Brain Research

Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) was shown to impair short-term consolidation of a balance task, emphasizing the importance of M1 in balance skill consolidation. However, the disruptive mechanisms of rTMS on neural consolidation processes and their persistence across multiple balance acquisition sessions remain unclear. GABAergic processes are crucial for motor consolidation and, at the same time, are up-regulated when learning balance skills. Therefore, this study investigated the impact of rTMS on GABA-mediated short-interval intracortical inhibition (SICI) and consolidation of balance performance. Participants (n=31) underwent six balance acquisition sessions on a rocker board, each followed by rTMS (n=15) or sham-rTMS (n=16). In the PRE-measurement, SICI was assessed at baseline and after balance acquisition with subsequent rTMS/sham-rTMS. In the POST-measurement, this procedure was repeated to assess the influence of motor memory reactivation on SICI. In addition, SICI-PRE and SICI-POST were compared to assess long-term processes. Both groups achieved similar improvements within the balance acquisition sessions. However, they did not consolidate equally well indicated by significant declines in performance for the rTMS group (p = 0.006) in the subsequent sessions. Both short-(p = 0.014) and long-term (p = 0.038) adaptations in SICI were affected by rTMS: while the sham-rTMS group up-regulated SICI, rTMS led to reductions in inhibition. The interfering effect of rTMS on both balance consolidation and up-regulation of SICI suggests that increased intracortical inhibition is an important factor to protect and consolidate the newly acquired motor memory.

The pleasurable urge to move in response to music is called groove. Prior research has suggested a potential link between groove and dopamine function. However, no studies to date have directly investigated the relationship between the two. Here, we aimed to assess individual dopamine function in the substantia nigra of healthy individuals using neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a non-invasive method associated with dopamine function, and to investigate the relationship between the individual dopamine proxy index and sensitivity to the groove experience. In this study, 15 younger (< 48 years) and 16 older ([greater double equals]48 years) healthy individuals participated. Participants listened to ten musical excerpts and rated the groove experience based on "pleasure" and "wanting to move." To assess whether the groove experience is related to NM levels, type of musical excerpts, and sex, we analyzed with linear mixed-effects regression models. The results showed that higher NM levels (p = 0.032) and male sex (p = 0.034) were associated with higher pleasure ratings in the younger group. For the "urge to move" ratings, type of musical excerpts was associated with ratings in both groups (ps < 0.001), where high-groove music (Janata et al., 2012) receiving higher ratings. Taken together, these results suggest that the "pleasure" aspect of the groove experience in younger individuals was related to dopamine levels in the substantia nigra, but may not be associated with the "urge to move." Thus, pleasure and the urge to move are likely to involve distinct dopaminergic pathways and mechanisms, warranting further investigation.

Acute aerobic exercise (AAE) can modulate primary motor cortex (M1) excitability. To date, studies evaluating the effects of AAE on M1 excitability have focused almost exclusively on concentric cycling. Interestingly, eccentric cycling increases frontal-parietal brain activation more than concentric cycling. Critically, we recently found eccentric AAE enhances motor learning more than concentric AAE. Yet, the M1 excitability mechanisms underlying these effects remain unknown. Thus, the objective of this study was to evaluate the effect of eccentric cycling AAE on M1 excitability using transcranial magnetic stimulation (TMS). Thirty adults performed three 20 min-conditions: i) eccentric cycling AAE, ii) concentric cycling AAE, and iii) rest. Cycling AAE was carried out at a workload corresponding to 70% of peak heart rate (%HRpeak) measured during concentric incremental cycling exercise. TMS assessments were conducted before (Pre), immediately (Post0) and 20 minutes after (Post20) AAE/rest to evaluate changes in corticospinal excitability (CSE) and short interval-intracortical inhibition (SICI). We found CSE increased and SICI decreased at Post20 following eccentric and concentric cycling AAE compared to rest. Also, %HRpeak, muscle pain and perceived effort were lower during eccentric cycling AAE compared to concentric cycling AAE. Our results showed that eccentric cycling impacted M1 excitability change to a comparable degree as concentric cycling, while requiring less cardiovascular response, eliciting less muscle pain and lower perceived effort. Taken together, our results suggest that eccentric cycling AAE may be a valuable intervention to modulate M1 excitability for populations with limited cardiovascular capacity and have potential implications in clinical and sports-related contexts. New and NoteworthyThis study demonstrates that both eccentric and concentric cycling exercise enhance corticospinal excitability and reduce short-interval intracortical inhibition. Additionally, eccentric cycling elicited significantly lower cardiovascular and perceptual responses compared to concentric cycling. These findings suggest that eccentric cycling may be a useful intervention for individuals with limited exercise capacity, such as clinical or aging populations.

