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Nakazawa, K.

Publications and source records attributed to Nakazawa, K..

At least 19 recordsLinked to original sources

Height-induced postural threat selectively facilitates spinal reflex in the tibialis anterior muscle during quiet standing

Long-latency stretch reflex and corticospinal excitability in the tibialis anterior muscle (TA) are facilitated when balance is threatened, even without background TA activity, suggesting supraspinal modulation as preparatory tuning for ankle stabilization. However, it remains unclear whether such tuning is evident at the spinal level and specific to the TA among lower-limb muscles. We therefore examined the effects of height-induced postural threat on multi-segmental monosynaptic spinal reflexes (MMR) in lower-limb muscles during quiet standing. Seventeen healthy young males performed 90-s standing tasks under three postural threat conditions, created by combining real and virtual reality (VR) heights: (1) Low-threat (real ground & VR ground), (2) Medium-threat (real table & VR ground), and (3) High-threat (real table & VR bridge). During each condition, transcutaneous spinal cord stimulation (tSCS) was applied to the lumbar spine to elicit MMR in lower-limb muscles. Electromyograms (EMG) were recorded from six muscles of the right leg: vastus medialis (VM), biceps femoris (BF), TA, soleus (SOL), medial (MG), and lateral gastrocnemius (LG). MMR excitability was quantified as peak-to-peak EMG amplitude. Fear ratings and electrodermal activity were higher in High-threat than Low-threat (all p < 0.05), confirming successful threat induction. Peak-to-peak EMG amplitude in the TA was significantly higher in High-threat than Low-threat (17.1% increase, p = 0.0393), whereas background TA activity remained absent across conditions. These results indicate that TA has unique function to facilitate spinal excitability as a preparatory tuning for ankle stabilization. Key pointsO_LIPrevious studies have shown the supraspinal facilitation of the tibialis anterior muscle without background muscle activation as a preparatory tuning for ankle stabilization. C_LIO_LITo test the hypothesis that such tuning is also evident at the spinal level and specific to the tibialis anterior muscle, this study examined whether height-induced postural threat modulates multi-segmental monosynaptic reflex excitability in lower-limb muscles using transcutaneous spinal cord stimulation. C_LIO_LIElectrodermal activity and fear ratings increased under height-induced postural threat, confirming the successful induction of postural threat. C_LIO_LIUnder height-induced postural threat, the multi-segmental monosynaptic reflex was selectively facilitated in the tibialis anterior muscle, while its background activity remained absent. C_LIO_LIOur findings demonstrate selective facilitation of spinal excitability in the tibialis anterior muscle, which may serve as preparatory tuning for ankle stabilization under threat to balance. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/742625v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@19fde78org.highwire.dtl.DTLVardef@c6aa8dorg.highwire.dtl.DTLVardef@e73a76org.highwire.dtl.DTLVardef@af393d_HPS_FORMAT_FIGEXP M_FIG C_FIG Abstract figure legendWhen balance is threatened, corticospinal excitability and long-latency stretch reflex in the tibialis anterior muscle (TA) are facilitated even in the absence of background TA activity, suggesting supraspinal preparatory tuning for ankle stabilization. This study tested the hypothesis that such facilitation is also expressed at the spinal level and is specific to the TA. Participants completed 90-s quiet standing trials under three different height-induced postural threat conditions. During each trial, transcutaneous spinal cord stimulation was delivered over the lumbar spine to elicit multi-segmental monosynaptic reflexes (MMR) in multiple lower-limb muscles. High-threat condition increased fear ratings and electrodermal activity, indicating successful threat induction. Moreover, MMR excitability was selectively increased in the TA under High-threat condition despite the absence of background TA activity. These findings suggest that spinal facilitation is selectively expressed in the TA and may reflect preparatory tuning for ankle stabilization under threat to balance.

neuroscience↗

Spatiotemporal spinal integration of descending and spinal volleys in spinal motor circuits revealed by compound motor evoked potentials

