Luis A Márquez, Gabriela Rocha-Botello, Emilio J Galván
{"title":"Group I metabotropic glutamate receptors are required for the induction of long-term depression at the medial perforant path-dentate gyrus synapse.","authors":"Luis A Márquez, Gabriela Rocha-Botello, Emilio J Galván","doi":"10.1152/jn.00190.2026","DOIUrl":"10.1152/jn.00190.2026","url":null,"abstract":"<p><p>Group I metabotropic glutamate receptors (mGluRs) modulate synaptic plasticity at most hippocampal synapses. However, the individual contribution of group I mGluRs to the induction of long-term depression (LTD) at synapses between the medial perforant path and dentate granule cells remains unclear. Using extracellular recordings in acute hippocampal slices and pharmacological manipulations of mGluR1 and mGluR5, we investigated their individual contributions to the induction of LTD. Our results demonstrate that although both receptors contribute to synaptic depression, activation of mGluR1 is critical for the induction phase, whereas activation of mGluR5 regulates the magnitude of synaptic depression. Analysis of short-term plasticity revealed that cooperative activation of both receptors maximizes the efficacy of short-term depression during low-frequency stimulation. Additionally, whole cell recordings showed that activation of group I mGluRs with (<i>R,S</i>)-3,5-dihydroxyphenylglycine (DHPG) modulates the voltage-dependent firing rate of mature granule cells. Together, these data reveal functional specialization of mGluR1 and mGluR5 in modulating LTD induction at the medial perforant path-dentate gyrus synapse.<b>NEW & NOTEWORTHY</b> We show a functional divergence between group I metabotropic glutamate receptor (mGluR) subtypes in the dentate gyrus. While mGluR1 is required for the induction of synaptic depression, mGluR5 serves as a key regulator of short-term plasticity, thereby gating the magnitude of subsequent long-term depression. These results refine our understanding of how group I mGluR subtypes cooperatively tune synaptic depression efficacy at the medial perforant path-dentate gyrus synapse.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1405-1415"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919714","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}
Pınar Toptaş, Ken Lew, Glingna Wang, Audrey E Kaye, Zachary M Leveroni, Jacob W Proctor-Bonbright, Uma Mani, Jaquelin Gutierrez, Bryan Garcia, Jai Y Yu
{"title":"Task-stage-specific modes of beta frequency coordination in the hippocampal-prefrontal network.","authors":"Pınar Toptaş, Ken Lew, Glingna Wang, Audrey E Kaye, Zachary M Leveroni, Jacob W Proctor-Bonbright, Uma Mani, Jaquelin Gutierrez, Bryan Garcia, Jai Y Yu","doi":"10.1152/jn.00232.2026","DOIUrl":"10.1152/jn.00232.2026","url":null,"abstract":"<p><p>Cognitive tasks typically consist of multiple stages with distinct computations. Yet, how oscillatory dynamics across distributed brain networks switch to support the computations required for each task stage remains poorly understood. The hippocampal-neocortical networks show prominent beta oscillations (15-30 Hz), which are hypothesized to facilitate long-range interactions required for a range of spatial, operant, and cue-based tasks. However, it is unknown how beta oscillations differentially modulate the hippocampal-neocortical networks to support specific cognitive processes for each task stage. To characterize beta oscillatory dynamics in hippocampal-neocortical networks, we recorded local field potential and single-unit activity in the CA1 region of the hippocampus and the prefrontal cortex (PFC) of the neocortex while rats performed an odor-guided two-alternative forced-choice task. We focused on two task stages requiring different cognitive processes: cue sampling and goal attainment. We found that these two stages showed unique patterns of beta-frequency coordination between the CA1 and PFC, including beta-subband-specific differences. Furthermore, we found that ensemble spiking activity patterns in the CA1 and PFC distinguished between the two task stages, with the CA1 expressing spatial and the PFC expressing nonspatial task correlates. Beta oscillations also showed task-stage-specific phase modulation of subsets of the CA1 and PFC populations. Our findings demonstrate that beta-frequency coordination in hippocampal-neocortical networks switches between functional modes, reconfiguring these networks to support the computational requirements for distinct stages within a cognitive task.<b>NEW & NOTEWORTHY</b> Our results demonstrate that beta-frequency dynamics in hippocampal-neocortical networks switch between distinct functional modes to support different cognitive processes within a task. These findings support the hypothesis that the hippocampus and neocortex may be members of different functional brain networks during different cognitive processes modulated by beta oscillations.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1510-1520"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002047","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}