Acute aerobic exercise (AEX) can enhance motor learning and promote neuroplasticity. However, the effect of AEX intensity on primary motor cortex (M1) excitability has not been systematically examined. Hence, the dose-response relationship between AEX intensity and M1 excitability modulation remains unclear. This study investigated the impact of AEX intensity on distinct M1 circuits using transcranial magnetic stimulation (TMS). Thirty right-handed adults underwent four experimental sessions: rest (control), light (LIIT), moderate (MIIT), and high-intensity interval training (HIIT) AEX. AEX intensity was prescribed with the heart rate reserve (HRR) method, and the interval cycling sessions consisted of alternating between 3 min at the target intensity (LIIT: 35% HRR; MIIT: 55% HRR; HIIT: 80% HRR) and 2 min of active recovery (25% HRR) for 20 min total. We performed TMS measures before (Pre), immediately post (Post0), and 20 min post (Post20) AEX/rest to assess modulation of corticospinal excitability and GABAergic inhibition as measured by short interval-intracortical inhibition (SICI). This study found that: (1) HIIT and MIIT increased corticospinal excitability, with HIIT eliciting a sustained increase; and (2) all AEX intensities (LIIT, MIIT and HIIT) decreased SICI, with the greatest sustained reduction following MIIT. Also, there was a greater reduction in GABAergic inhibition when measured with anterior-posterior than posterior-anterior TMS current following MIIT. Collectively, our results demonstrate the impact of HIIT and MIIT to enhance corticospinal excitability and reduce GABAergic inhibition in M1. This study provides evidence for a dose-response effect of AEX intensity on the modulation of distinct motor cortical circuits. KEY POINTS SUMMARYO_LIAcute aerobic exercise (AEX) is known to modulate primary motor cortex (M1) excitability, but the effect of AEX intensity is unclear. C_LIO_LIThis study examined the impact of light-, moderate-, and high-intensity interval training (LIIT, MIIT, HIIT) AEX and rest (non-AEX, control) on distinct M1 cortical circuits using transcranial magnetic stimulation (TMS). C_LIO_LIHIIT induced a sustained increase in M1 output excitability, MIIT induced a transient increase, and LIIT showed no effect. C_LIO_LIAll exercise intensities (LIIT, MIIT and HIIT) decreased GABAergic inhibition, as measured by short-interval intracortical inhibition (SICI), with MIIT showing a sustained decrease. C_LIO_LISICI measured with an anterior-to-posterior TMS current demonstrated greater GABAergic disinhibition compared to posterior-to-anterior TMS current following MIIT. C_LIO_LIThis study demonstrates a nuanced dose-response impact of AEX intensity on distinct M1 cortical circuits. C_LI

