Journal of neurophysiology最新文献

{"title":"Intranasal poly(I:C)-induced inflammation alters olfactory bulb-entorhinal cortex circuit and its coupling to breathing.","authors":"César Alexander Zaa, Ricardo Jair Ramírez-Carreto, Benito Ordaz-Sánchez, Anahí Chavarría, Fernando Peña-Ortega","doi":"10.1152/jn.00129.2026","DOIUrl":"10.1152/jn.00129.2026","url":null,"abstract":"<p><p>The olfactory bulb (OB)-entorhinal cortex (EC) circuit is involved in odor information processing and contextualization, as well as other cognitive processes that require the proper generation of neuronal network activity patterns often synchronized with breathing and affected during rhinitis. Although both the OB and the EC frequently show clear signs of neuroinflammation and neuronal stress in response to a variety of peripheral and central proinflammatory stimuli, the functional state of the OB-EC circuit during experimental rhinitis has not been explored. To fill this gap, we explored the impact of nasal inflammation, induced by the viral mimetic polyinosinic:polycytidylic acid [poly(I:C)], on the circuit composed of the OB and EC by measuring their individual neural network activities and quantifying their functional connectivity in the absence and presence of odors. We also measured the presence of proinflammatory markers in both structures and the animals' olfaction. We found that three daily intranasal poly(I:C) administrations are enough to increase proinflammatory cytokine levels in the OB and EC and to reduce olfactory detection in a novel context. Intranasal poly(I:C)-induced inflammation leads to a reduction in the power of OB and EC neural network activity and diminishes their response to odors. Moreover, poly(I:C)-induced inflammation reduces coupling between the OB and the EC at various frequencies, including those close to the respiratory rhythm. It also reduces the coupling between the EC and breathing, which is not observed in the OB. Taken together, our findings indicate that intranasal viral infection leads to neuroinflammation in the OB-EC circuit, affecting its function and connectivity, as well as its coupling to breathing, which could contribute to the olfactory and cognitive deficits observed in rhinitis.<b>NEW & NOTEWORTHY</b> To understand the olfactory and cognitive deficits observed in viral rhinitis, we described the impact of nasal inflammation, induced by the viral mimetic poly(I:C), on the circuit composed of the olfactory bulb and entorhinal cortex by measuring their individual neural network activities and their functional connectivity in the absence and presence of odors. We also evaluated signs of neuroinflammation in both structures and the animals' olfaction, revealing pathological mechanisms behind neurological manifestations associated with rhinitis.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"643-652"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaze-centered spatial coding of touch on a hand-held tool.","authors":"Lefteris Zografos Themelis, W Pieter Medendorp, Luke E Miller","doi":"10.1152/jn.00165.2025","DOIUrl":"10.1152/jn.00165.2025","url":null,"abstract":"<p><p>Humans possess the remarkable ability to project tactile sensations outside their body and onto a hand-held tool that they are using. Despite nearly a century of research, the computations underlying this projection have not been adequately addressed. In the present study, we used model-driven psychophysics to fill this gap. We hypothesized that tool-based sensory projection involves the remapping of touch from sensory feedback in the hand into an egocentric coordinate system. We first formalized the computational steps underlying tactile remapping. We designed a novel tool-sensing experiment that allowed us to rigorously test this model. In this task, participants contacted an object with a hand-held rod and then judged whether the object was above or below where they were currently looking. This comparison would only be possible if the touch on the tool was projected outside the hand. Crucially, both object location and gaze position varied independently, allowing us to characterize the hand-to-space-to-gaze remapping process. Model-based curve fitting provided strong evidence that all participants in our task projected touch outside their body and into gaze-centered coordinates. Crucially, the resolution of this projection was similar to what has been found for touch on the body. These findings provide the first step toward characterizing the computations underlying the spatial projection of touch on external objects, highlighting the incredible versatility of the sensorimotor system.<b>NEW & NOTEWORTHY</b> Humans possess the remarkable ability to project tactile sensations outside their body and onto a hand-held tool. Despite nearly a century of research, the computations underlying this projection have not been adequately addressed. We combined computational modeling and psychophysics to demonstrate that egocentric tactile remapping underlies tool-based sensory projection. These findings provide the first characterization of the computations underlying the spatial projection of touch on external objects, highlighting the incredible versatility of the sensorimotor system.