Kristine McLellan, Yuhan Zhang, Mary Kate Tanselle, Sandesh Mohan, Jason Tait Sanchez
{"title":"Avian cochlear nucleus neurons exhibit tonotopic specializations across development.","authors":"Kristine McLellan, Yuhan Zhang, Mary Kate Tanselle, Sandesh Mohan, Jason Tait Sanchez","doi":"10.1152/jn.00159.2026","DOIUrl":"10.1152/jn.00159.2026","url":null,"abstract":"<p><p>Tonotopy is a hallmark feature of auditory structures that describes the spatial separation of sound frequencies along a gradient from high to low. Identifying biophysical differences along the frequency axis is essential for understanding how tonotopic maps develop in auditory structures and how these maps serve specific functions. In the mammalian cochlear nucleus and the analogous avian nucleus magnocellularis (NM), neurons are arranged along a tonotopic gradient resulting from ordered synaptic connections from the auditory nerve. Although mature NM neurons exhibit some intrinsic (i.e., ion channel) differences along the tonotopic axis, it is unclear whether these intrinsic properties of high- and low-frequency neurons diverge in phenotype across development or if they instead converge by embryonic maturation to resemble each other, suggesting offset developmental timelines. Using whole cell patch-clamp electrophysiology, we recorded from high- and low-frequency NM neurons in the embryonic chicken at early (E12-13), middle (E15-16), and late (E20-21) developmental stages. High- and low-frequency neurons differed in their action potential rise and repolarization rates during development, but these differences disappeared by late development, indicating a tonotopic developmental progression from high- to low-frequency neurons. However, neuronal input resistance, rheobase, and action potential latency were distinct across the tonotopic axis and remained so across development. High-frequency neurons had more low-voltage-activated potassium channels than low-frequency neurons at each developmental stage, thereby mediating differences in action potential properties. Overall, although some intrinsic properties converged in high- and low-frequency neurons by embryonic maturity, other disparities persisted, suggesting distinct phenotypes of high- and low-frequency neurons.<b>NEW & NOTEWORTHY</b> Auditory structures are organized along a tonotopic (i.e., frequency) axis from high- to low-frequencies. In the inner ear and auditory regions within the brainstem, high-frequency neurons develop earlier than low-frequency neurons. Our report challenges the notion that developmental differences along the tonotopic axis are solely attributable to a tonotopic developmental progression. In the avian cochlear nucleus, distinct intrinsic properties contribute to the varied developmental timeline, thereby promoting differential development along the tonotopic axis.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1416-1430"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912602","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":"Long-term ceftriaxone exposure modulates neuroplasticity in hippocampus.","authors":"Mohadeseh Giahi, Negin Saeedi, Zohreh Tavassoli, Fatemeh Rostami, Mahyar Janahmadi, Narges Hosseinmardi","doi":"10.1152/jn.00547.2025","DOIUrl":"10.1152/jn.00547.2025","url":null,"abstract":"<p><p>The glial glutamate transporters play a crucial role in clearing glutamate from the synaptic space, thereby regulating its concentration and maintaining synaptic homeostasis. As the main glutamate transporter in astrocytes, GLT-1 ensures efficient neurotransmitter clearance, contributing to the excitatory-inhibitory balance in neural circuits. Given its essential role in synaptic function, modulation of GLT-1 has been explored as a potential approach to altering synaptic transmission and plasticity. The objective of this study was to examine hippocampal synaptic plasticity in juvenile rats following the administration of Ceftriaxone (CTX), a compound widely reported to influence GLT-1 function and glutamate homeostasis. Our study primarily focused on functional electrophysiological outcomes rather than direct molecular measurements. A 0.5-μL intracerebroventricular (ICV) microinjection of 0.5 mM Ceftriaxone was administered to male Wistar rats. Field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region following Schaffer collateral stimulation. The study found that 29 days of CTX treatment significantly weakened long-term potentiation (LTP) in CA3-CA1 synapses. A significant decrease in the paired-pulse index was observed following ceftriaxone injection at interpulse intervals (IPIs) of 20 and 80 ms. Compared with the control group, the Ceftriaxone-treated group showed a significantly higher maximum current intensity required to elicit the maximal synaptic response. This study suggests that, beyond its antimicrobial properties, Ceftriaxone can significantly influence electrophysiological properties in the hippocampus. Such findings highlight the significant impact of ceftriaxone on synaptic function and suggest its potential to modulate neural network activity.<b>NEW & NOTEWORTHY</b> Long-term intracerebroventricular ceftriaxone, a GLT-1 activator, was tested in vivo in juvenile rats without a disease model. Our results reveal three reliable effects in CA3-CA1 synapses: attenuated LTP, reduced paired-pulse indices, and a shift in the input-output curves (higher current needed for maximal response). Together, these data reveal that sustained astrocytic glutamate clearance dampens excitatory gain under strong input, extending prior slice or short-term studies to a chronic in vivo context.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1521-1527"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061652","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}