Although the autonomic sympathetic system is activated in parallel with locomotion, the underlying neural mechanisms mediating this coordination are not completely understood. Descending exercise or central command signals from hypothalamic and brainstem regions are thought to activate thoracic spinal sympathetic neurons in parallel with descending locomotor commands. In turn, subsets of thoracic sympathetic preganglionic neurons (SPNs) then increase activation of a constellation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. It is known that neurons within the spinal cord (propriospinal networks) can generate well-coordinated and sustained locomotor activity but whether these propriospinal networks contribute to coordination between locomotor and autonomic systems is unknown. To investigate this, we applied neurochemicals to elicit whole-cord or lumbar-evoked locomotor activity in an in vitro spinal cord preparation, simultaneously recording lumbar ventral root (VR) activity and changes in calcium fluorescence of pre-labelled SPNs in thoracic segments. Using whole-bath drug application to elicit hindlimb locomotor activity, recorded SPN responses were increased in rostral (T4 - T7) compared to caudal (T8 - T11) segments. When locomotor-inducing neurochemicals were applied only to the lumbar region using a split-bath configuration, SPN population responses were increased in rostral (T4-7) but not caudal (T8-9) segments during both tonic and rhythmic VR activity. In both approaches, the greatest numbers of SPNs with increased fluorescence during rhythmic activity were in T6/7, whereas the greatest numbers with unchanged or decreased fluorescence were in caudal segments (T8-T11). Together these findings reveal a strong ascending lumbar to thoracic integrating communication pathway and may represent a key feature of spinal neural network function normally. Such communication pathways should be further investigated for targeted autonomic function(s) activation and therapeutic benefit after spinal cord injury.

Acute stress may disrupt decision - making by affecting cognitive and emotional processing. The behavioral and neural mechanisms of this in athletes are unclear. This study explored how acute stress impacts athletes unfairness - related decision - making and its neural basis. Forty participants (20 university athletes and 20 non - athlete students) were randomly assigned to a stress group or a control group. Using functional near - infrared spectroscopy (fNIRS), the study monitored the prefrontal cortex (PFC) and temporoparietal junction (TPJ) blood oxygenation during an ultimatum game task after inducing acute stress via the Maastricht Acute Stress Test (MAST). Athletes under stress were more accepting of relatively unfair decisions than non - athletes. This was linked to lower activation in the frontal - eye areas (CH15), supramarginal gyrus (CH38), and somatosensory association cortex (CH67), and higher activation in the primary motor cortex (CH64) in athletes. The increase in acceptance efficiency correlated significantly with the reduced CH38 activation (Rho = - 0.425) and increased CH64 activation (Rho = 0.499). Long - term exercise likely enhances PFC - TPJ functional integration, helping athletes adopt adaptive strategies under acute stress. These findings offer insights for developing stress management and neuromodulation training programs for athletes.

Spontaneous activity of neurons during early ontogenesis is instrumental for stabilization and refinement of developing neuronal connections. The role of spontaneous activity in synaptic development has been described in detail for cortical-like structures. Yet, very little is known about activity-dependent development of long-range inhibitory projections, such as projections from striatum. Here, we show that striatal projection neurons (SPNs) in dorsal striatum are spontaneously active in P4-P14 mice. Spontaneous activity was detected in both direct-pathway SPNs (dSPNs) and indirect-pathway SPNs (iSPNs). Most of the spontaneously active cells were in striosomes - a chemical compartment in striatum defined by expression of {micro}-opioid receptor. Higher excitability of both striosomal dSPNs and iSPNs was related to their intrinsic excitability properties (higher action potential half-width and IV slope). Tonic activation of muscarinic M1 receptor maintains the spontaneous activity of striosomal SPNs, the effect being stronger in iSPNs and weaker in dSPNs. To investigate if the neonatal spontaneous activity is needed for the stabilization of SPN long-range projections, we chemogenetically inhibited striosomal SPNs in neonatal animals and studied the efficiency of striatonigral projections in adult animals. Inhibition of striosomal SPNs by chronic CNO administration to P6-14 pups caused a reduction in the functional GABAergic innervation and in the density of gephyrin puncta in dopaminergic neurons of substantia nigra pars compacta of the adult (P52-79) animals. Chronic administration of CNO later in development (P21-29), on the contrary, resulted in higher mIPSC frequency in dopaminergic cells of the adult animals. Thus, the activity-dependent stabilization of striosomal projections has different developmental phases, and the long-term outcome of perturbations in these processes depends on the developmental period when they occur. Taken together, our results demonstrate that spontaneous activity of SPNs is essential for the maturation and stabilization of striatal efferents.