Descending corticospinal and afferent pathways underlying spinally evoked motor potential both contribute to motor output, yet how their interaction at the spinal and peripheral levels is organized spatially within a muscle remains unclear. This study investigated the spatiotemporal characteristics of descending modulation of spinally evoked motor potentials by combining subthreshold transcranial magnetic stimulation (TMS) with transcutaneous spinal cord stimulation (tSCS). In Experiment 1, spinally evoked motor potentials were recorded from multiple lower-limb muscles at various interstimulus intervals (ISIs) defined relative to central conduction time (CCT). Subthreshold TMS facilitated spinally evoked motor potentials from CCT onward across all recorded muscles, with additional bilateral facilitation observed at longer ISIs. In Experiment 2, high-density surface electromyography (HDsEMG) revealed distinct intramuscular activation patterns in the tibialis anterior. The center of gravity (CoG) of TMS-induced motor evoked potentials was located more proximally than that of spinally evoked motor potentials. Notably, the CoG of facilitation maps was shifted further proximally than that of both single-stimulus responses. These findings suggest that descending and afferent inputs preferentially recruit partially distinct motoneuron pools within the same muscle. The proximal bias of facilitation indicates recruitment of additional motoneurons rather than uniform amplification of existing activity. Together, these results demonstrate that the interaction between descending and afferent inputs is both timing-dependent and spatially non-uniform, providing new insight into sensorimotor integration in the human lower limb.

neuroscience↗

Two-Dimensional Phase Separation of DNA Nanomotifs Anchored to Lipid Bilayers

Spatial organization and temporal regulation of membrane components are essential for achieving complex functions in artificial cells, such as cell division and signalling. DNA-based molecular tools provide a powerful means to control biomolecular interactions with high precision. Here, we investigate the phase behavior of cholesterol-modified, star-shaped DNA nanomotifs anchored to the lipid bilayers of giant unilamellar vesicles (GUVs), by using fluorescence confocal microscopy and cryo-electron microscopy. These motifs spontaneously anchor to the lipid bilayers via hydrophobic interactions and exhibit distinct spatial organization depending on their sticky end sequences. Motifs with complementary sticky end sequences interact and distribute uniformly, while orthogonal motifs with different sticky end sequences segregate into isolated gel-like domains with limited lateral mobility. Notably, the phase separation of motifs does not require lipid phase separation, indicating that DNA-driven organization can take place independently of lipid phase separation. The behavior of this system is governed by the interplay of three key parameters: (i) hydrophobic anchoring via cholesterol, (ii) electrostatic repulsion between negatively charged DNA nanomotifs, and (iii) sticky end interactions. The observed two-dimensional phase separation of orthogonal DNA nanomotifs at the GUV interface presents a novel strategy for controlling lateral membrane organization in GUV systems. This approach would offer flexibility in membrane composition and enables molecular positioning, thereby achieving a high degree of organization on the surface in artificial cell models.

