Search Results (12)

Excitatory–inhibitory (E-I) local circuits play a central role in synaptic plasticity and neural coding, yet their multilayer learning dynamics remain poorly understood. We constructed a multilayer feedforward spiking neural network with intra-layer E-I connectivity, using Izhikevich neurons to model regular spiking (RS) and fast spiking (FS) cells, and examined cooperative learning under excitatory and inhibitory spike-timing-dependent plasticity (eSTDP and iSTDP). FS-mediated lateral inhibition alleviates the long-term depression bias arising from RS firing rate adaptation via winner-take-all competition, promoting heterogeneous E→E weight differentiation while preserving mean synaptic strength. A $12\times 12$ parameter grid scan shows that iSTDP expands the stable learning region in the E-I parameter space and reveals a sustained cooperative co-evolution of eSTDP and iSTDP during training. For sparse coding, RS adaptation is the primary driver of Lifetime Sparseness, with FS inhibition acting as a cooperative enhancer; the network exhibits low sparseness at the input layer, a rapid increase at the second layer, and a stable plateau in deeper layers. For temporal pattern learning, the selectivity index $d^{\prime }$ improved substantially after training, reaching approximately 1.90 times that of the FS-absent condition; both interval sensitivity and pattern generalization tests confirmed that this advantage is robust across biologically plausible inter-group delays and preserved under small temporal jitter. Mutual information analysis reveals a consistent tendency for intra-layer FS circuits to maintain higher stimulus-related information across deep layers, consistent with FS-mediated suppression of non-specific responses. These findings provide computational evidence, within the scope of the present model, for understanding cortical E-I cooperative plasticity and inform design principles for neuromorphic systems with adaptive inhibitory regulation. Full article

Background/Aim: Motor skill acquisition is the foundation of athletic performance, from the novice learning a new technique to the elite athlete executing complex movements automatically under pressure. Although classical models have defined the neural substrates of motor control—the cerebellum for error correction, the basal ganglia for action selection, and the primary motor cortex (M1) for execution—emerging evidence suggests that motor learning is the result of the dynamic interaction of multiple parallel processes rather than a linear hierarchy. This narrative review integrates classical neuroanatomical knowledge with contemporary findings on multisite plasticity, with a particular focus on sport-specific adaptations. Methods: We examined three core learning mechanisms operating in parallel: error-based learning (cerebellar-dependent, driven by sensory prediction errors), reinforcement learning (striatal-dependent, driven by reward prediction errors and dopamine), and use-dependent learning (cortical-dependent, driven by mere repetition). We also summarize the biochemical pathways supporting these learning processes, including glutamatergic LTP-like cortical plasticity, cerebellar mGluR1–PKC–LTD signaling, dopaminergic corticostriatal plasticity, BDNF–TrkB-dependent neurotrophic mechanisms, growth-factor signaling, and exercise-induced muscle–brain communication. Results: We then propose a spatiotemporal model in which the relative contribution of each network shifts dynamically across the three stages of skill acquisition, from the early cognitive/strategic phase to the late automatic phase characteristic of elite performance. At the molecular level, these stage-dependent adaptations are supported by synaptic strengthening and weakening mechanisms, reward-dependent dopamine signaling, neurotrophic and growth-factor-mediated remodeling, and peripheral metabolic/myokine signals that modulate brain plasticity during training and recovery. Special attention is given to contextual and sport-specific adaptations, using the paradigmatic example of elite swimmers who demonstrate enhanced short-interval intracortical inhibition (SICI) selectively in the aquatic environment, reflecting long-term sport-induced neuroplasticity. Conclusions: Understanding these dynamic network mechanisms has direct implications for coaching, training periodization, and the development of targeted neuromodulatory interventions to accelerate skill acquisition and optimize athletic performance. Full article

