Journal of Neurophysiology

Plantard, Arthur; Séry, Romain; Pichot, Vincent; Chouchou, Florian

doi: 10.1152/jn.00118.2025pmid: 40691044

The heartbeat-evoked potential (HEP) is a growingly used electrophysiological method to study cardiac interoception; however, cardiovascular influences on these responses are not fully understood. In the present study, we studied the effect of changes in blood pressure through positional modifications and slow-paced breathing on HEP. 18 volunteers (22 ± 1.79 years old) underwent 5-min tasks in upright and supine positions, with spontaneous and slow-paced breathing at 6 cycles/min. We continuously recorded blood pressure, electrocardiography and high-density (128 electrodes) electroencephalography (EEG). We observed an increase in early (around 200 ms) and late (around 400 ms) HEP components in the supine position (p<0.001) and more pronounced with slow-paced breathing (p<0.001). HEP exhibited a frontocentral topography and source modeling indicated mainly insular and cingulate cortex of the early component, which extended to frontal regions during the late component (p<0.05). Diastolic (DBP) and pulse (PBP) blood pressure increased in an upright position (p<0.05), whereas baroreflex sensitivity (BRS) increased in the supine position (p<0.001). Changes in early and late HEP were mainly correlated to changes in PBP (r = 0.55; r = 0.49, respectively p<0.001), DBP (r = −0.35; r = −0.35, p<0.010) and BRS (r = 0.61; r = 0.47, p<0.001). The present study demonstrated modulations of HEP according to cardiovascular activities, suggesting a heightened integration of baroreflex afferents by positional modulations and to a lesser extent in respiratory modulations. These changes should be considered in assessments of interoception in clinical populations.

Hill, Ethan C.; Proppe, Christopher E.; Lubiak, Sean M.; Howard, Mason A.; Prajapati, Anuj J.; Shah, Niriham M.; Patel, Nihar N.; Rivera, Paola M.; Zak, Roksana B.; Schmidt, Jeffrey T.; Trevino, Michael A.

doi: 10.1152/jn.00197.2025pmid: 40758611

Introduction: Muscle fatigue is a prevalent and challenging symptom in people with multiple sclerosis (PwMS), typically involving pronounced central (e.g., reduced corticospinal excitability) and relatively lower peripheral contributions (e.g., metabolic stress) compared to healthy controls. Blood flow restriction (BFR) applied during resistance exercise is an innovative approach to facilitate exercise benefits among PwMS. Therefore, the purpose of this investigation was to examine how distinct resistance exercise approaches including high-load (HL), low-load (LL), and LL with blood flow restriction (LLBFR) affect central and peripheral fatigue when applied in a clinically-relevant, real-world context.Methods: Twelve females (42±12 yrs) and three males (41±10 yrs) with MS performed unilateral leg extensions with a HL (3×12 at 70% of one repetition maximum [1RM]), LL (1×30, 3×15 at 30% 1RM), and LLBFR (LL with 60% limb occlusion pressure). Prior to and immediately after each exercise bout, maximal voluntary isometric contraction (MVIC) torque and indices of central (surface electromyographic [sEMG] amplitude, superimposed twitch torque [STT], VWAVE/MWAVE) and peripheral (potentiated twitch torque [PTT]) fatigue were assessed.Results: There were similar acute decreases in MVIC torque (− 21.0% relative to baseline; p<0.001, g=1.486), but exercise-specific decreases in PTT between LLBFR (−37.1%; p<0.001, g=1.135) and HL (−14.2%; p=0.093, g=0.440). STT increased (+24.5%, p=0.018, g=0.650), while there were decreases in sEMG amplitude (−9.7%; p=0.004, g=0.852) and VWAVE/MWAVE (−7.9%; p<0.001, g=1.037) that were not different among conditions.Conclusions: LLBFR may represent a more effective resistance exercise strategy for PwMS due to its ability to induce greater peripheral fatigue, a proxy for metabolic stress.

