Journal of Neurophysiology

Motor skills such as bicycle riding are considered robust and transferable across bicycle types. However, when the steering direction is inverted (reversed bicycle) control is disrupted to the extent that the bicycle cannot be ridden. With sufficient practice, the reversed bicycle can be learned, but this learning appears to produce impairment of normal bicycle riding suggesting modification of this long-established motor memory. Here we investigate the learning process of riding a reversed bicycle over four days of practice, while repeatedly assessing normal bicycle performance to measure any potential interference. Introduction of the reversed bicycle disrupted predictive control, reflected in a consistently increased time lag in the steering-roll coupling during reversed bicycle trials. This increase in delay suggests that predictive behavior in normal bicycle riding cannot be transferred to the reversed bicycle. With training, some participants successfully learned to ride the reversed bicycle by gradually reorganizing this coupling, whereas others failed to acquire this inverted coupling. Notably, even short-term exposure to the reversed bicycle interfered with normal bicycle riding, reducing distance ridden and increasing variability in steering rate. Together, we show that even a highly practiced whole-body motor skill is susceptible to rapid interference when control dynamics are altered.

Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1G93A mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1G93A mice modulate excitability differently than wild type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and/or synaptic inputs in SOD1G93A versus wild type motoneurons. We identified a significant genotype x treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1G93A motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=52 SRC="FIGDIR/small/725609v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@25f125org.highwire.dtl.DTLVardef@faf2c9org.highwire.dtl.DTLVardef@15993a8org.highwire.dtl.DTLVardef@1ed006a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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

Anticipatory postural adjustments (APAs) scale with velocity of approaching objects, with scaling magnitude depending on whether the moving object is actively foveated and tracked, processed through fixated peripheral vision, or processed through fixated central vision. Aging preferentially degrades the magnocellular pathway underlying peripheral motion processing while sparing the extraretinal signals available during smooth pursuit. We therefore asked whether the effect of aging on velocity-dependent APA scaling differs across these three visual pathways. Eighteen young and eighteen older adults stopped a virtual object approaching at four velocities (15-33 cm/s) under three gaze conditions: active foveation via smooth pursuit, central fixation, and peripheral fixation. We measured peak anticipatory force, rate of force development, and time to contact at force onset. Despite reduced smooth pursuit gain in older adults, velocity-dependent scaling was equivalent between age groups during active foveation, and minimal in both groups during central fixation. Critically, young adults scaled force rate during peripheral fixation nearly as steeply as during active foveation, whereas older adults slope was significantly lower -- a difference not observed during the other gaze conditions. Older adults achieved comparable peak force by initiating responses earlier. These results establish that age-related decline in anticipatory motor control is pathway-specific: aging selectively impairs peripheral motion processing for APAs, while extraretinal mechanisms remain capable of sustaining velocity-dependent scaling. More broadly, peripheral motion processing emerges as a candidate physiological locus of age-related postural vulnerability, raising the question of whether magnocellular-targeted training can restore APA scaling in older adults. Key PointsO_LIYoung and older adults stopped virtual objects under three visual conditions: active foveation via smooth pursuit eye movements, and stationary gaze with the object moving through either central or peripheral vision. C_LIO_LIVelocity-dependent force rate scaling was preserved during active foveation in both age groups, minimal during fixated central vision in both age groups, and selectively impaired in older adults during fixated peripheral vision. C_LIO_LIWe found an age-induced vulnerability in peripheral visual motion processing for anticipatory posture stabilization. C_LI

