses by activation of sensory and/or motor axons. The relative contribution of these varies across the muscles tested. We found evidence for activation of sensory axons with TSS for tibialis anterior and medial gastrocnemius but not for vastus medialis. In cases where sensory axons were activated, conventional TSS activated relatively more sensory axons than high-frequency burst TSS.

Humans possess a unique ability to manipulate tools to help us navigate the world around us. This ability is facilitated by the dexterity of our hands. However, millions lose this capability annually due to conditions like limb amputation or cerebral vascular accident (i.e., stroke). This great loss of human hand function has led to increased study of human hand action. Although previous research focused on coordinated hand motion, known as synergies, during reaching and grasping, manipulation of complex objects remains understudied. Specifically, we aimed to test two hypotheses: 1) the number of synergies underlying manipulation is the same as those underlying reach-and-grasp, and 2) the identity of synergies underlying manipulation is different from those underlying reach-and-grasp. To do so, we measured human hand motion during two experiments: 1) during reach and grasp of a tool or object commonly used in wire harness installation and 2) during manipulation of those objects and tools to install a wire harness on a mock electrical cabinet. Results showed that manipulation generally required more synergies than grasp. Comparison between reach-and-grasp and manipulation revealed a decrease in synergy similarity with synergy-order. Considering that higher-order synergies become significant during manipulation, it is important that we investigate these differences; this study serves as a point of entry to doing so. If we want our prosthetic and rehabilitative devices to restore hand function to those who have lost it, we must study hand function, specifically manipulation, and not just grasping.NEW & NOTEWORTHY This study uncovers new insights into kinematic synergies during functional human hand manipulation of objects and tools, through the study of wire harness installation. It emphasizes the nuanced distinctions between functional hand manipulation and simple grasping, revealing that manipulation tasks require a greater number and distinct subset of hand synergies compared with simple grasp actions. This research marks a significant step toward appreciating the intricacies of hand coordination in complex tasks beyond grasping.

Visuocortical responses are regulated by gain control mechanisms, giving rise to fundamental neural and perceptual phenomena such as surround suppression. Suppression strength, determined by the composition and relative properties of stimuli, controls the strength of neural responses in early visual cortex, and in turn, the subjective salience of the visual stimulus. Notably, suppression strength is modulated by feature similarity; for instance, responses to a center-surround stimulus in which the components are collinear to each other are weaker than when they are orthogonal. However, this feature-tuned aspect of normalization, and how it may affect the gain of responses, has been understudied. Here, we examine the contribution of the tuned component of suppression to contrast response modulations across the visual field. To do so, we used functional magnetic resonance imaging (fMRI) to measure contrast response functions (CRFs) in early visual cortex (areas V1-V3) in 10 observers while they viewed full-field center-surround gratings. The center stimulus varied in contrast between 2.67% and 96% and was surrounded by a collinear or orthogonal surround at full contrast. We found substantially stronger suppression of responses when the surround was parallel to the center, manifesting as shifts in the population CRF. The magnitude of the CRF shift was strongly dependent on voxel spatial preference and seen primarily in voxels whose receptive field spatial preference corresponds to the area straddling the center-surround boundary in our display, with little-to-no modulation elsewhere.NEW & NOTEWORTHY Visuocortical responses are underpinned by gain control mechanisms. In surround suppression, it has been shown that suppression strength is affected by the orientation similarity between the center and surround stimuli. In this study, we examine the impact of orientation-tuned suppression on population contrast responses in early visual cortex and its spread across the visual field. Results show stronger suppression in parallel stimulus configurations, with suppression largely isolated to voxels near the center-surround boundary.

Analyzing reaction time distributions can provide insights into decision-making processes in the brain. The Linear Approach to Threshold with Ergodic Rate (LATER) model is arguably the simplest model for predicting reaction time distributions and can summarize distributions with as few as two free parameters. However, the coordinates for visualizing and fitting distributions with LATER ("reciprobit" space) are irregular, making the application of this simple model inaccessible to those without a programming background. Here we describe an open-source R package, LATERmodel, that allows for easy visualization of reaction time distributions, along with fitting of these with the LATER model. Using canonical data from the literature, we show that our tool replicates key features from previous LATER analysis tools, while also providing more robust fitting procedures and a more flexible method for fitting subpopulations of very rapid, early responses. Although all features of LATERmodel can be used directly in the statistical programming language R, key features are also available through a RShiny graphical user interface to allow researchers without programming background to apply the LATER model to their reaction time data.NEW & NOTEWORTHY Analyzing reaction time distributions provides a powerful tool for investigating decision-making processes. Here we describe an open-source toolbox to allow the Linear Approach to Threshold with Ergodic Rate (LATER) model, the simplest principled model linking reaction times and decisions, to be applied to empirical reaction time data, including by clinicians and scientists without any programming experience.