Background/Objectives: Upper-limb motor dysfunction is common after stroke, and patients often have limited recovery during rehabilitation. In this study, we aimed to investigate the relationship between contralesional neurophysiological parameters and the effects of rehabilitation on upper-limb motor function in stroke patients with corticospinal tract damage. Methods: Forty patients with subacute stroke with an absent MEP response on the ipsilesional side before admission were included. Contralesional neurophysiological parameters, including resting motor threshold, contralesional MEP, contralesional short-interval intracortical inhibition (short-ICI), and contralesional long-interval intracortical inhibition (long-ICI), were assessed via transcranial magnetic stimulation (TMS) pre-admission. The coefficients of variation for MEP, short-ICI, and long-ICI were calculated to assess cortical stability. Rehabilitation effect was measured using changes in the Fugl–Meyer assessment score after 21 days of rehabilitation. Results: No single contralesional parameter significantly predicted rehabilitation effect. Further exploratory analysis revealed that a model combining contralesional neurophysiological parameters was associated with proximal limb motor function recovery. Short-ICI played a prominent role in this exploratory model. Conclusions: Contralesional neurophysiological markers demonstrated limited predictive value in patients with stroke with moderate-to-severe motor dysfunction and damaged corticospinal tract function on the ipsilesional side. However, a model combining multimodal contralesional TMS measures, particularly short-ICI, may offer incremental value in predicting proximal limb motor improvement following 21-day rehabilitation. Although this mechanism was not directly measured, the findings suggest a compensatory role of the cortico-reticulo-spinal pathway. These exploratory results should be interpreted with caution regarding their clinical applicability and are premature as a predictive tool, pending rigorous external validation. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Objectives: Sports-related concussion (SRC) is mostly associated with contact and combat sports. However, emerging evidence suggest that cyclists are also at risk of repeated concussion injury. Moreover, long-term neurophysiological outcomes in cycling cohorts remain underexplored. This novel study investigated the long-term effect of repetitive concussions in cyclists. Road, mountain biking (MTB), and BMX riders with a history of concussions and self-reported persistent symptoms were assess for neurophysiology and cognitive–motor performance compared to previously concussed cyclists with no ongoing symptoms. Both groups were compared to age-matched with controls. Methods: Using a cross-sectional between-group design, 25 cyclists with a history of concussions (15 symptomatic, 10 asymptomatic) and 20 controls completed symptom reporting, cognitive and balance assessments (SCAT5), sensorimotor testing using vibrotactile stimulation, and neurophysiological assessments via transcranial magnetic stimulation (TMS). Results: Symptomatic cyclists reported a higher number of concussions compared to asymptomatic cyclists (p = 0.041). Cognitive testing revealed large effects (d > 1.0), with impaired concentration in symptomatic cyclists compared to controls (p = 0.005). Motor assessments demonstrated large effects (d > 1.0), with slower tandem gait times (p < 0.001) and greater errors (p = 0.02) in the symptomatic group. Sensorimotor testing indicated slowed simple reaction times (p = 0.001) and poorer temporal order judgement (p = 0.038). TMS showed large effects (d > 1.0) in increased cortical inhibition in the symptomatic group, with prolong cortical silent periods (p < 0.05) and large effects (d > 1.0), and reduced short interval intracortical inhibition (p = 0.001) compared to asymptomatic cyclists and controls. Conclusions: Cyclists reporting persistent symptoms showed greater cortical inhibition and impaired cognitive–motor performance, consistent with findings in contact sport athletes. These results suggest that repeated concussions in cycling carry risk of chronic neurophysiological alterations. Cycling disciplines should consider more rigorous concussion identification protocols and stricter management strategies to mitigate persistent and long-term consequences. Full article

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. Methods: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. Results: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians’ diagnostic confidence when TMS data were incorporated. Conclusions: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability. Full article

Paired associative stimulation (PAS) increases and decreases cortical excitability in primary motor cortex (M1) neurons, depending on the spike timing-dependent plasticity, i.e., long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity, respectively. However, how PAS affects the cortical circuits for the agonist and antagonist muscles of M1 is unclear. Here, we investigated the changes in the LTP- and LTD-like plasticity for agonist and antagonist muscles during PAS: 200 pairs of 0.25-Hz peripheral electric stimulation of the right median nerve at the wrist, followed by a transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 ms (PAS-25 ms) and 10 ms (PAS-10 ms). The unconditioned motor evoked potential amplitudes of the agonist muscles were larger after PAS-25 ms than after PAS-10 ms, while those of the antagonist muscles were smaller after PAS-25 ms than after PAS-10 ms. The γ-aminobutyric acid A (GABA_A)- and GABA_B-mediated cortical inhibition for the agonist and antagonist muscles were higher after PAS-25 ms than after PAS-10 ms. The cortical excitability for the agonist and antagonist muscles reciprocally and topographically increased and decreased after PAS, respectively; however, GABA_A and GABA_B-mediated cortical inhibitory functions for the agonist and antagonist muscles were less topographically decreased after PAS-10 ms. Thus, PAS-25 ms and PAS-10 ms differentially affect the LTP- and LTD-like plasticity in agonist and antagonist muscles. Full article

Background: The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABA_B)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths. Methods: We analyzed data from three previous studies of youth who underwent CSP and LICI measurements with transcranial magnetic stimulation and electromyography. We assessed CSP and LICI association using Spearman rank correlation tests and multiple linear regression analyses adjusted for demographic and clinical covariates. Results: The sample included 16 healthy participants and 45 participants with depression. The general mean (SD) age was 15.5 (1.7), 14.3 (1.7) for healthy participants, and 15.9 (1.6) years for participants with depression. Measures were nonnormally distributed (Shapiro–Wilk, p < 0.001). CSP and LICI were not correlated at 100-millisecond (ρ = −0.2421, p = 0.06), 150-millisecond (ρ = −0.1612, p = 0.21), or 200-millisecond (ρ = −0.0507, p = 0.70) interstimulus intervals using Spearman rank correlation test. No correlations were found in the multiple regression analysis (p = 0.35). Conclusions: Although previous studies suggest that cortical silent period and long-interval intracortical inhibition measure GABA_B receptor-mediated activity, these biomarkers were not associated in our sample of youths. Future studies should focus on the specific physiologic and pharmacodynamic properties assessed by CSP and LICI in younger populations. Full article