biophysics↗

Cortical and spinal contributions to remote interlimb facilitation in humans

Voluntary contraction in one limb can facilitate motor output in a distant limb, a phenomenon commonly referred to as the remote effect. However, the neural mechanisms underlying this remote interlimb facilitation remain unclear. This study investigated cortical and spinal contributions to the remote effect in able-bodied participants. Transcranial magnetic stimulation (TMS) was applied over the hand area of the primary motor cortex using posterior-anterior (PA) and anterior-posterior (AP) current directions, which are sensitive to different cortical inputs. Cortical excitability was assessed using single- and paired-pulse paradigms to measure short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), and short-latency afferent inhibition (SAI). Spinal motoneuron excitability was assessed from F-waves elicited by peripheral nerve stimulation. During voluntary lower-limb contractions, single-pulse TMS elicited larger motor evoked potentials in hand muscles across current directions, indicating a broad increase in net corticospinal output. However, only AP-sensitive paired-pulse measures showed reduced SICI and enhanced SICF during contraction, whereas PA-sensitive SICI and SICF were not significantly altered, suggesting that cortical modulation during the remote effect is expressed more clearly in AP-sensitive measures. SAI with PA stimulation was less consistently expressed during contraction, suggesting that afferent-related inhibitory modulation may also be influenced during the remote effect. In parallel, F-wave amplitude and persistence increased, consistent with enhanced spinal motoneuron excitability. Together, these results provide converging evidence that the remote effect in humans involves broad corticospinal and spinal facilitation, accompanied by current direction-dependent modulation of cortical excitability measures. KEY POINTS SUMMARYO_LIVoluntary contraction in one limb can facilitate motor output in a distant limb, but the mechanisms underlying this remote interlimb facilitation remain unclear. C_LIO_LIWe tested whether remote lower-limb contraction modulates corticospinal output, intracortical excitability, and spinal motoneuron excitability in a resting hand muscle. C_LIO_LISingle-pulse transcranial magnetic stimulation showed that motor evoked potentials in the hand were facilitated during remote lower-limb contraction across multiple current directions, indicating a broad increase in net corticospinal output. C_LIO_LIPaired-pulse measures were modulated preferentially with anterior-posterior stimulation, with reduced short-interval intracortical inhibition and increased short-interval intracortical facilitation, suggesting current direction-dependent modulation of cortical excitability measures. C_LIO_LIF-wave amplitude and persistence were also enhanced during remote lower-limb contraction, indicating increased spinal motoneuron excitability. These findings provide converging evidence that the remote effect involves both cortical and spinal contributions. C_LI

neuroscience↗

Distinct neural input strategies to motor units in the soleus and medial gastrocnemius during quiet standing

Standing posture control critically depends on the activation of the soleus (SOL) and medial gastrocnemius (MG), which serve distinct functional roles. Identifying underlying neural mechanisms has been challenging, as conventional invasive techniques sample only limited motor units (MUs). Recent advances in high-density surface electromyography (HDsEMG) have enabled analysis of MU activity and estimation of common synaptic inputs to spinal motoneurons. Therefore, we aimed to elucidate the common synaptic inputs underlying the distinct MU behaviors of SOL and MG during standing. We recorded HDsEMG from the SOL and MG, alongside electroencephalography, from 20 male participants during standing and isometric voluntary contractions. EMG signals were decomposed into individual MU activity, with common synaptic inputs estimated through intramuscular and corticomuscular coherence analyses (IMC and CMC). Compared to SOL, the MG exhibited significantly higher delta-, alpha-, and beta-band IMC during standing. In task comparisons, alpha-band IMC increased during standing specifically in the MG. Furthermore, although beta-band CMC decreased in both muscles while standing, IMC was preserved in the MG but markedly reduced in SOL. This dissociation suggests that the common neural drive to the MG during standing is likely derived from subcortical rather than cortical pathways. These results demonstrate that the SOL and MG are governed by distinct neural control strategies, which likely underlie their functional roles. Given the low CMC, the MG relies on strong common synaptic input from subcortical pathways (e.g., vestibulospinal and reticulospinal) to produce rapid corrective torque, whereas the SOL functions with lower neural synchrony to ensure steady ankle stiffness. Key pointsO_LIThe soleus and medial gastrocnemius play distinct roles in standing control, however, due to technical limitations, it has been difficult to identify the underlying neural mechanisms responsible for these differences. C_LIO_LIUsing high-density surface electromyography, we examined motor unit activity and neural inputs to these muscles during standing. C_LIO_LIThe medial gastrocnemius shows greater common synaptic input, potentially facilitating rapid ankle plantarflexion torque generation to correct postural sway. C_LIO_LIThe soleus exhibits lower motor unit synchrony, enabling stable and continuous ankle plantarflexion torque generation for body weight support. C_LIO_LIThis study demonstrates that the soleus and medial gastrocnemius are governed by distinct neural control strategies, which likely underlie their distinct functional roles. C_LI Abstract figure legend O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/698550v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@be53aorg.highwire.dtl.DTLVardef@f6793aorg.highwire.dtl.DTLVardef@190e8f9org.highwire.dtl.DTLVardef@af5e4b_HPS_FORMAT_FIGEXP M_FIG C_FIG Motor unit spike trains were decomposed from high-density surface electromyograms recorded from the medial gastrocnemius (MG; left; red) muscle and soleus (SOL; right; blue). To compare the neural input to the spinal motor neurons between them, we quantified the intramuscular coherence (IMC) of motor unit spike trains within the delta, alpha, and beta bands. MG exhibited greater IMC than SOL during standing, indicating stronger common synaptic input, likely mediated by vestibulospinal and reticulospinal pathways. In contrast, SOL showed lower IMC, suggesting a greater contribution of independent synaptic input. As a consequence, high motor-unit synchrony in the MG supports rapid, phasic torque generation for postural sway attenuation, whereas low synchrony in the SOL enables smooth, steady torque production for weight bearing during standing.