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"468-473"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromodulatory strategies overcome multiple inevitable impairments of cerebral palsy.","authors":"Susan D Hastings, Hui Zhong, Ken Kijima, Casey Gonnella, Jen Gonnella, Darrin J Lee, Charles Liu, Yury P Gerasimenko, V Reggie Edgerton, Christopher A Johnson","doi":"10.1152/jn.00518.2025","DOIUrl":"10.1152/jn.00518.2025","url":null,"abstract":"<p><p>Cerebral palsy (CP) is traditionally characterized as a disorder of motor impairment; however, growing evidence suggests it reflects broader dysregulation across multiple physiological systems. We present a longitudinal case study examining whether pairing transcutaneous spinal neuromodulation (TSN) with a proprioceptive-derived intervention (PDI) can engage systems-level functional adaptation in an adolescent with CP spastic diplegia, whose progress had plateaued after years of conventional therapy. Across 2 years of the intervention, structured clinical observations revealed progressive and reversible improvements spanning posture, locomotion, fine motor control, speech, vision, hearing, sleep, endurance, executive function, and psychosocial engagement. Motor coordination often changed rapidly with stimulation, autonomic functions evolved over intermediate timescales, and longer-lasting changes consistent with support of physiological capacity and recovery emerged more gradually. The task specificity, state dependence, and reversibility of these effects are consistent with activity-dependent processes guided by enhanced proprioceptive signaling during TSN + PDI. Importantly, these adaptations did not emerge uniformly across domains. These findings support a reconceptualization of CP not solely as an isolated motor disorder, but as a condition of maladaptive multisystem regulation that may be amenable to noninvasive, proprioceptively derived neuromodulatory rehabilitation strategies. Although limited to a single case, this work highlights underappreciated neuroadaptive potential in CP and motivates future controlled studies targeting systems-level recovery.<b>NEW & NOTEWORTHY</b> This 2-year longitudinal case report extends beyond motor outcomes to examine systems-level changes in cerebral palsy (CP). Using combined qualitative and quantitative evidence, we show that pairing transcutaneous spinal neuromodulation with proprioceptive-derived intervention can engage activity-dependent neuroplasticity across multiple physiological domains. Coordinated improvements in motor, autonomic, and cognitive function, with distinct temporal dynamics and reversibility, suggest that enhancing proprioceptive signaling may modulate and improve distributed physiological networks and reveal clinically relevant targets for future study.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"445-458"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Dale never said: multiple incarnations of Dale's law from the birth of pharmacology to modeling brain circuits.","authors":"Gabrielle J Gutierrez, Natasha Baas-Thomas, Eve Marder","doi":"10.1152/jn.00196.2026","DOIUrl":"10.1152/jn.00196.2026","url":null,"abstract":"<p><p>In the first half of the 20th century, Sir Henry Dale played a major role in the development of modern pharmacology. Working with several newly identified biologically active substances and simple bioassays, Dale and his colleagues deduced the existence of specific transmitter and hormone receptors. They developed concepts of agonist and antagonist actions, many years before the receptor proteins responsible for the actions of neurotransmitters were purified and characterized. Dale observed that acetylcholine and epinephrine could evoke either excitatory or inhibitory actions on different target tissues and postulated that these same substances were released in the central nervous system. This was turned by other scientists into the first instantiation of Dale's law, which stated that a given neuron only releases one neurotransmitter. In the second half of the 20th century, it became clear that many neurons synthesize and release many cotransmitters that could elicit postsynaptic actions of variable signs and durations, and that the same neuron could be excitatory at some of its targets and inhibitory at others. Today, the theory community often uses the term \"Dale's Law\" as a short hand for models in which all of the postsynaptic actions of a modeled neuron are exclusively excitatory or inhibitory. Although much can be learned from these models, this constraint should not be considered as a prerequisite for biologically realistic models. Doing so risks overlooking the open questions that have emerged through modern updates to Dale's work.