Sympathetic preganglionic neurons (SPNs) distribute signals widely across paravertebral ganglia, yet the reliability of spike propagation along their predominantly unmyelinated axons remains poorly defined. We examined temperature- and activity-dependent modulation of SPN axonal conduction using an ex vivo adult mouse thoracic sympathetic chain preparation. Population compound action potentials (CAPs) were evoked by supramaximal stimulation of T10 ventral roots and recorded from branching axons in interganglionic compared to unbranching axons in the splanchnic nerve. At physiological temperature (36{degrees}C), scaled CAP magnitude was reduced by [~]50% relative to 22{degrees}C, with preferential loss of slower-conducting axonal components. These reductions are consistent with substantial temperature-dependent decreases in effective axonal recruitment, likely reflecting conduction failure in a large fraction of SPNs. Losses were more pronounced in interganglionic pathways, suggesting increased vulnerability in branching projections. To assess activity-dependent effects, stimuli were delivered at 1, 5, and 20 Hz with focus on 5 and 20 Hz stimulus trains (20s duration). The overall time-course of train-evoked depression was similar across temperatures; however, the underlying axonal populations differed. At 22{degrees}C, slower-conducting axons exhibited marked frequency-dependent depression, whereas at 36{degrees}C the remaining faster-conducting axons displayed facilitation, particularly at 20 Hz. Slower-conducting responses also showed post-train potentiation at physiological temperature. These findings indicate that SPN axonal conduction is not uniformly reliable and is strongly modulated by temperature and activation history. Preferential vulnerability of slow-conducting, likely small-diameter and branching axons identifies axonal conduction as a physiologically regulated site of gain control in sympathetic output.

The short-latency stretch reflex (SLR) is the fastest sensorimotor response in human limbs. The spinal SLR is traditionally viewed as automatic and resistant to rapid plasticity, while adaptive feedback is often attributed to transcortical mechanisms underlying the long-latency reflex. Using high-density surface electromyography (64-channel arrays) from the pectoralis major and posterior deltoid during an instructed-delay reaching task, we probed reflex gains with brief perturbations delivered during action preparation. Pre-perturbation muscle activity showed no systematic goal-directed change. After task familiarization and with sufficient preparation time, SLR gains decreased progressively (logarithmically) with experience when the planned movement was expected to stretch the homonymous muscle. This tuning occurred both with and without agonist muscle pre-loading and predicted the observed improvements in reaching performance. Early transcortical responses showed comparable tuning across load conditions. Our study shows that spinal feedback circuits can progressively adapt within a single session to support the performance of goal-directed movements. HighlightsO_LIThe short-latency stretch reflex adapts rapidly with experience in planned reaching C_LIO_LISpinal reflex tuning occurs with and without agonist muscle pre-loading C_LIO_LIReflex tuning evolves logarithmically and predicts reaching performance C_LIO_LIEarly transcortical reflex gains show comparable experience-dependent tuning C_LI

Interlimb skill generalization, defined as the transfer of a newly learned skill from the trained to the untrained limb, represents a fundamental aspect of human motor behavior with significant implications for rehabilitation and athletic training. Skill generalization is influenced by processes that drive learning and interact with the newly acquired memory. For instance, in our recent work, we reported that performing a secondary, cognitively demanding task immediately after a short skill-training session impaired skill generalization when the untrained arm was tested 24-hour later. This suggests that working memory (WM) interacts with the early stage of skill memory consolidation processes and thereby impacts skill generalization. Motivated by this finding, in the current study, we investigate how WM interacts with reactivated skill memory and its subsequent impact on skill generalization, tested 24 or 48-hour post skill training. We recruited right-handed young participants (n=95) who performed a fast, accurate reaching task with their dominant right arm during a short training session (50 trials) on Day-1. After 24-hour on Day-2, depending on the group type, participants had a brief skill reactivation session (10 trials or no reactivation) and then performed the WM task (or a control task) with their right arm. Interlimb generalization to the untrained left arm was assessed either immediately after the WM/control task on Day-2 or after a 24-hour gap on Day-3. We found that, engaging in the WM task (compared to the control task) after skill reactivation on Day-2 enhanced immediate generalization. Conversely, when generalization was tested 24-hour later on Day-3, the same WM engagement impaired skill generalization. These findings demonstrate that WM engagement during the post-reactivation phase has a time-dependent influence on interlimb generalization. WM can facilitate immediate generalization, possibly by sustaining neural processes that promote skill memory generalization across effectors. However, when a 24-hour time gap is introduced, generalization is disrupted following WM engagement, possibly because of interference between underlying neural processes involved in WM and reactivation-induced (re)consolidation of the skill memory. This study highlights the delicate interplay among WM, motor memory reactivation dynamics, and skill generalization and suggests a time-dependent interplay of neural processes critical for optimizing outcomes in motor learning and clinical rehabilitation protocols.