Lab rodent species commonly used to study the visual system and its development (hamsters, rats, and mice) are crepuscular/nocturnal, altricial, and possess simpler visual systems than carnivores and primates. To widen the spectra of studied species, here we introduce an alternative model, the Chilean degu (Octodon degus). This diurnal, precocial Caviomorph rodent has a cone-enriched, well-structured retina, and well-developed central visual projections. To assess degus' visual physiological properties, we characterized the visual responses and receptive field (RF) properties of isolated neurons in the superficial layers of the superior colliculus (sSC). To facilitate comparison with studies in other rodent species, we used four types of stimuli: 1) a moving white square, 2) sinusoidal gratings, 3) an expanding black circle (looming), and 4) a stationary black circle. We found that as in other mammalian species, RF size increases from superficial to deeper SC layers. Compared with other lab rodents, degus sSC neurons had smaller RF sizes and displayed a broader range of spatial frequency (SF) tunings, including neurons tuned to high SF (up to 0.24 cycles/deg). Also, unlike other rodents, approximately half of sSC neurons exhibited linear responses to contrast. In addition, sSC units showed transient ON-OFF responses to stationary stimuli but increased their firing rates as a looming object increased in size. Our results suggest that degus have higher visual acuity, higher SF tuning, and lower contrast sensitivity than commonly used nocturnal lab rodents, positioning degus as a well-suited species for studies of diurnal vision that are more relevant to humans.NEW & NOTEWORTHY Rodent species commonly used to study vision are crepuscular/nocturnal, altricial, and possess simpler visual systems than diurnal mammals. Here we introduce an alternative model, the diurnal, precocial, Octodon degus, a Caviomorph rodent with a well-developed visual system. In this study, we characterize the visual responses of the degus' superior colliculus. Our results suggest that degus have higher visual acuity than nocturnal rodents, positioning degus as a well-suited species for studies of human-like diurnal vision.

Despite a significant genetic component to insomnia (heritability: 22%-25%), the genetic loci that modulate insomnia risk remain limited. We used the Unified Test for Molecular Markers (UTMOST) for transcriptome-wide association studies (TWAS) across various tissues, integrating summary statistics from a Genome-Wide Association Study (GWAS) of 462,341 European participants with gene expression data from the Genotype-Tissue Expression (GTEx) project. Three validation methods (FUSION, FOCUS, and MAGMA) were used to confirm important genes. Tissue and functional enrichment analyses of insomnia-related single-nucleotide polymorphisms (SNPs) were conducted with MAGMA. Conditional and joint analyses, along with fine mapping, were used to enhance our understanding of insomnia's genetic architecture. Mendelian randomization was used to assess causal associations between significant genes and insomnia. Two novel susceptibility genes, VRK2 and MMRN1, were identified as linked to insomnia risk using four TWAS approaches. Mendelian randomization analysis suggests VRK2 increases the risk of insomnia. Tissue enrichment analyses indicated that insomnia-related SNPs were enriched in specific brain regions, including the cerebellum, frontal cortex (BA9), hypothalamus, and hippocampus. Conditional and joint analyses identified two genomic regions (2p16.1 and 4q22.1). Functional enrichment analyses showed that pathways related to insomnia involve the SMAD2/3 pathway, synaptic function, and oxidative stress. This study identifies two new candidate genes, VRK2 and MMRN1, that may contribute to insomnia risk through neurodevelopment, neuroinflammation, and synaptic function, suggesting potential therapeutic targets.NEW & NOTEWORTHY This study identifies VRK2 and MMRN1 as novel susceptibility genes for insomnia through transcriptome-wide association studies (TWAS). Mendelian randomization confirms a causal link between VRK2 and insomnia. Key brain regions, including the cerebellum and frontal cortex, and critical pathways like SMAD2/3 signaling and oxidative stress are implicated. These findings provide new insights into the genetic basis of insomnia.

Low-level tragus stimulation (LL-TS) as a noninvasive technique of vagus nerve stimulation (VNS) moves to the fore in the autonomic nervous system (ANS) studies as a nondrug based, easy applicable tool. LL-TS triggering a complex systemic response may offer a broader cardioprotective potential than expected as a recent investigation outlined blood pressure (BP) reduction by LL-TS in patients with hypertension, which is commonly related to imbalance of the ANS as several other cardiovascular diseases.