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"702-708"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents.","authors":"Ian Huang, Leandro M Alonso, Eve Marder","doi":"10.1152/jn.00055.2026","DOIUrl":"10.1152/jn.00055.2026","url":null,"abstract":"<p><p>The voltage dependences of ion channels are subject to change as a function of activity and neuromodulatory influences. We study the effects of alterations of the activation and inactivation curves in each of seven voltage-dependence currents in a bursting computational model, in control conditions and in simulated high potassium conditions. We find that modifications of the voltage-dependence of one current can result in changes of the contribution of many or all of the currents in the model neuron to its behavior. We construct two-dimensional maps of the regions of bursting, tonic spiking, or silence as a function of the voltage-dependence of participating currents, in both control and simulated high potassium. Consistent with experimental findings, the position of bursting regimes under the two conditions shows that most bursting neurons lose their bursting behavior in high potassium. The maps show that, in most but not all models, bursting can be recovered in high potassium conditions by shifts in the voltage-dependence of one or more of the neuron's currents. Surprisingly, in many models, shifts in the activation curves of several different currents can recover bursting behavior. Moreover, multiple degenerate bursting models with different maximal conductances can recover function in response to changes in the same ionic current. In some models, coordinated shifts in the voltage-dependence of two or more currents are necessary for recovery of bursting activity. These studies demonstrate that modulation of voltage-dependence can both alter a neuron's activity and contribute to resilience subsequent to perturbation.<b>NEW & NOTEWORTHY</b> We explored the effects of modifying the activation and inactivation curves of currents in a bursting model neuron, in control conditions and in response to depolarizing perturbations. Modifications of the voltage-dependence of one current can result in changes of the contribution of many or all of the currents in the model neuron to its behavior, and can contribute to recovery from perturbations.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"474-489"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute fentanyl toxicity: from opioid-induced to hypoxia-mediated pathophysiology.","authors":"Tristan Lewis, Annick Judenherc-Haouzi, Amanda Reinhardt, Philippe Haouzi","doi":"10.1152/jn.00107.2026","DOIUrl":"10.1152/jn.00107.2026","url":null,"abstract":"<p><p>Fentanyl now accounts for most opioid overdose deaths, yet acute fentanyl toxicity is still primarily understood as respiratory depression. This view is incomplete. Fentanyl produces effects distinct from classical opioids, and looking at breathing control in isolation ignores the physiological mechanisms of O₂ delivery and O₂ sparing following overdose. This review proposes an integrated framework based on the physiology of O₂ delivery (DO₂). Fentanyl lethality results from a mismatch between DO₂ and O₂ consumption (V̇o₂) initiated by three centrally mediated toxicities: <i>1</i>) central apnea and sustained hypoventilation reducing arterial O₂ content; <i>2</i>) skeletal muscle rigidity impairing ventilation and causing hypermetabolism; and <i>3</i>) cardiovascular depression via vagally mediated bradycardia and reduced cardiac output. Fentanyl reduces both determinants of DO₂ while increasing consumption, so the DO₂/V̇o₂ ratio collapses faster than hypoventilation alone predicts. The resulting hypoxia shifts the pathophysiology from opioid-dependent to hypoxia-dependent. Severe hypoxemia inhibits respiratory neurons and impairs myocardial contractility, creating a positive feedback loop no longer responsive to naloxone. Pre-existing ventilatory impairment, polysubstance exposure, and acute lung injury further narrow the recovery margin. Endogenous defenses, including gasping and opioid-resistant respiratory rhythms, may allow recovery if adequate DO₂ is restored in time. Fentanyl lethality is an O₂ crisis requiring therapeutic strategies that address the full DO₂/V̇o₂ mismatch.