physiology↗

Facilitating the Supplementary Motor Area Activity Reduces Variability of Ball Arrival Position in Accurate Ball Throwing Performance

Maintaining high accuracy during rapid, dynamic movements is a significant challenge for the central nervous system. The supplementary motor area (SMA) is a key cortical region for orchestrating motor commands and regulating movement variability, yet its causal role in maintaining precision during high-speed tasks remains to be fully elucidated. We investigated the impact of modulating SMA excitability on throwing performance in fourteen healthy adults with no competitive throwing experience. Participants performed maximal and submaximal (50% effort) throwing tasks before and after receiving intermittent (facilitatory) or continuous (inhibitory) theta burst stimulation (TBS) over the SMA. Outcome measures included ball speed, variability of pitch location--quantified as variable error (95% confidence ellipse area) and absolute error (Euclidean distance from the ellipse center to the target)--and introspective ratings of performance via visual analog scales (VAS). Results showed that intermittent TBS (iTBS) significantly reduced the variable error of pitch location during maximal-effort throwing--where neural noise is theoretically elevated--without compromising ball speed. In contrast, no significant changes in performance were observed following continuous TBS or during the submaximal throwing task. Notably, objective precision gains under iTBS were dissociated from subjective ratings of accuracy, which increased globally over time independent of stimulation type. These findings demonstrate that the SMA plays a critical causal role in stabilizing motor output under high motor drive. This study suggests that SMA-mediated stabilization operates as a subconscious process, offering new insights for optimizing complex motor skills. HighlightsO_LIiTBS over the SMA significantly reduces throwing variable error in novices. C_LIO_LIImproved precision occurs without compromising maximal ball throwing speed. C_LIO_LIThe SMA causally stabilizes motor output during high-speed movements. C_LIO_LIObjective precision gains are dissociated from subjective performance ratings. C_LIO_LISMA-mediated stabilization operates as a subconscious motor process. C_LI

neuroscience↗

Musicianship and active musical engagement predict facilitation of auditory-motor plasticity: evidence from auditory-motor paired associative stimulation