Although transcranial magnetic stimulation (TMS) research demonstrates that dorsal premotor cortex (PMd) influences neuroplasticity within primary motor cortex (M1), it is unclear how ageing modifies this communication. The present study investigated the influence of PMd on different indirect (I) wave inputs within M1 that mediate cortical plasticity in young and older adults. 15 young and 15 older participants completed two experimental sessions that examined the effects of intermittent theta burst stimulation (iTBS) to M1 when preceded by iTBS (PMd iTBS-M1 iTBS) or sham stimulation (PMd sham-M1 iTBS) to PMd. Changes in corticospinal excitability post-intervention were assessed with motor evoked potentials (MEP) recorded from right first dorsal interosseous using posterior-anterior (PA) and anterior-posterior (AP) current single-pulse TMS (PA1mV; AP1mV; PA0.5mV, early I-wave; AP0.5mV, late I-wave). Although PA1mV did not change post-intervention (P = 0.628), PMd iTBS-M1 iTBS disrupted the expected facilitation of AP1mV (to M1 iTBS) in young and older adults (P = 0.002). Similarly, PMd iTBS-M1 iTBS disrupted PA0.5mV facilitation in young and older adults (P = 0.030), whereas AP0.5mV facilitation was not affected in either group (P = 0.218). This suggests that while PMd specifically influences the plasticity of early I-wave circuits, this communication is preserved in older adults.

Microglia has been reported to be able to regulate the proliferation, differentiation and survival of adult Neural stem/progenitor cells (NSPCs) by modulating the microenvironment, which results in different consequences of adult neurogenesis. However, whether the microglial activation is beneficial or harmful to NSPCs is still controversial because of the complexity and variability of microglial activation phenotypes. In this study, we detected the expression levels of M1 marker and M2 marker in IFN-{gamma}- and IL-4-induced microglia at different time, respectively. The phenotypic markers of M1 and M2 microglia were stable for 24 h after removal of IFN-{gamma} and IL-4 intervention, but exhibited different change patterns during the next 24 h. Then, the adult NSPCs were treated by the conditioned medium from IFN-{gamma}- and IL-4-activated microglia. The conditioned medium from IFN-{gamma}-activated microglia promoted apoptosis and astroglial differentiation of NSPCs, while suppressed proliferation and neuronal differentiation of NSPCs. However, the conditioned medium from IL-4-activated microglia exhibited opposite effects on these physiological processes. In addition, the direct treatment of IFN-{gamma} or IL-4 alone did not significantly affect the proliferation, differentiation and survival of NSPCs. These results suggest that the secretome of pro-inflammatory (M1) and anti-inflammatory (M2) microglia differently regulated the proliferation, differentiation and survival of adult NSPCs. These findings will help further study the biological mechanism of microglia regulating neurogenesis, and provide a therapeutic strategy for neurological diseases by regulating microglial phenotypes to affect neurogenesis.

Associative memory, the ability to bind and retrieve relationships between unrelated elements, is a cornerstone of human cognition and a primary target for neurorehabilitation. Vagus nerve stimulation (VNS) has emerged as a promising method to modulate the locus coeruleus-norepinephrine (LC-NE) system and hippocampal-prefrontal circuits essential for memory. However, the comparative efficacy of non-invasive modalities such as electrical (E-taVNS) and the emerging field of ultrasound (U-taVNS) remains poorly understood in the context of active recall. In this study, participants performed a crossmodal video-word associative memory task before and after receiving either E-taVNS or U-taVNS in active and sham conditions. We investigated whether these modalities enhance cued recall accuracy and retrieval reaction time. Our results revealed that neither E-taVNS nor U-taVNS significantly improved recall accuracy. However, E-taVNS significantly accelerated response times specifically for correctly recalled items. These findings suggest that while taVNS may not increase the likelihood of recalling associative memories, electrical stimulation may enhances the efficiency in which we do so. These findings suggest that electrical taVNS is a viable tool for facilitating memory search processes, though further research is required to optimize ultrasound parameters and validate mechanistic pathways through physiological monitoring.