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"722-734"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid sequential touches complicate whisking-phase analysis in mouse active touch.","authors":"Yuxuan Xu","doi":"10.1152/jn.00211.2026","DOIUrl":"10.1152/jn.00211.2026","url":null,"abstract":"<p><p>In rapid sequences, a fixed counting window can include spikes occurring after a neighboring contact. I reanalyzed 19,675 touches from 41 loose-seal recordings of excitatory layer 4 neurons in the public Hires et al. dataset. Spikes were recounted in windows of 10 to 50 ms around each touch. Counts after touch changed little with the preceding interval. Subtracting the rate before touch produced positive interval coefficients when close touches were retained; the coefficient approached zero when touches with preceding intervals shorter than 100 ms were excluded. Excluding each touch that had another recorded onset within 50 ms before or after it left 12,773 touches, and 12,296 entered prediction models. In trials omitted from model fitting, adding phase to timing and task variables improved prediction of spike counts by 1.5 percentage points; the improvement was 0.8 points after movement variables were included. The gain varied across analysis settings and archive subject labels, the metadata labels used to group files. The interaction between amplitude and phase added a median 0.25 points (95% confidence interval, -0.02 to 1.50). Choices of counting window altered estimates of touch history, and phase added modest predictive information after movement adjustment. Touch-spacing and counting-window checks can improve attribution in studies using rapid sensory or neuroprosthetic stimulation.<b>NEW & NOTEWORTHY</b> Reanalysis of active touch recordings from excitatory layer 4 neurons shows that fixed windows indexed to a target touch can include spikes occurring after neighboring contacts and alter estimates of touch history. After touches with nearby onsets were excluded, whisking phase slightly improved prediction in trials omitted from model fitting. The improvement decreased after movement variables were added. Touch-spacing and window checks reveal whether rapid sequences affect history estimates.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"767-771"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of asymmetry across different submodalities of proprioceptive senses and motor skills of the hand in young adults.","authors":"Osman Barış Ünver, Erhan Nalçacı, Fikret Arı, İrem Kar","doi":"10.1152/jn.00476.2025","DOIUrl":"10.1152/jn.00476.2025","url":null,"abstract":"<p><p>Proprioceptive senses, particularly movement-position and force-effort senses enable individuals to perform essential motor functions. Despite their crucial role in the acquisition and execution of motor skills, proprioceptive assessment methods and the specific modalities they evaluate are not clearly defined in the literature. Furthermore, there is a lack of consensus regarding the laterality of proprioceptive senses in the upper extremities. The primary objective of this study is to examine the laterality and differences in movement-position and force-effort senses between the hands and to evaluate the relationship between motor skill laterality and various proprioceptive modalities in right-handers. Sixty healthy, right-handed participants aged 18-30 were included in the study. The finger tapping test (FTT) and Purdue Pegboard test (PPT) were used to assess motor skills. Active movement extent discrimination assessment (AMEDA) and targeted pinch force grading assessment (TPFGA) were used to assess proprioceptive senses. Proprioceptive tests did not show a significant difference between the hands. The dominant right hand performed better than the nondominant hand in both motor tasks (<i>P</i> < 0.001). No relationship was observed between motor and proprioceptive test results. Despite the dominant right hand's superior motor performance, no significant proprioceptive differences between hands were found. This suggests motor and proprioceptive asymmetries might differ between hands, and when the findings of this study are evaluated with previous studies, we claim that the current methods are insufficient in the thorough assessment of proprioceptive senses. Classifying proprioceptive measurement methods by active/passive movement and static/dynamic processes could greatly improve our understanding of sensorimotor issues and rehabilitation strategies.<b>NEW & NOTEWORTHY</b> No intermanual differences in proprioceptive performance for static tasks. No strong correlation between proprioceptive function and motor ability. Current assessment methods only capture limited aspects of the proprioceptive system. Implications on differences for static/dynamic components of proprioceptive senses.