Background and AimAuditory-motor paired associative stimulation (PAS) probes experience-dependent plasticity in auditory-motor circuits. We tested whether musical experience and musical sophistication modulate PAS-induced facilitation when instrument tones are paired with transcranial magnetic stimulation (TMS) over the left primary motor cortex. MethodSixteen musicians and thirteen non-musicians completed two sessions. Session 1 estimated an individualized inter-stimulus interval (ISI) by testing seven tone-TMS delays (25-300 ms). Session 2 applied PAS at the optimal ISI. Corticospinal excitability was assessed by motor-evoked potentials (MEPs) from right first dorsal interosseus at baseline and post-intervention. Group comparisons and a stepwise multiple regression with Goldsmiths Musical Sophistication Index (Gold-MSI) subscales evaluated predictors of the PAS effect. ResultsA stepwise multiple regression model selected "Group" and "Active Engagement" (Gold-MSI Factor 1) as independent predictors (F (2,26) = 4.59, p = 0.020, adjusted R2 = 0.204), without interaction: musicians exhibited smaller facilitation than non-musicians, and higher Active Engagement predicted greater facilitation across groups. DiscussionThe lack of facilitation in musicians contrasts with somatosensory PAS reports of enhanced plasticity in experts. A modality-specific ceiling effect may contribute, whereby long-term training optimizes auditory-motor transmission, reducing headroom for facilitation. The association with Active Engagement suggests motivational/reward mechanisms--potentially dopaminergic-- gate responsiveness to auditory-motor PAS. ConclusionUnder this protocol, auditory-motor PAS with instrument tones facilitated corticospinal excitability in non-musicians but not in musicians. Individual differences in Active Engagement predicted facilitation, indicating that both group membership and active musical engagement shape susceptibility to auditory-motor associative plasticity.

neuroscience↗

Developmental Reorganization of Whole-Body Muscle Synergies During Overarm Throwing in Children

Overarm throwing is a uniquely human skill that requires precise whole-body coordination. Although throwing behavior emerges early in childhood, the neuromuscular mechanisms that support its development remain poorly characterized. Here, we provide novel evidence for the developmental reorganization of whole-body muscle synergies during maximum-effort throwing in preschool-aged (PS) and school-aged (SA) children. Electromyography was recorded from 16 muscles, and non-negative matrix factorization was applied to extract low-dimensional coordination modules (muscle synergies). We compared ball speed, number of synergies, synergy structure, and temporal consistency between groups. Ball speed was significantly higher in SA than PS (33.6 {+/-} 10.2 vs. 21.4 {+/-} 6.2 km/h, p < 0.05), reflecting improved performance. Yet, the number of synergies did not differ (PS: 6.0 {+/-} 1.1; SA: 6.4 {+/-} 1.3, p > 0.05), suggesting that the dimensionality of coordination is largely established by the preschool years. Instead, developmental improvements were driven by structural and temporal reorganization: trunk- and upper-limb synergies merged into a single module in SA, reflecting improved postural integration, while a bilateral soleus-dominant synergy fractionated into lateralized modules, reflecting increased lower-limb specialization. Moreover, the temporal variability of synergy activation was reduced in SA (p < 0.01), indicating that movement sequences became more precise and stable with development. These findings reveal that early gains in throwing arise not from expanding synergy number but from reorganizing their structure and sharpening temporal coordination, offering mechanistic insight into how complex whole-body skills are refined during childhood. Significance StatementThrowing is a hallmark of human motor behavior, requiring precise sequencing of whole-body muscle activity. Yet how children develop this ability has remained unclear. By applying muscle synergy analysis to electromyographic recordings of preschool and school-aged children performing maximum-effort throws, we found that improvements in performance were not due to an increase in synergy number but rather to structural reorganization and greater temporal precision. Specifically, trunk and upper-limb modules merged, lower-limb modules fractionated, and activation timing became more consistent. These results identify merging and fractionation as complementary mechanisms supporting developmental refinement of motor skills. More broadly, they provide a mechanistic framework for understanding how complex whole-body actions are acquired and offer markers for pediatric training and rehabilitation strategies.

neuroscience↗

Modulation of cortico-muscular coupling associated with split-belt locomotor adaptation