Glucose is a predominant fuel for the brain supporting its high energy demand associated with neuronal signaling and synaptic activity. Long-term potentiation (LTP) is required for learning and memory formation by generating long lasting increase in synaptic strength and signal transmission between two neurons. While the electrophysiological bases of LTP are well established, much less is known about the metabolic demands of neurons involved in LTP. Common protocols used to examine synaptic activity rely on high glucose concentrations which are far from physiological glucose levels found in the brain. Here we used primary hippocampal neurons cultured under physiological (2.5 mM) and high (25 mM) glucose to investigate the metabolic effects of chemically induced LTP. Physiological glucose was associated with neuronal survival while high glucose promoted "PAS granule" accumulation. Changes in glucose altered extracellular lactate and pyruvate concentrations and affected key intracellular metabolic intermediates and neurotransmitter levels in neuronal cells without depleting the TCA cycle. LTP induction was comparable, but mitochondrial and neurotransmitter response to LTP was differentially affected physiological and high glucose conditions. Glycogen phosphorylase inhibition had minimal effects in physiological glucose but impaired synaptic responses and altered metabolite dynamics in high glucose. Our findings demonstrate that neuronal mitochondrial metabolism is closely linked to synaptic plasticity and highlight the importance of studying neurophysiological activity physiologically relevant glucose conditions.

It is known that astrocytes, by the Ca2+-dependent release of gliotransmitters, which then act in pre- and post-synaptic receptors, modulate neuronal transmission and plasticity. Thus, hippocampal {theta}-burst long-term potentiation (LTP), which is a form of synaptic plasticity, can be modulated by astrocytes, since these cells release gliotransmitters that are crucial for the maintenance of LTP. Therefore, in this study, we hypothesized that the facilitatory action of BDNF upon LTP would involve astrocytes. To address that possibility, fEPSP recordings were performed in CA3-CA1 area of hippocampal slices from three different experimental models: Wistar rats where astrocytic metabolism was selectively reduced by a gliotoxin, the DL-fluoricitric acid (FC), IP3R2-/- mice, which lack IP3R2-mediated Ca2+-signaling in astrocytes and dn-SNARE transgenic mice, in which the SNARE-dependent release of gliotransmittersis impaired. For the three models we observed that the astrocytic impairment abolished the excitatory BDNF effect upon hippocampal LTP, only while inducing LTP with a mild {theta}-burst stimulation paradigm. The present data shows for the first time that astrocytes play an active role in the facilitatory action of BDNF upon LTP, depending on stimulation paradigm.

The internal microenvironment plays a critical role in the proliferation and differentiation of endogenous neural stem/progenitor cells (NSPCs). A big change in the spinal cord injury (SCI) microenvironment is the elevated level of glucocorticoids. In this study, we examined the impact of glucocorticoids on endogenous NSPCs in the adult mouse spinal cord. Our findings reveal that adult spinal cord NSPCs express glucocorticoid receptors, but not mineralocorticoid receptors. Glucocorticoids were found to significantly inhibit the proliferation and neurosphere formation of NSPCs via activation of glucocorticoid receptors, and they also impaired their differentiation. Importantly, the glucocorticoid receptor inhibitor CORT125281 was shown to enhance motor function in a traumatic SCI model in mice. Treatment with CORT125281 increased the number of NSPCs at the injury site in vivo. Flow cytometry and RNA sequencing analyses indicated that glucocorticoids induce NSPC arrest in the G1/G0 phase through the p53 signaling pathway. Glucocorticoids increased the expression of cell-cycle regulatory genes p15, p16, p18, and p27 in adult spinal cord NSPCs. In summary, our data suggest that glucocorticoids elevation following SCI suppresses the proliferation of endogenous NSPCs via glucocorticoid receptor activation. Targeting glucocorticoid receptors with specific inhibitors may represent a novel therapeutic strategy to promote recovery after spinal cord injury.