Internal forward models predict the sensory consequences of motor commands; however, whether the anticipated availability of post-action feedback contributes to the precision of the action itself remains unknown. We manipulated the predictability of post-release visual occlusion in skilled basketball players. Participants performed three-point shots while wearing liquid-crystal shutter goggles. The study tested three conditions: a no-occlusion baseline, certain-occlusion condition in which players knew that their vision would be occluded at ball release in every trial, and random-occlusion condition in which they could not predict whether an occlusion would occur. Shooting accuracy declined in the certain-occlusion condition relative to the no-occlusion condition (49.2% vs 41.7%). The random-occlusion condition did not differ from the baseline (46.1%). Within the random condition, the accuracy in occluded trials were virtually identical to that in non-occluded trials (46.6% vs 46.2%), even though the immediate visual occlusion was the same as in the certain-occlusion condition. These results demonstrate that it is not the absence of post-action information per se that disrupts motor execution, but the prior certainty that action consequences will be unavailable. We interpret this finding as a prospective influence of anticipated consequence loss, whereby motor execution depends on whether the prediction-outcome loop remains closable.

Electrical transmission is mediated by intercellular channels that cluster into structures known as gap junctions (GJ). In vertebrates, GJ channels are encoded by the gene family of connexin (Cx) proteins that assemble as hexamers, termed hemichannels, in the pre- and postsynaptic membranes, and that subsequently dock to form GJ channels. Auditory contacts on the fish Mauthner cells serve as model to study the properties and organization of vertebrate electrical synapses. Electrical transmission at these synapses is mediated by multiple co-existing GJs at which the presence of intercellular channels is regulated by a molecular scaffold. Zebrafish contain four homologs of the neuronal Cx36: Cx35.5 and Cx35.1 (gjd2a and b, respectively), and Cx34.1 and Cx34.7 (gjd1a and b). Cx mutations suggested that GJs are formed by heterotypic channels made of presynaptic Cx35.5 and postsynaptic Cx34.1. Using transgenic fish in which Cxs were tagged, we found that a second Cx, Cx34.7, is present together with Cx34.1 on the postsynaptic side at some but not all GJs at these terminals. When exogenously expressed, both Cx34.1 and Cx34.7 formed heterotypic functional channels with Cx35.5, each with substantially different voltage-dependent properties, indicating they can serve differential functions. However, we previously demonstrated that electrical transmission is lost in Cx34.1 but not Cx34.7 null mutants, suggesting that Cx34.7 cannot compensate for the loss of Cx34, despite the intrinsic ability of Cx34.1 and Cx34.7 to create functional channels. The findings reveal an unanticipated functional organization in the electrical synapse, where Cx34.1 is obligatory and Cx34.7 accessory, roles that appear to be defined by the postsynaptic molecular scaffold, with two postsynaptic Cxs possibly assembling under specific functional contexts. Thus, our results indicate that electrical synapses share an organizational motif with chemical synapses, akin to how they combine postsynaptic receptor types to modify synaptic function.