Humans can adjust their walking patterns according to the demands of their internal and external environments, referred to as locomotor adaptation. Although significant functional coupling (i.e. cortico-muscular coherence [CMC]) has been shown between cortical and lower-limb muscle activity during steady-state walking, little is known about CMC in locomotor adaptation. Therefore, we investigated the adaptation-dependent modulation of the CMC between the sensorimotor region and the tibialis anterior muscle using a split-belt locomotor adaptation paradigm that can impose an asymmetric perturbation. We hypothesized that the CMC would temporarily decrease after exposure to the asymmetric perturbation and removal of the perturbation because of a mismatch between the predicted and actual sensory feedback. We also hypothesized that the CMC would increase as adaptation and de-adaptation to perturbation progressed because the motor system could become able to predict sensory feedback. Our findings revealed that the CMC temporarily decreased after exposure to and removal of the perturbation. Moreover, the CMC increased with adaptation and de-adaptation to perturbation. Although these results depend on the leg, frequency bands, and gait phases, they partially support our hypothesis. These findings suggest that flexible updating of cortico-muscular coupling in the motor system is a key mechanism underlying locomotor adaptation in humans. The results from our study on healthy young individuals contribute to the understanding of neuromuscular control of gait and provide valuable insight for optimising gait rehabilitation. Key pointsO_LILocomotor adaptation plays a crucial role in our daily activities and gait rehabilitation. C_LIO_LIAlthough knowledge regarding the brain and muscle activities associated with locomotor adaptation has been accumulated, little is known about the functional coupling of the brain and muscle activities. C_LIO_LIUsing high-density EEG and lower limb EMG, we demonstrated the modulation of cortico-muscular coherence between the sensorimotor region and the tibialis anterior muscle with adaptation and de-adaptation during a split-belt treadmill walking paradigm. C_LIO_LIOur findings suggest that flexible updating of cortico-muscular coupling in the motor system underlies locomotor adaptation in humans. C_LIO_LIUnderstanding the human brains control of muscles during split-belt locomotor adaptation will deepen our knowledge of neuromuscular control of gait and provide valuable insights for gait rehabilitation. C_LI

neuroscience↗

Accurate localization of cortical and subcortical sources of M/EEG signals by a convolutional neural network with a realistic head conductivity model: Validation with M/EEG simulation, evoked potentials, and invasive recordings

While electroencephalography (EEG) and magnetoencephalography (MEG) are well-established non-invasive methods in neuroscience and clinical medicine, they suffer from low spatial resolution. Particularly challenging is the accurate localization of subcortical sources of M/EEG, which remains a subject of debate. To address this issue, we propose a four-layered convolutional neural network (4LCNN) designed to precisely locate both cortical and subcortical source activity underlying M/EEG signals. The 4LCNN was trained using a vast dataset generated by forward M/EEG simulations based on a realistic head volume conductor model. The 4LCNN implicitly learns the characteristics of M/EEG and their sources from the training data without need for explicitly formulating and fine-tuning optimal priors, a common challenge in conventional M/EEG source imaging techniques. We evaluated the efficacy of the 4LCNN model on a validation dataset comprising forward M/EEG simulations and two types of real experimental data from humans: 1) somatosensory evoked potentials recorded by EEG, and 2) simultaneous recordings from invasive electrodes implanted in the brain and MEG signals. Our results demonstrate that the 4LCNN provides robust and superior estimation accuracy compared to conventional M/EEG source imaging methods, aligning well with established neuroscience knowledge. Notably, the accuracy of the subcortical regions was as accurate as that of the cortical regions. The 4LCNN method, as a data-driven approach, enables accurate source localization of M/EEG signals, including in subcortical regions, suggesting future contributions to various research endeavors such as contributions to the clinical diagnosis, understanding of the pathophysiology of various neuronal diseases and basic brain functions.

neuroscience↗

Neuromechanical Justification of Lower-Limb Functional Tests for a Return to Running: A Muscle Coordination Analysis