Cannabinoids are frequently used in the treatment of neuropathic pain related to nerve injury. However, despite evidence for their roles in the regulation of axonal guidance and synapse formation during development of the central nervous system (CNS), their possible involvement in response to peripheral nerve injury remains poorly defined and the knowledge of its role is mostly related to the peripheral sensory system. Following nerve injury, contemporary to axonal repair, massive morphological and functional changes reshape synaptic elements at neuromuscular junctions (NMJs) aiming to promote their reinnervation. This process is mediated in part by Perisynaptic Schwann cells (PSCs), glial cells at the NMJ essential for its maintenance and repair. Here we investigated the novel role of Cannabinoid type-1 receptor (CB1R) at NMJ, in particular on PSCs, during motor nerve recovery following nerve injury. Using morphological analysis, we studied the consequences of CB1R pharmacological and genetic blockade following denervation and reinnervation in adult NMJs. CB1R blockade caused an acceleration of the denervation process followed by a great delay in reinnervation as indicated by a significant percentage of denervated NMJs, accompanied by a decrease of mono- and poly-innervated NMJs. Remarkably, a similar phenomenon was observed when CB1R is selectively knocked-out in glia, indicating that the protective actions of these receptors are largely glia-dependent. These data highlight a novel role of the endocannabinoid system at NMJs, where the CB1Rs on PSCs can control NMJ denervation and reinnervation following nerve injury. A better understanding of the functional mechanisms underlying CB1R role in NMJ repair may contribute to finding a new pharmacological treatment having a dual role in improvements of motor recovery and in pain-related relief.

Hippocampus, a key hub of neural circuits for spatial learning and memory, has attracted tremendous studies. Neuronal information processing in the hippocampus can be regulated by many types of neuropeptides. Cholecystokinin (CCK), the most abundant neuropeptide in the central nervous system which is involved in modulating neuronal functions, such as cognition, memory and neuroplasticity, is widely expressed in the hippocampus. However, whether local excitatory CCK neurons modulates hippocampal function is still unclear. In this study, we showed that CA1 pyramidal neurons receive projections from excitatory CCK neurons in area CA3 (CA3CCK neurons). Subsequently, activation of the CA1-projecting CA3CCK neurons triggers the release of CCK. Then, we found that activity of CA3CCK-CA1 neurons supports the hippocampal-dependent tasks. Furthermore, inhibition of CA3CCK-CA1 projections or knockdown of CA3CCK gene expression markedly impaired the behavioral tasks and neuroplasticity. Taken together, these results may add to a better understanding of how neuromodulators regulate the neural functions in central nervous system.

Transcutaneous spinal cord stimulation (tSCS) of the cervical spinal cord has been thought to modulate lumbar networks, leading to the hypothesis that leg muscle recruitment may occur via recruitment of long-range spinal connections between cervical and lumbar circuits. To directly test this hypothesis, we compared arm and leg muscle responses elicited in unimpaired participants (N = 12) by cervical tSCS with the anodes placed over the iliac crests, with the anodes placed over the clavicles, and with lumbar tSCS as a control for leg muscle recruitment via the posterior root-muscle reflex. The idea of tSCS targeting cervico-lumbar connectivity would suggest that cervical stimulation could evoke responses in leg muscles. However, in our experiments, leg responses via cervical tSCS were only observed when the anodes were placed over the iliac crests, but not over the clavicles. These leg muscle responses had shorter latencies than those with lumbar tSCS and showed minimal post-activation depression, indicating efferent rather than afferent recruitment. Therefore, changes in leg muscle excitability by cervical-iliac tSCS previously attributed to descending cervical circuits could instead be explained by direct recruitment of efferent fibers near the iliac anodes. These findings suggest that cervical tSCS alone does not engage leg muscle motoneurons via long-range spinal or bidirectional pathways. Therefore, our study highlights the need to carefully consider electrode configuration when interpreting cervical tSCS mechanisms and additional or unexpected rehabilitative effects that extend caudally from the cervical spinal cord.

Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, e.g. wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic AChRs (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M4 and M1 mAChRs, respectively. At [~]1 mM ACh depolarized exclusively CT PCs via 4{beta}2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via 4{beta}2 nAChRs when the presynaptic neuron was a CT PC. Thus, in layer 6A the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening corticothalamic output while weakening corticocortical synaptic signaling.

Following spinal cord injury (SCI), intact neural resources undergo widespread reorganization within the brain. Animal models reveal motor cortical representations devoted to spared muscles above injury expand at the expense of territories occupied by weaker muscles. In this study, we investigated whether motor representations are similarly reorganized between a relatively spared biceps muscle and a weakened triceps muscle in persons with chronic tetraplegia following traumatic cervical SCI in association with upper limb motor function. Twenty-four adults with cervical SCI and 15 able-bodied participants underwent motor mapping using transcranial magnetic stimulation. We determined following map characteristics: area, amplitude (maximal motor evoked potential and volume), and center of gravity. Maximal voluntary contraction (MVC) and motor function (Capabilities of the Upper Extremity Test or CUE-T) were also assessed. Findings reveal that participants with SCI had hyper-excitable biceps maps than triceps, and hyper-excitable biceps maps also compared to biceps maps in able-bodied participants. Higher amplitude of biceps and triceps maps was associated with better motor function (higher CUE-T) and more distal injury (i.e., more spared segments) in persons with SCI. Amplitudes of biceps but not the triceps maps were associated with higher muscle MVCs. In conclusion, over-excitable biceps than triceps map in SCI may represent deafferentation plasticity. For the first time, we demonstrate how map reorganization of spared and weaker muscles in persons with chronic cervical SCI is associated with upper limb motor status. Use-dependent mechanisms may shift neural balance in favor of spared muscles, supporting potential use as response biomarkers in rehabilitation studies. New & NoteworthyOur study reports evidence in humans with cervical SCI that motor representation for the relatively spared muscle becomes hyper-excitable compared to that for the weaker muscle to the extent that hyper-excitability is even higher compared to biceps maps in uninjured individuals. Use-dependent mechanisms likely favor such heightened excitability of spared maps. For the first time, we demonstrate clinical relevance of map excitability in humans with SCI, supporting potential use as a biomarker of recovery.

Skeletal muscles are involved in responses to acute hypoxia as the largest organ in the body. However, as a hypoxic-tolerant tissue, responses in skeletal muscles caused by acute sedentary hypoxia are much less studied. We measured metabolites in skeletal muscles from mice exposed to 8% O2 for 0 minute, 15 minutes and 2 hours and studied the potential relationship between metabolite levels and mRNA levels by reconstructing genome-based metabolic networks and meta-analyzing differentially expressed genes acquired in skeletal muscles after 2 hours of 8% O2 exposure. The metabolite measurement indicated a significant increase in glutamine metabolism but not lactate metabolism in mouse skeletal muscles after 2 hours of hypoxia, where the metabolic responses as a whole were moderate. The central-dogma based metabolic flux analysis suggested an involvement of glutamine metabolism, though, as a whole, metabolite changes and gene changes didnt show a high correlation. Among metaoblites, glutamine metabolism indicated a significant response and a consistent change which could be interpreted by genome-based network analysis. In summary, though this study suggested a moderate metabolic response which has a weak correlation with gene expression change as a whole, glutamine metabolism indicated rapid responses in skeletal muscles responding to acute sedentary hypoxia.

Recent evidence suggests that myelin lipids may act as glial energy reserves when glucose is lacking, a hypothesis yet to be solidly proven. Hereby, we examined the effects of running a marathon on the myelin content by MRI. Our findings show that marathon runners undergo widespread robust myelin decrease at completion of the effort. This reduction involves white and gray matter, and includes primary motor and sensory cortical areas and pathways, as well as the entire corpus callosum and internal capsule. Notably, myelin levels partially recover within two weeks after the marathon. These results reveal that myelin use and replenishment is an unprecedented form of metabolic plasticity aimed to maintain brain function during extreme conditions. One-Sentence SummaryBrain myelin usage during strenuous exercise and recovery thereafter