Clinical deafferentation underscores the fundamental role of proprioception in motor control, but chronic sensory loss also drives long-term compensatory strategies that complicate mechanistic inference. Because proprioceptive reliability is difficult to manipulate experimentally, its contribution to skilled control remains unclear. Virtual reality (VR) with controlled visuo-proprioceptive offsets provides a promising model of proprioceptive unreliability that induces sensory reweighting toward vision during conflict. This VR-offset framework has advanced our understanding of vision-dominant control under proprioceptive unreliability in reaching tasks. It remains unknown how the motor system responds to proprioceptive unreliability during skilled object manipulation. Unlike reaching, manipulation requires anticipatory force/torque control that accounts for trial-to-trial variability in digit position; these policies are learned within a few trials, yet changes in object dynamics produce anterograde interference that increases with greater repetition before the dynamics switch. Although vision, tactile cues, and prior experience support these features, the role of proprioceptive reliability remains unresolved. Hybrid-VR, which pairs real object interaction with virtual visual feedback, offers a way to address this gap. Before introducing offsets, we must establish that hybrid-VR without offsets reproduces the hallmark behaviors highlighted above. Here, we compared real-world object manipulation with hybrid-VR object manipulation where participants (N = 15) lifted and stabilized an object with an asymmetric mass distribution. Across real-world and hybrid-VR conditions, the rate of anticipatory force control, trial-to-trial position-force adjustment, and switch-related interference were indistinguishable. These results demonstrate that hybrid-VR reproduces hallmark features of dexterous manipulation, providing a foundation for future studies isolating proprioceptive reliability. NEW AND NOTEWORTHYHybrid virtual reality (VR), combining a real object interaction with immersive VR, preserves core features of real-world object manipulation, including rapid anticipatory force learning, trial-by-trial coordination of digit position and force, and repetition-induced interference. This hybrid-VR approach maintains natural sensorimotor control while allowing for controlled manipulation of visual information. This validated framework provides a new tool to isolate how proprioceptive reliability shapes skilled object manipulation.

Cybersickness is a major barrier to the widespread adoption of virtual reality (VR), yet its underlying neurophysiological mechanisms remain poorly understood. This study investigated the relationship between vestibulomotor weighting and cybersickness. Vestibulomotor weighting was quantified using electrical vestibular stimulation (EVS), with coherence and gain between the EVS input and medial-lateral center-of-pressure (ML-CoP) responses indexing the contribution of vestibular input to postural control. Thirty-eight healthy young adults (females n=21, males n=17) completed a standing VR rollercoaster task while receiving continuous stochastic EVS (0-25 Hz; {+/-}4.5 mA), with ML-CoP responses recorded using a force plate. Cybersickness was assessed using the Fast Motion Sickness Scale (FMS) and Simulator Sickness Questionnaire, and participants were classified as non-sick (FMS < 5), medium-sick (FMS [&ge;] 5), or high-sick (terminated the VR exposure early due to intolerance). Baseline EVS-ML-CoP coherence across 2.5-8 Hz was significantly greater in high-sick than in non-sick participants, indicating elevated vestibulomotor weighting in individuals who developed symptoms. During VR exposure, coherence declined over time in symptomatic groups (mean slope = -0.0027 for medium-sick), whereas non-sick participants maintained consistently low coherence (mean slope = -0.0005). Despite this reduction in vestibular coupling, postural sway increased in the high-sick group relative to the medium-and non-sick groups (+29% vs. -7% and -30% change in ML-CoP RMS, respectively), while vestibular-evoked response amplitude decreased (gain reduced by 64% across 2.5-3.5 Hz). These findings indicate that greater baseline vestibulomotor weighting was associated with increased susceptibility to cybersickness, whereas reductions in vestibular contributions during VR with EVS reflected adaptive reweighting that was insufficient to prevent instability and symptom progression. Together, the results highlight baseline sensory reliance as a key determinant of cybersickness vulnerability and suggest that reweighting during exposure plays a secondary, mitigating role. New and NoteworthyWe provide the first evidence that baseline vestibulomotor weighting predicts susceptibility to cybersickness in virtual reality and is dynamically reduced during exposure. Using electrical vestibular stimulation, we show that symptomatic individuals begin with greater reliance on vestibular input for postural control and progressively downweight these signals in response to sensory conflict.