IntroductionThis study aimed to explore the shared muscle synergies between running and functional tests that are commonly used when considering the return to running (RTR) after sports-related injuries. We hypothesized that shared muscle synergies would differ among tasks, providing insights into prioritizing functional tests in the context of RTR. MethodsTen healthy male participants were recruited to perform running and 9 functional tasks and their 16 lower limb and trunk muscle activities were recorded using electromyography (EMG). Non-negative matrix factorization (NMF) was applied to the collected EMG data to explore shared muscle synergies between running and the functional tasks. We compared the percentages of shared synergies and temporal patterns between running and each functional test. ResultsAlthough all functional tests exhibited shared muscle synergies with running, the walk (75% [40%-100%]), single leg hops with 30% of maximum distance (SLH30) (60% [20%-100%]), and stepup (63% [0%-100%]) tasks displayed significantly higher percentages of shared synergies compared to other tests. However, significant differences in temporal patternss were observed between running and all functional tasks, indicating varying activation profiles of shared muscle synergies. ConclusionAlthough all functional tests shared muscle synergies with running, variations in the degree of shared synergies and temporal patterns imply that walking, SLH30, and step-up tests may be the most beneficial in predicting running behavior post-ACL injuries. However, functional tests cannot fully replicate running dynamics, suggesting the need for a careful interpretation when assessing readiness for RTR.

neuroscience↗

A specific mesh-like organization of human septin octameric complex drives membrane reshaping and curvature sensitivity

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane, we have used a combination of methods to assay their ultrastructural organization, their curvature sensitivity as well as their role in membrane reshaping. In contrast to budding yeast septins, on membranes, human septins systematically organize into a two-layered mesh of orthogonal filaments instead of generating parallel sheets of filaments observed for budding yeast septins. This peculiar mesh organization is curvature sensitive and drives membrane reshaping as well. The observed membrane deformations together with the filamentous organization are recapitulated in a coarsegrained computed simulation to understand their mechanisms. Our results highlight the specificity of animal septins as opposed to fungal proteins.

biophysics↗

Fear in action: Fear conditioning and alleviation through body movements

Acquisition of fear memories enhances survival especially when the memories guide defensive movements to minimize harm. Accordingly, fear memories and body movements have tight relationships in animals: Fear memory acquisition results in adapting reactive defense movements, while training active defense movements to avoid threat reduces fear memory. However, evidence in humans is scarce because their movements are typically marginalized in experiments. Here, we tracked participants whole-body motions while they underwent fear conditioning in a virtual 3D space. First, representational similarity analysis of body motions revealed that participants obtained distinct spatiotemporal movement patterns through fear conditioning. Second, subsequent training to actively avoid threats with naturalistic defensive actions led to a long-term (24 hrs) reduction of physiological and embodied conditioned responses, while extinction or vicarious training only transiently reduced the responses followed by their spontaneous return. Together, our results highlight the intrinsic role of body movements in human fear memory functions, suggesting the potential for improving fear memory interventions through embodiment.

neuroscience↗

Firing behavior of single motor neurons of the tibialis anterior in human walking as non-invasively revealed by HDsEMG decomposition

Investigation of the firing behavior of spinal motor neurons (MNs) provides essential neuromuscular control information because MNs form the "final common pathway" in motor control. The MNs activated during human infants leg movements and rodent locomotion, mainly controlled by the spinal central pattern generator (CPG), show highly synchronous firing. In addition to spinal CPGs, the cerebral cortex is involved in neuromuscular control during walking in human adults. Thus, MN firing behavior during adult walking is expected to be similar to that of infants and rodents and has some unique features. Recent technical advances allow non-invasive investigation of MN firing by high-density surface electromyogram (HDsEMG) decomposition. Therefore, we investigated the MN firing behavior of the tibialis anterior muscle during walking by HDsEMG decomposition. We found motor unit recruitment modulation compared with steady isometric contractions, doublet firings, and gait phase-specific firings during walking. We also found high MN synchronization during walking over a wide range of frequencies, probably including cortical and spinal CPG-related components. The amount of MN synchronization was modulated between the gait phases and motor tasks. These results suggest that the central nervous system, including the spinal CPG and cerebral cortex, flexibly controls MN firing to generate appropriate muscle force during human walking. In addition to revealing the neural control mechanisms of walking, our data demonstrate the feasibility of non-invasive investigation of MNs during walking, which will open new frontiers for the study of neuromuscular function in medical and exercise sciences.