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"492-508"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional synaptic interactions and inhibitory circuitry of the pre-Bötzinger complex in the rhythmic slice.","authors":"Yaroslav I Molkov, Hidehiko Koizumi, Jeffrey C Smith","doi":"10.1152/jn.00235.2026","DOIUrl":"10.1152/jn.00235.2026","url":null,"abstract":"<p><p>The pre-Bötzinger complex (preBötC) within the medulla oblongata contains neuronal circuits critical for generating the mammalian respiratory rhythm, but the functional connectivity among its core excitatory and inhibitory populations remains debated. Defining this connectivity requires disentangling synaptic interactions of functionally identified excitatory and inhibitory preBötC neurons with various electrophysiological phenotypes. We applied a novel synaptic conductance inference method to whole cell recordings from genetically specified VgluT2-expressing (excitatory) and VGAT-expressing (inhibitory) preBötC neurons active in the rhythmic medullary slice in vitro, which contains core inhibitory-excitatory circuitry with an excitatory rhythmogenic kernel. We found that this circuitry consists of a self-exciting inspiratory VgluT2 population coupled to inspiratory and expiratory VGAT populations that interact reciprocally through inhibition. The functional inhibitory connectome is more complex than previously understood. However, compared with functional synaptic interactions inferred from recordings in the preBötC in situ, the neuronal synaptic conductance profiles in the rhythmic slice reveal a functionally reduced inhibitory connectome, characterized by prominent tonic expiratory inhibition and phasic inspiratory inhibition, without the characteristic multiphasic structure in situ. These results indicate that the functional excitatory and inhibitory circuit interactions within the preBötC isolated in vitro, although reduced relative to more intact states in situ, are intrinsically designed to generate coordinated inspiratory and expiratory population activity. Tonic expiratory phase inhibition together with inspiratory phasic inhibition serves to regulate excitability and phase transitions of the excitatory rhythmogenic kernel.<b>NEW & NOTEWORTHY</b> This study provides the first conductance-resolved mapping of synaptic interactions in genetically specified excitatory (VgluT2) and inhibitory (VGAT) pre-Bötzinger complex (preBötC) neurons within the rhythmic slice. Using a novel computational inference technique, we reveal that the core functional connectome relies on a self-exciting inspiratory core coupled to a reciprocal inhibitory loop. Crucially, we quantify how the network downshifts from a complex, multiphasic architecture in situ to a simplified, binary alternating pattern in vitro.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"837-853"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How visual context influences lateral stepping regulation while walking on winding paths.","authors":"Anna C Render, Tarkeshwar Singh, Joseph P Cusumano, Jonathan B Dingwell","doi":"10.1152/jn.00027.2026","DOIUrl":"10.1152/jn.00027.2026","url":null,"abstract":"<p><p>Goal-directed walking involves regulating foot placements to achieve specific tasks. This requires visuomotor integration. Perceptual, cognitive, and contextual salience guide attention and motor planning for navigation. Here, we quantified how perceptual salience informs lateral foot placement while walking. Participants walked along prescribed virtual paths (straight or winding), thus keeping contextual salience (the task itself) constant. We manipulated perceptual salience by systematically altering environment richness (rich vs. sparse) and path color contrast (high vs. low). We quantified head pitch angle to approximate gaze direction. We quantified lateral stepping regulation from a goal equivalent manifold framework. Our guiding hypothesis was that stepping arises from continuous decision-making action-perception processes: each step taken affects the decision of where to step next. This generated three testable predictions. First, that contextual salience alone (merely \"seeing\" the path) is sufficient for people to regulate stepping. However, while substantial between-path differences largely supported this, within-path differences in both head angle and stepping demonstrated that visual information (perceptual salience) also informs stepping. Second, we predicted perceptual salience of task-relevant visual information (here, of the path itself) is sufficient to guide stepping. However, while changing path color contrast did elicit more and greater changes than manipulating environmental richness, path visual saliency alone was not sufficient. Third, we predicted perceptual salience from peripheral vision also contributes to stepping. This prediction was supported, though less strongly than manipulating path visual saliency or contextual salience (straight vs. winding paths). Thus, both contextual and perceptual salience interact to influence step-to-step control of walking.<b>NEW & NOTEWORTHY</b> To walk in the real world, humans must navigate their environment (avoid obstacles, etc.) to reach their destination. People do this by taking steps, where each step affects the next. Here, we demonstrate how visual information contributes to such \"embodied decision-making\" during naturalistic walking. Context (the task), and both central and peripheral visual perception guide locomotor control of walking, down to the level of choosing where to take our next step.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"575-587"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}