Human pointing is often used to test whether dogs extract object-specific information from human communicative cues. However, above-chance responses in standard object-choice tasks do not by themselves distinguish between a referential interpretation, in which the gesture identifies a specific target, and an attentional interpretation, in which it primarily biases behaviour toward a broader spatial region. We addressed this issue using an asymmetric six-cup arrangement designed to separate coarse side guidance from exact cup localisation more clearly than a symmetric multi-cup design. Performance in domestic dogs was analysed using three measures: the probability of reaching the correct side, the probability of choosing the correct cup overall, and the probability of choosing the correct cup conditional on having first reached the correct side. The principal comparison involved three matched trial classes: the symmetric 3-vs-3 condition, 2-vs-4 trials with the baited cup on the 2-cup side, and 2-vs-4 trials with the baited cup on the 4-cup side. Descriptively, pointing trials exceeded matched no-point control trials more clearly for side selection than for overall cup choice. The clearest condition effect was observed at the level of side guidance. Dogs were most likely to reach the correct side when the baited cup was located on the 4-cup side of the unequal arrangement. Mixed-effects models confirmed a reliable group effect for side accuracy, whereas overall cup accuracy showed only a weaker and less robust condition effect, and within-side localisation revealed no reliable group difference once condition-specific chance baselines were taken into account. A complementary generative model comparison converged on the same conclusion: a referential-only model fit poorly, an attention-only model captured most of the grouped outcome structure, and a combined model yielded only a modest improvement. Dog point-following is therefore best understood as a layered process dominated by attentional guidance, with only limited additional target-specific localisation.

Sympathetic preganglionic neurons (SPNs) provide the final pathway through which the central nervous system regulates autonomic function. SPN axons projecting to paravertebral sympathetic chain ganglia branch extensively and diverge across multiple segments, enabling amplification of central sympathetic commands through extensive postganglionic neuronal populations. Spike propagation along these projections has generally been assumed to occur reliably. However, most SPN axons are extremely small unmyelinated fibers, a structural feature predicted to reduce the safety factor for spike propagation. Using an isolated mouse thoracic sympathetic chain preparation, we combined anatomical tracing with multi-site compound action potential recordings to assess conduction across SPN axons. Neurobiotin labeling revealed widespread rostrocaudal divergence through interganglionic nerves, while axon measurements confirmed that most SPN axons are small unmyelinated fibers. Across preparations, supramaximal recruitment of SPNs revealed substantial intertrial variability in compound responses, indicating frequent conduction failures. Failures were most prominent in slow-conducting axons and occurred in both branching interganglionic pathways and the unbranching axons within the splanchnic nerve. During repetitive activation, frequency dependent depression was observed at 1, 5 and 10Hz, but only slow-conducting branching axons exhibited pronounced depression. Overall, these findings indicate that spike propagation in SPN axons may operate probabilistically rather than deterministically, with reliability strongly dependent on axonal subtype and recent activity history. We conclude that axonal conduction variability constitutes an intrinsic and dynamically regulated mechanism that shapes sympathetic output. By varying the recruitment of postganglionic populations, unreliable spike propagation in SPN axons introduces a previously unrecognized presynaptic gain-control mechanism, operating independently of central spike generation to modulate sympathetic output. SIGNIFICANCESympathetic preganglionic neurons provide the final pathway through which the central nervous system controls end-organs. These neurons project through the sympathetic chain where their axons branch extensively to recruit more numerous paravertebral postganglionic neurons. Spike propagation along these projections has generally been assumed to occur reliably. Here we show that this assumption is incorrect. Using anatomical tracing and electrophysiological recordings in mouse sympathetic chain preparations, we demonstrate that spike conduction in sympathetic preganglionic axons is frequently variable and prone to failure, particularly in the slowest-conducting unmyelinated fibers. Conduction variability was preferentially enhanced in branching axonal pathways during repetitive activation. These findings reveal that axonal conduction reliability represents an important presynaptic mechanism regulating the magnitude and variability of sympathetic output.