Cyr, Jean-Philippe; Crepin, Roxane; Mercier, Pierre; Blouin, Jean-Sébastien; Simoneau, Martin

doi: 10.1152/jn.00238.2025pmid: 40803774

Scoliosis is a spinal deformity characterized by lateral deviation and rotation of the vertebrae, affecting between 0.47% and 5.2% of adolescents. A proposed explanation for adolescent idiopathic scoliosis (AIS) is asymmetric vestibular function affecting the descending control of torso muscles. To verify this hypothesis, we applied stochastic vestibular stimulation (SVS) at frequencies of up to 25 Hz, both monaurally and binaurally, to standing participants with AIS (n = 15) and to those without AIS (n = 15). We characterized potential left-right vestibulomotor asymmetry in the correlations, gain, and direction of the evoked balance responses. Contrary to our hypothesis, no asymmetry in the balance responses evoked by monaural stimuli was observed in either group. AIS participants, however, exhibited larger correlations and gains (both in the frequency and time domains, except for time domain estimates to monaural right stimuli) between vestibular stimuli and ground reaction forces compared to control participants. This larger coupling suggests a greater association between the vestibular error and force signals in AIS participants for monaural left and binaural SVS conditions. The orientation of the vestibular-evoked balance responses, however, did not differ between groups. We conclude that adolescents with idiopathic scoliosis exhibit larger vestibular gains than controls. This suggests an enhanced relationship between the electrical vestibular error signal and the evoked balance responses. Still, these changes do not affect the symmetry or orientation of vestibular-evoked postural responses at the tested frequencies.

Yuasa, Akiko; Uehara, Shintaro; Liu, Boqun; Otaka, Yohei

doi: 10.1152/jn.00064.2025pmid: 40758604

The motor system continuously receives sensory inputs and uses this information to perform purposeful movements in a process known as sensorimotor integration. As a biomarker of sensorimotor integration efficacy, short-term afferent inhibition (SAI), the phenomenon whereby afferent sensory inputs inhibit cortical motor outputs in a given muscle, has been widely studied in humans. However, it remains unclear how the (sensory) nerve-muscle relationship, that is, anatomical proximity and homotopy (nerve-supply to muscles), affects SAI magnitude. To address this question, we assessed SAI magnitudes in cortical motor excitability by examining the size of the motor representations of two intrinsic hand muscles when afferent inputs were provided to the nerves either innervating or non-innervating to the muscles. In sixteen healthy adults, we measured the effect of conditioning electrical stimuli to the median nerve (MN) or ulnar nerve (UN) at the wrist on motor evoked potentials induced by transcranial magnetic stimulation in the first dorsal interosseous (FDI, innervated by UN) and abductor pollicis brevis (APB, innervated by MN) muscles, both of which are anatomically located closer to MN than to UN. Conditioning MN stimulation resulted in a significant SAI in both muscles, with no significant difference in SAI between the muscles. No clear SAI was found in either muscle with the UN stimulation. These results suggest that SAI magnitude may depend on anatomical proximity rather than on homotopy. Given the inhibition of motor representation size of both muscles, the specific nature of such SAI may contribute to the synergistic coordination between muscles.

Goudsward, Hannah J.; Ruiz-Velasco, Victor; Stella, Salvatore L.; Holmes, Gregory M.

doi: 10.1152/jn.00230.2025pmid: 40763064

Upper gastrointestinal dysfunction is one of the most common comorbidities of spinal cord injury (SCI) and significantly impairs overall health and quality of life. Despite the need for targeted treatment options, the causal mechanisms underlying upper gastrointestinal dysfunction after injury remains unknown. Previous studies have demonstrated gastric vagal afferents are less sensitive to stimuli after SCI, which may be due to changes in voltage-gated Ca2+ (CaV) channels in gastric-projecting nodose ganglia (NG) neurons, as they contribute to action potential initiation along vagal afferents and neurotransmitter release at central synapses. Therefore, the purpose of this study was to investigate whether altered function of CaV channels in gastric NG neurons develops after upper thoracic SCI using whole-cell patch-clamp electrophysiology. Although no change in the biophysical properties of CaV channels were observed 3-days post-injury, there was a significant (p=0.0006) reduction in the Ca2+ current density in gastric NG neurons isolated from 3-week SCI animals as compared to controls (16.41±2.41 pA/pF vs 39.92±5.63 pA/pF). When evaluating the CaV channel expression profile, we found the CaV2.2 blocker ω-conotoxin produced the largest Ca2+ current inhibition in the 3-day SCI (60.0±6.6%, n=13), 3-week SCI (59.4±6.7%, n=15), and control groups (3-day: 67.4 ±8.1%, n=11; 3-week: 58.3 ± 5.0%). However, the effect of ω-agatoxin was significantly (p= 0.0225) higher in the 3-week SCI group compared to the 3-day SCI group. These findings suggest CaV channel currents are reduced following 3-week SCI in gastric NG neurons, offering necessary insights into the cellular mechanisms underlying vagal afferent hyposensitivity post-injury.