Yannick Finck, Demetris S Soteropoulos, Alessandro Del Vecchio
{"title":"State- and identity-dependent motor neuron excitability shapes cutaneous long-latency reflexes.","authors":"Yannick Finck, Demetris S Soteropoulos, Alessandro Del Vecchio","doi":"10.1152/jn.00225.2026","DOIUrl":"10.1152/jn.00225.2026","url":null,"abstract":"<p><p>Neuromuscular reflexes elicited by sensory nerve stimulation provide valuable insights into neural motor control pathways. Analysis at the level of individual motor units (MUs) is feasible via electromyographic decomposition, but the factors shaping MU-specific reflex responses remain poorly understood. We investigated long-latency responses to cutaneous electrical stimulation in a large population of tibialis anterior MUs from nine healthy subjects during isometric ankle dorsiflexion at 10-30% of maximum voluntary contraction. Individual MU reflex responses differed markedly. Using 1,000 stimulation pulses per trial, substantially more than the 150-300 typically reported in previous studies, provided more reliable estimates of cutaneous reflex characteristics. Across the motor pool, reflex magnitude increased with force level (<i>P</i> < 0.001) while excitation probability correlated significantly with MU recruitment threshold in 78% of subjects (<i>P</i> = 0.012). Furthermore, excitation probability increased systematically with contraction intensity (<i>P</i> < 0.001) for individually tracked MUs. Postexcitatory depression (PED) magnitude correlated significantly with excitation probability (<i>r</i> = 0.50, <i>P</i> < 0.001) of individual MUs. A targeted reflex-removal analysis, validated by MU simulations incorporating realistic excitation probabilities into ordinary firing patterns, reduced the PED by 84.2% in simulated data but only by 34.7% in recorded units. These findings suggest that the PED is a complex, hybrid phenomenon, resulting from synchronization-induced discharge resetting and additional independent inhibitory components. These findings demonstrate that MU-level reflex excitability to somatosensory input is influenced by state- and identity-dependent motor neuron characteristics, underscoring the importance of using sufficient stimulation pulses for reliable reflex measures and MU population analysis.<b>NEW & NOTEWORTHY</b> We show that cutaneous long-latency reflex excitability at the single motor unit level scales with force via two mechanisms: high-threshold units show comparable reflex gain despite biophysical disadvantage, while active units increase excitation probability as drive rises. We further show postexcitatory depression is a hybrid phenomenon combining synchronization-induced spike resetting and, presumably, centrally mediated inhibition. Estimating single-unit reflex characteristics with 1,000 stimuli also proved significantly more reliable than in previous work using at most 300 repetitions.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1528-1543"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001919","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}
Anjana Rajendran, Ronan Denyer, Cristina Rubino, Jason L Neva, Lara A Boyd
{"title":"Exploring interneuron conduction time in the motor cortex and the link to motor function in individuals with chronic stroke.","authors":"Anjana Rajendran, Ronan Denyer, Cristina Rubino, Jason L Neva, Lara A Boyd","doi":"10.1152/jn.00103.2026","DOIUrl":"10.1152/jn.00103.2026","url":null,"abstract":"<p><p>Interneurons in the motor cortex (M1) contribute to key motor functions, which are often altered after stroke. Changing the direction of transcranial magnetic stimulation (TMS) alters the onset time of motor evoked potentials (MEPs). Yet, how stroke changes motor evoked potential (MEP) onset latency in association with directional TMS is not understood. The goals of the current study were to <i>1</i>) investigate directional MEP onset in the contralesional and ipsilesional hemispheres and <i>2</i>) characterize the relationship between MEP onset latency and motor function poststroke. Twenty individuals with chronic stroke received single-pulse, monophasic TMS over M1 in the lateral-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) directions. Latency of activation of the corticospinal tract was indexed by subtracting MEP onset times from the paretic and nonparetic extensor carpi radialis (ECR) muscle in the LM direction from the AP and PA directions in both hemispheres. Upper limb motor function was quantified using the wolf-motor function test (WMFT). There was a significant difference between AP-LM and PA-LM MEP onset latencies within and between hemispheres. AP-LM MEP onset latency was longer in the contralesional than the ipsilesional hemisphere. Hemispheric differences in AP-LM MEP onset latency explained a significant proportion of variance in WMFT performance between limbs. AP-LM MEP onset latency is altered poststroke, and larger hemispheric imbalances in AP-LM MEP onset times related to worse motor function. These data highlight a new relationship between connectivity of interneuron pools in the human motor cortex and motor function after stroke.