Calibration of sound localization behavior in species with mobile eyes requires not only accurate visual input but also accurate oculomotor signals across the lifespan. The recent discovery of eye movement-related eardrum oscillations suggest that oculomotor signals may be incorporated into auditory processing at the level of the ear. One inference of this discovery is that individual variation in such signals might be correlated with individual variation in sound localization accuracy. Here, we tested this hypothesis in humans with normal hearing. We discovered that there is considerable variation in the accuracy of sound localization (here, saccades to sounds) even in normal individuals: median horizontal errors ranged from 2-6{degrees}, and median vertical errors could be as large as 36{degrees}. We separated the subject pool into groups with "good" performance (median vectorial error < 8{degrees}) vs "poor" performance (median vectorial error > 10{degrees}) and evaluated their respective EMREOs. The EMREOs differed across the two groups in both horizontal and vertical dimensions, in how saccade amplitude vs. initial eye position was encoded, and across time with respect to the saccade. These results are consistent with the interpretation that EMREOs are associated with underlying processes that ensure the accuracy of sound localization. HIGHLIGHTSO_LIThe accuracy of eye movements to look at sounds varied across individuals, with median errors spanning a greater than 10-fold range. This range is surprising given that the participants passed screening for normal hearing. C_LIO_LI"Good" vs "poor" sound localizers exhibited differences in their eye movement-related eardrum oscillations (EMREOs) C_LIO_LIEMREOs differed in both horizontal and vertical sensitivity, for both saccade amplitude and initial eye position, and the differences varied in timing with respect to saccade onset. C_LIO_LIWe interpret the results under the theory that poor sound localization may be a consequence of poor eye movement encoding, without which linking visual and auditory space is likely inaccurate. C_LI

Motoneuron subtypes exhibit distinct firing properties that are critical for the graded control of muscle force. A key determinant of these differences is the medium afterhyperpolarization (mAHP), which shapes discharge rate and firing gain. While subtype-specific variation in mAHP properties has traditionally been attributed to differences in small-conductance calcium-activated potassium (SK) channel expression, emerging evidence suggests that additional conductances may contribute. Here, we investigated the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in regulating the mAHP and excitability of mouse spinal motoneurons during postnatal development. Using whole-cell patch-clamp recordings, we show that, by the onset of the third postnatal week, an h current (Ih) is active at resting potential in fast motoneurons and is correlated with the amplitude of the mAHP. Pharmacological blockade of HCN channels with ZD7288 increased mAHP amplitude in fast but not slow motoneurons, without affecting mAHP duration, indicating a subtype-specific contribution to mAHP amplitude. In line with the mAHP regulating firing gain, ZD7288 also reduced firing gain in fast but not slow motoneurons. These findings support a contribution of HCN channel activity to the regulation of mAHP amplitude and firing gain in fast motoneurons, highlighting a potential interaction between Ih and SK channel-dependent mechanisms in shaping motoneuron excitability. Key PointsO_LIThe amplitude of the medium afterhyperpolarization (mAHP) is negatively correlated with h-current (Ih) amplitude measured near resting potential in mouse lumbar motoneurons. C_LIO_LIPharmacological blockade of HCN channels selectively increases mAHP amplitude in fast, delayed firing alpha motoneurons, with no effect observed in slow, immediate firing alpha motoneurons. C_LIO_LIInhibition of HCN channels reduces firing gain in fast motoneurons, while slow motoneurons remain unaffected. C_LIO_LIHCN channels regulate firing gain in fast motoneurons, at least in part, through modulation of mAHP amplitude. C_LI

Understanding how the brain operates in naturalistic settings requires methods that go beyond conventional repeated-measurement approaches, necessitating the development of single-trial neural activity analysis. Recent advances in machine learning offer new opportunities for analyzing brain electrophysiological signals. Here, we recorded surface electrocorticography (ECoG) and intracranial local field potentials (LFPs) from emotion-related brain regions in a monkey performing a Pavlovian conditioning task, in which sensory cues predicting reward or punishment were presented randomly, followed by the actual unconditioned outcome. We evaluated the performance of two machine learning algorithms, a Convolutional neural network (CNN) model and a Transformer-based model (EEG-Conformer), in classifying raw ECoG/LFP traces. Both models successfully classified valence type during conditioned and unconditioned stimulus presentation. Furthermore, the Transformer achieved significantly superior classification performance compared to the CNN, particularly in multi-state classification including baseline periods. By optimizing the training dataset for the Transformer model, we could detect dynamic fluctuations in emotional valence consistent with task type from continuously evolving ECoG/LFP patterns recorded throughout the task. These results demonstrate the utility of Transformer-based models for decoding emotional valence from neurophysiological signals in non-human primates.