Butler, Carley L. P.; Lee, Minkyu; Perez, Monica A.

doi: 10.1152/jn.00168.2025pmid: 40691051

Animal and human studies indicate that monosynaptic corticospinal connections are more prevalent in biceps than triceps brachii motoneurons. Based on this evidence, we hypothesized that Hebbian stimulation, which targets corticospinal-motoneuronal connections, would enhance corticospinal excitability more in the biceps than the triceps brachii. To test this hypothesis, we assessed motor evoked potential (MEP) size using transcranial magnetic stimulation (TMS) at resting motor threshold (MEP-RMT) and maximum stimulator output (MEP-100%) immediately and up to 30 minutes post-stimulation. During Hebbian stimulation, 180 paired pulses were delivered, with corticospinal volleys evoked by TMS arriving at corticospinal-motoneuronal synapses 1–2 ms before antidromic potentials from brachial plexus electrical stimulation. Central and peripheral conduction times were similar between muscles. We found that both MEP-RMT and MEP-100% increase in the biceps and triceps immediately and up to 30 min post-stimulation. The increase in MEP-RMT was greater in the biceps compared to the triceps, while MEP-100% changes did not differ between muscles. Since the maximum MEP size was larger in the biceps than in the triceps, we conducted a control experiment testing responses at an intermediate size between MEP-RMT and MEP-100% (MEP-Control), ensuring similar baseline sizes between muscles. Notably, Hebbian stimulation continued to produce a greater increase in MEP-Control in the biceps than in the triceps. These findings suggest that Hebbian plasticity enhances corticospinal excitability more in elbow flexor than extensor muscles, emphasizing the need to consider muscle-specific innervation patterns when future studies assess the therapeutic effect of this technique in individuals with motor impairment.

Ito, Mio; Ito, Takanori; Funakoshi, Hayase; Takahata, Kei; Suresh, Nina L.; Kokubun, Takanori

doi: 10.1152/jn.00179.2025pmid: 40796243

Voluntary contraction anomalies of post-stroke survivors progress from flaccid paralysis to recovery of upper extremity motor function in the subacute phase. However, muscle weakness often persists, and it is unclear what changes or aberrations persist in neuromuscular function, particularly in motor unit behavior. Our objective was to characterize motor unit discharge behavior in hemiplegic stroke patients in the subacute phase. We tested seven subacute stroke patients at two-time points (Timepoint 1 and 2) a minimum of two weeks apart during the subacute phase. We used wireless surface electromyography to detect motor unit activities on both sides of our tested participants. Participants carried out two types of target force tracking tasks with isometric elbow flexion. We performed Two-way ANOVA between the time point and test side. The recruitment threshold force (RTF) of the Ramp task exhibited a significant interaction between the Timepoint and Test side (p < 0.00). The post hoc test showed the RTF of the affected side was not significantly lower than the contralateral side (p = 0.99) at Timepoint 1. On the other hand, the affected side at Timepoint 2 was significantly lower than the contralateral side (p < 0.00). The low recruitment threshold on the affected side may be more exacerbated than the contralateral side chronologically during the subacute phase of stroke. Our results suggest that the assessment of motor units in the subacute phase of stroke can contribute to the early detection of abnormal neuromuscular activity and, thereby, the establishment of effective rehabilitation.

Orguc, Sirma; Kwon, Ohyoon; Naranjo Gonzalez, Marusa; Brown, Emery N.

doi: 10.1152/jn.00091.2025pmid: 40673931

Objectives: Propanidid is an intravenous short-acting sedative-hypnotic anesthetic in the eugenol family that acts as a positive allosteric modulator of the gamma-aminobutyric acid type A (G A B A A) receptor. However, its neural circuit mechanisms have not been characterized. We compared the EEG signatures of patients anesthetized with propanidid to those anesthetized with propofol.Methods: We characterized the EEG recordings of 13 propanidid- and 13 propofol-mediated general anesthesia cases using spectral and coherence analyses.Results: During propanidid-mediated unconsciousness, we observed a significant increase in the 0-18.5 Hz power and a decrease in the 30.5-40 Hz power compared to the baseline. Compared to the propofol cohort, the suppression in the 23-40 Hz band power was significantly less in the propanidid cohort during unconsciousness. The coherence in the 0-40 Hz range was not significantly different between the two cohorts. The propanidid cohort showed a shorter average offset time (4.8 minutes) than the propofol cohort (5.9 minutes) which was not significant.Conclusions: This preliminary investigation showed that the EEG signatures of propanidid-mediated unconsciousness are similar to those of propofol suggesting a similar GABAergic mechanism of network action.Significance: Our work provides a basis to characterize the neural mechanisms of propanidid-mediated sedation and unconsciousness.