<b>NEW & NOTEWORTHY</b> AP-LM was greater than PA-LM MEP onset latency after stroke in both the ipsilesional and contralesional hemispheres, following patterns previously noted in healthy brains. However, AP-LM MEP onset latency was shorter in the ipsilesional hemisphere than the contralesional hemisphere. AP-LM, but not PA-LM, MEP onset differences between hemispheres were related to upper limb motor function after stroke. These data suggest that interneuron onset timing could be a motor function recovery biomarker after stroke.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1349-1358"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880159","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}
Alexandre Nicholas Kalogerakis, Paul C Yielder, Hailey Tabbert, Ushani Ambalavanar, Bernadette Murphy
{"title":"Neck muscle vibration before visuomotor task acquisition impacts early somatosensory evoked potential amplitudes in individuals with subclinical neck pain.","authors":"Alexandre Nicholas Kalogerakis, Paul C Yielder, Hailey Tabbert, Ushani Ambalavanar, Bernadette Murphy","doi":"10.1152/jn.00081.2026","DOIUrl":"10.1152/jn.00081.2026","url":null,"abstract":"<p><p>Subclinical neck pain (SCNP) is associated with altered sensorimotor integration, proprioception, and somatosensory evoked potentials (SEPs) in response to visuomotor tracing task acquisition. Neck muscle vibration (NMV) in healthy adults impairs upper limb proprioception and motor skill acquisition. In contrast, NMV improves neck and elbow joint position sense in participants with neck pain, but neurophysiological responses have not been measured. This study aimed to investigate the effects of NMV on SEP changes postacquisition of a novel motor tracing task (MTT) in those with SCNP. Twenty-three right-handed participants with SCNP were divided into vibration (age: 22.4 ± 3.44, <i>n</i> = 12; 6 females) (V) and no-vibration (NV) (age: 22.5 ± 4.69, <i>n</i> = 11; 7 females) groups. Short-latency SEPs were elicited via right median nerve stimulation at 2.47 Hz and 4.98 Hz, before and after MTT acquisition. Following preacquisition MTT, V received 10 min of 60-Hz vibration over the right sternocleidomastoid and left cervical extensor muscles, while NV rested for 10 min, followed by acquisition and postacquisition phases with retention assessed 24 h later. Significant time-by-group interactions were observed for: N18 SEP: decreased 55.7% for V and 20.4% for NV (<i>P</i> = 0.028); N24 SEP: 22.9% decrease for V and 13.6% increase in NV (<i>P</i> = 0.010). Error decreased postacquisition: 20% in V and 23.6% in NV; during retention, errors further decreased 7.7% in V and 4.4% in NV with no group differences (<i>P</i> < 0.001). V had differential changes in SEP peaks at the level of the olivary-cerebellar pathway (N18) and cerebellar-somatosensory pathway (N24) in those with SCNP.<b>NEW & NOTEWORTHY</b> This is the first study to our knowledge assessing the impact of vibration on neural processing and motor learning in those with subclinical neck pain (SCNP). Prior literature has examined vibration's effect on joint position sense and pain. However, we demonstrated alterations in cerebellar and somatosensory processing via early SEP peak changes in those with SCNP receiving vibration. This may provide insight for future research examining long-term effects of alterations on cerebellar and cortical processing.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1580-1589"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025155","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":"Correction for Bedoy et al., volume 133, 2025, p. 299-309.","authors":"","doi":"10.1152/jn.00354.2024_COR","DOIUrl":"https://doi.org/10.1152/jn.00354.2024_COR","url":null,"abstract":"","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":"136 4","pages":"1606"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182540","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":"Age-related decline in vestibulo-ocular reflex gain is associated with an increased sway response to electrical vestibular stimulation.","authors":"Callum J Osler, Raymond F Reynolds","doi":"10.1152/jn.00110.2026","DOIUrl":"10.1152/jn.00110.2026","url":null,"abstract":"<p><p>Despite considerable loss of peripheral vestibular input with age, there is relatively little change in function. This has led to speculation that increasing central neural