Visual response strength in the primate superior colliculus (SC) has recently been shown to inversely correlate with trial-by-trial saccadic reaction time in a much stronger way than visual response strength in the primary visual cortex (V1). However, for any given visual stimulus onset, populations of neurons in each brain area are concurrently activated, leaving open the question of how V1 visual response strength can predict trial-by-trial saccadic reaction time when multiple simultaneously recorded neurons are taken into account. Using a classic visually-guided saccade task, here we assessed the quality of predicting trial-by-trial saccadic reaction time from the visual response strengths of 1 to 10 simultaneously recorded neurons in each brain area. For each session, we modeled saccadic reaction time as a weighted linear combination of the visual response strengths of N simultaneously recorded neurons. Consistent with the prior work, the visual response strength of a single SC neuron was better than that of a single V1 neuron at predicting reaction time. By adding more simultaneously recorded neurons, the prediction got much better in the SC, but not in V1.Only for 100% contrast dark stimuli (darker in luminance than the surrounding gray background) did V1 show an increase in prediction quality with more simultaneously recorded neurons. This increase, which was still substantially weaker than in the SC, could reflect the preference of V1 neurons for dark contrasts. These results suggest that despite qualitative similarities between SC and V1 visual responses, SC visual responses are functionally reformatted from their V1 counterparts. SignificanceThe superior colliculus (SC) is an important sensory-motor structure for controlling eye movements, and it receives a significant portion of its inputs directly from the primary visual cortex (V1). Despite this, SC visual responses are much better correlated with trial-by-trial variability in saccadic eye movement timing than V1 visual responses, and this effect is strongly amplified when considering simultaneously recorded neurons. Thus, SC and V1 visual responses serve fundamentally different functions from a motor perspective.

Strikingly, highly trained athletes engaged in vertiginous activities (e.g., dance and slacklining) and patients with bilateral vestibular loss show a similar pattern of neural plasticity, likely resulting from reduced vestibular sensory processes. However, unlike patients, these athletes show no balance impairments, quite the opposite. This suggests that the attenuation of vestibular processing represents an adaptive recalibration to excessive vestibular stimulation rather than a sign of dysfunction. Concurrently, tactile processing increases as vestibular processing attenuates. Our findings indicate that effective adaptation extends beyond simple tactile compensation: it involves a strengthened tactile-brain pathway. Indeed, following unexpected base-of-support translations, the coupling between plantar shear forces (i.e., a proxy of plantar sole tactile afferents) and cortical responses over the somatosensory areas was markedly enhanced in Athletes. Cross-correlation analysis revealed stronger (r = 0.71) and faster (36 ms) tactile-brain coupling in Athletes (n = 25) compared with age- and gender-matched Controls (n = 18). This enhancement occurred within the first 180 ms following translation, that is, during the critical early phase of skin-surface interaction. Notably, artistic swimmers, who undergo intense vestibular stimulation in a weightless underwater environment without balance equilibrium constraints, also exhibit enhanced tactile-brain coupling. This suggests that strengthening the tactile-brain coupling is not merely a byproduct of balance expertise, but rather a broader adaptive response to sustained vestibular stimulation. Multimodal neurons integrating vestibular and somatosensory inputs, such as those in the somatosensory cortex and thalamus, may increase their responsiveness to foot tactile afferents when vestibular inputs become excessive. In such contexts, the somatosensory system may assume a dominant role in providing gravity-related information for balance control.