neuroscience↗

Flexible recruitments of fundamental muscle synergies in the trunk and lower limbs for highly variable movements and postures

The extent to which muscle synergies represent the neural control of human behavior remains unknown. Here, we tested whether certain sets of muscle synergies that are fundamentally necessary across behaviors exist. We measured the electromyographic activities of 26 muscles including bilateral trunk and lower limb muscles during 24 locomotion, dynamic and static stability tasks, and extracted the muscle synergies using non-negative matrix factorization. Our results showed that 13 muscle synergies that may have unique functional roles accounted for almost all 24 tasks by combinations of single and/or merging of synergies. Therefore, our results may support the notion of the low dimensionality in motor outputs, in which the central nervous system flexibly recruits fundamental muscle synergies to execute diverse human behaviors. Further studies using manipulations of the central nervous system and/or neural recording are required the neural representation with such fundamental components of muscle synergies.

neuroscience↗

Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimers disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

neuroscience↗

Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms

Septin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9. Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9 thus not recapitulating its native assembly into hetero-octameric complexes. We established a protocol that enabled the first-time isolation of recombinant human septin octamers containing distinct SEPT9 isoforms. A combination of biochemical and biophysical assays confirmed the octameric nature of the isolated complexes in solution. Reconstitution studies showed that octamers with either a long or a short SEPT9 isoform form filament assemblies, and can directly bind and cross-link actin filaments, raising the possibility that septin-decorated actin structures in cells reflect direct actin-septin interactions. Recombinant SEPT9-containing octamers will make it possible to design cell-free assays to dissect the complex interactions of septins with cell membranes and the actin/microtubule cytoskeleton. SummaryHuman septins in cells form hetero-octameric complexes containing the ubiquitously expressed SEPT9. Iv et al. describe the first-time isolation of recombinant human septin octamers with distinct SEPT9 isoforms. Reconstitution studies show that octamers with either a long or a short SEPT9 isoform form higher-order filament assemblies and directly bind and cross-link actin filaments.

cell biology↗

Neural decoding of gait phase information during motor imagery and improvement of the decoding accuracy by concurrent action observation

Brain decoding of motor imagery (MI) is crucial for the control of neuroprosthesis, and it provides insights into the underlying neural mechanisms. Walking consists of stance and swing phases, which are associated with different biomechanical and neural control features. However, previous studies on the decoding of the MI of walking focused on the classification of more simple information (e.g., walk and rest). Here, we investigated the feasibility of electroencephalogram (EEG) decoding of the two gait phases during the MI of walking and whether the combined use of MI and action observation (AO) would improve decoding accuracy. We demonstrated that the stance and swing phases could be decoded from EEGs during AO or MI alone. Additionally, the combined use of MI and AO improved decoding accuracy. The decoding models indicated that the improved decoding accuracy following the combined use of MI and AO was facilitated by the additional information resulting from the concurrent cortical activations by multiple regions associated with MI and AO. This study is the first to show that decoding the stance versus swing phases during MI is feasible. The current findings provide fundamental knowledge for neuroprosthetic design and gait rehabilitation, and they expand our understanding of the neural activity underlying AO, MI, and AO+MI of walking. Significance StatementBrain decoding of detailed gait-related information during motor imagery (MI) is important for brain-computer interfaces (BCIs) for gait rehabilitation. However, previous knowledge on decoding the motor imagery of gait is limited to simple information (e.g., the classification of "walking" and "rest"). Here, we demonstrated the feasibility of EEG decoding of the two gait phases during MI. We also demonstrated that the combined use of MI and action observation (AO) improves decoding accuracy, which is facilitated by the concurrent and synergistic involvement of the cortical activations by multiple regions for MI and AO. These findings extend the current understanding of neural activity and the combined effects of AO and MI and provide a basis for developing effective techniques for walking rehabilitation.

neuroscience↗