gain mitigates such losses. Here, we test this hypothesis by comparing the gain of the vestibulo-ocular reflex (VOR) with the response to electrical vestibular stimulation (EVS) across the lifespan. The VOR assesses the full vestibulo-motor pathway, whereas EVS bypasses the peripheral vestibular mechanics. Hence, any dissociation between the two may reveal a difference in central versus peripheral function. A rotating chair was used to assess VOR gain in 62 participants aged 20-87 yr. EVS-evoked postural sway responses were then tested in the same participants on the same day. We found a significant age-related reduction in VOR gain (<i>r</i> = -0.48, <i>P</i> < 0.001), an increase in EVS gain (<i>r</i> = 0.36, <i>P</i> = 0.004), and an inverse correlation between the two (<i>r</i> = -0.35, <i>P</i> = 0.006). The EVS response is consistent with an increase in central neural gain. We also observed an increase in VOR phase lead with age. This may impair VOR accuracy, thus imposing limits on the extent of compensation, explaining why VOR gain declined with age. These results demonstrate partial neural compensation for age-related peripheral loss. However, the inverse correlation between VOR and EVS gain persisted even when age was factored out (<i>r</i> = -0.28, <i>P</i> = 0.031). This suggests a general property of the central nervous system whereby neural gain is tuned to match interpersonal differences in peripheral vestibular input.<b>NEW & NOTEWORTHY</b> Up to 40% of vestibular hair cells are lost by age 70, but eye movements are only mildly affected, suggesting peripheral loss is mitigated by increasing neural gain. We investigated this hypothesis by applying electrical vestibular stimulation (EVS) to estimate central gain in volunteers aged 20-87 yr. EVS-evoked balance responses systematically increased with age, whereas vestibular-ocular reflex gain reduced. This is consistent with an increase in central neural gain to compensate for age-related peripheral loss.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1359-1368"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919696","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}
Amit Kadosh, Orit Wonderman Bar Sela, Shay Ofir Geva, Afnan Muhana, Silvi Frenkel-Toledo, Nachum Soroker, Firas Mawase
{"title":"Motor cortex contribution to dynamic force regulation in the index finger revealed by TMS interference.","authors":"Amit Kadosh, Orit Wonderman Bar Sela, Shay Ofir Geva, Afnan Muhana, Silvi Frenkel-Toledo, Nachum Soroker, Firas Mawase","doi":"10.1152/jn.00057.2026","DOIUrl":"10.1152/jn.00057.2026","url":null,"abstract":"<p><p>Lifting a paper cup without crushing it requires precise regulation of finger force. In humans, such control is thought to rely primarily on the contralateral corticospinal tract (CST), but the cortical mechanisms underlying graded force modulation remain unclear. To address this, we used online repetitive transcranial magnetic stimulation (rTMS) as a transient interference during an isometric index finger force-tracking task. Eleven healthy adults increased and decreased index finger isometric force at low (0-20% maximal voluntary contraction, MVC) and high (0-60% MVC) levels, while 2-s trains of 10-Hz rTMS were delivered over contralateral or ipsilateral primary motor cortex (M1; cM1, iM1) or a midline control site (Pz). Accuracy, consistency, and force smoothness were quantified using RMSE, SDAE, and normalized YankRMS within the 2-s stimulation windows, and outcomes were normalized to Pz. Factorial mixed-effects analysis showed a significant main effect of stimulation-site (Condition) across all three measures (all <i>P</i> < 0.0022). Holm-adjusted comparisons showed greater disruption during cM1 than iM1 stimulation and no-TMS, whereas iM1 did not differ from no-TMS. For YankRMS, the condition × intensity interaction was significant (<i>P</i> = 0.0031), with a larger cM1-iM1 difference at the higher force level (60% MVC) than at the lower force level (20% MVC; interaction contrast, <i>P</i> = 0.0033). No other task-dependent interactions were significant. These findings provide time-locked causal evidence that ongoing cM1 activity is essential for dynamic index finger force regulation, with the contralateral-ipsilateral asymmetry becoming more pronounced at higher force demands.<b>NEW & NOTEWORTHY</b> Fingertip force regulation underlies everyday grasping, lifting, and object release. Although the corticospinal tract supports skilled hand control, the causal role of motor cortex in graded force modulation is unclear. Using online rTMS during isometric tracking, we show that interference over contralateral M1 disrupts accuracy, consistency, and force smoothness more than ipsilateral M1 interference. The contralateral-ipsilateral difference in force smoothness was larger at higher forces, identifying force demand as a determinant of motor-cortical involvement in fine force control.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1654-1665"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025103","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}