Musical rhythm is often experienced with a periodic beat, serving as a temporal reference for coordination with the rhythm. Thus far, models of beat processing have mainly relied on representing sensory inputs as patterns of onset timing, with limited consideration of other sensory features. Here, we challenge this view by showing that the internal representation of beat is affected by other temporal features of the stimulus beyond onset timing alone. We recorded electroencephalography (EEG) while participants listened to rhythmic sequences designed to elicit a beat. Across conditions, we manipulated the duration of the tones conveying the rhythms, while keeping all other parameters identical, including overall intensity, speed, and rhythmic pattern structure. Crucially, the beat periodicity was enhanced in neural activity with increased sound duration, even though the beat periodicity was not prominent in the acoustic features, thus ruling out basic sensory confounds. These results demonstrate the preferential role of longer sound durations in fostering temporal scaffolding processes that integrate fast rhythmic inputs into behavior-relevant internal structures such as the beat. More generally, our findings are compatible with a holistic processing account whereby a range of features beyond onset timing may be integrated into a neural representation of rhythm. Graphical Abstract: Fig. 2EEG was recorded while listeners heard rhythmic sequences eliciting a beat. Sound duration (sonic duty cycle) was varied across four conditions while speed, pattern, and intensity stayed constant. Beat-related EEG responses increased with longer sounds, and were enhanced in all conditions compared to auditory nerve model envelopes, which did not show prominent energy at the beat periodicity, ruling out sensory confounds. Results support holistic rhythm processing beyond onset timing alone. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/721298v1_fig2.gif" ALT="Figure 2"> View larger version (27K): org.highwire.dtl.DTLVardef@10a0599org.highwire.dtl.DTLVardef@f5a95forg.highwire.dtl.DTLVardef@42d1ceorg.highwire.dtl.DTLVardef@dc58a7_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO EEG and auditory nerve model output analysis based on magnitude spectrum and autocorrelation. Each row represents a duty cycle condition. The two columns on the left represent the magnitude spectrum-based analysis. The first column represents the group-level averaged magnitude spectra at a pool of fronto-central electrodes, across conditions. Beat-related frequencies are shown in red, and beat-unrelated frequencies are shown in blue. Scalp topographies of the neural activity measured at the average magnitudes of beat-related (in red circle) and unrelated (in blue circle) frequencies are represented as insets. The second column represents the normalized magnitude spectra obtained from the auditory nerve model output for each duty cycle sequence. The two columns on the right represent the autocorrelation-based analysis (for visualization purposes, only a subset of lags from 0 to 2.4 s corresponding to the pattern duration is shown). The first column represents the group-level averaged autocorrelation function measured from the same pool of fronto-central electrodes, across conditions. Beat-related lags are shown in red, and beat-unrelated lags are shown in blue. The second column represents the autocorrelation function of the auditory nerve model output for each duty cycle sequence. C_FIG

Sensory degradation with aging can impair balance control, partly by disrupting visual contributions to self-motion estimation. We investigated how aging affects the control of frontal plane center of mass (CoM) trajectories during walking with exposure to repeated visual perturbations. We hypothesized that aging would increase responses to visual perturbations and decrease adaptation to repeated visual perturbation exposure. We applied three visual perturbations to 14 healthy older (age: 75.0{+/-}2.4) and 16 younger adults (age: 23.4{+/-}3.9) walking on a treadmill: fixating a stationary target with the background moving to the right (MB), tracking a target moving rightward over a stationary background with head rotation (MT-HR), and tracking a moving target with eye movement only (MT-EM). Deviations of CoM position and foot placement due to the visual perturbations were assessed. Over the whole trial, the older adults exhibited larger CoM position variability in MB and MT-HR conditions. During visual perturbation epochs, both age groups deviated in the same direction except MB. In MB, the older adults deviated to an opposite direction after a few perturbation repetitions. Moreover, in MT-HR and MT-EM, the older adults deviated earlier than the younger adults and they deviated more in the MT-HR condition. This indicates that older adults exhibit reduced ability to accurately estimate self-motion through correction by other sensory modalities when exposed to visual perturbations. Over repeated perturbations, the older adults showed decreased CoM deviations in MT-EM, which suggests that they still maintain the capacity to downweight visual information after repeated exposure.