Paired associative stimulation (PAS) is a stimulation technique combining transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) that can induce plastic changes in the human motor system. A PAS protocol consisting of a high-intensity single TMS pulse given at 100% of stimulator output (SO) and high-frequency 100-Hz PNS train, or “the high-PAS” was designed to promote corticomotoneuronal synapses. Such PAS, applied as a long-term intervention, has demonstrated therapeutic efficacy in spinal cord injury (SCI) patients. Adding a second TMS pulse, however, rendered this protocol inhibitory. The current study sought for more effective PAS parameters. Here, we added a third TMS pulse, i.e., a 20-Hz rTMS (three pulses at 96% SO) combined with high-frequency PNS (six pulses at 100 Hz). We examined the ability of the proposed stimulation paradigm to induce the potentiation of motor-evoked potentials (MEPs) in five human subjects and described the safety and tolerability of the new protocol in these subjects. In this study, rTMS alone was used as a control. In addition, we compared the efficacy of the new protocol in five subjects with two PAS protocols consisting of PNS trains of six pulses at 100 Hz combined with (a) single 100% SO TMS pulses (high-PAS) and (b) a 20-Hz rTMS at a lower intensity (three pulses at 120% RMT). The MEPs were measured immediately after, and 30 and 60 min after the stimulation. Although at 0 and 30 min there was no significant difference in the induced MEP potentiation between the new PAS protocol and the rTMS control, the MEP potentiation remained significantly higher at 60 min after the new PAS than after rTMS alone. At 60 min, the new protocol was also more effective than the two other PAS protocols. The new protocol caused strong involuntary twitches in three subjects and, therefore, its further characterization is needed before introducing it for clinical research. Additionally, its mechanism plausibly differs from PAS with high-frequency PNS that has been used in SCI patients. Full article

Chronic pain syndromes present a subversion of both functional and structural nociceptive networks. We used transcranial magnetic stimulation (TMS) to evaluate changes in cortical excitability and plasticity in patients with chronic migraine (CM) treated with botulinum neurotoxin type A (BoNT/A). We enrolled 11 patients with episodic migraine (EM) and 11 affected by CM. Baseline characteristics for both groups were recorded using single- and paired-pulse TMS protocols. The same TMS protocol was repeated in CM patients after four cycles of BoNT/A completed in one year. At baseline, compared with EM patients, patients with CM had a lower threshold in both hemispheres (right hemisphere: 46% ± 7.8 vs. 52% ± 4.28, p = 0.03; left hemisphere: 52% ± 4.28 vs. 53.54% ± 6.58, p = 0.02). In EM, paired-pulse stimulation elicited a physiologically shaped response, whereas in CM, physiological intracortical inhibition (ICI) between 1 and 3 ms intervals was absent at baseline. On the contrary, increasing intracortical facilitation (ICF) was observed for all interstimulus intervals (ISIs). In CM, cortical excitability was partially reduced after BoNT/A treatment, along with a significant decrease observed in MIDAS score (from 20.7 to 9.8; p = 0.008). The lower motor threshold in CM reflects a higher cortical hyperexcitability. The lack of physiological ICI in CM could indicate sensitisation of the trigeminovascular system. Although reduced, this type of response is still observable after treatment, despite a marked clinical improvement. Our study suggests a long-term alteration of cortical plasticity due to chronic pain. Full article

The Met allele of the brain-derived neurotrophic factor (BDNF) gene confers reduced cortical BDNF expression and associated neurobehavioral changes. BDNF signaling influences the survival, development, and synaptic function of cortical networks. Here, we compared gamma-aminobutyric acid (GABA)ergic network activity in the human primary motor cortex (M1) between the Met (Val/Met and Met/Met) and non-Met (Val/Val) genotype groups. Short- and long-interval intracortical inhibition, short-latency afferent inhibition (SAI), and long-latency afferent inhibition were measured using transcranial magnetic stimulation (TMS) as indices of GABAergic activity. Furthermore, the considerable inter-individual variability in inhibitory network activity typically measured by TMS may be affected not only by GABA but also by other pathways, including glutamatergic and cholinergic activities; therefore, we used 3-T magnetic resonance spectroscopy (MRS) to measure the dynamics of glutamate plus glutamine (Glx) and choline concentrations in the left M1, left somatosensory cortex, and right cerebellum. All inhibitory TMS conditions produced significantly smaller motor-evoked potentials than single-pulses. SAI was significantly stronger in the Met group than in the Val/Val group. Only the M1 Glx concentration was significantly lower in the Met group, while the BDNF genotype did not affect choline concentration in any region. Further, a positive correlation was observed between SAI and Glx concentrations only in M1. Our findings provide evidence that the BDNF genotype regulates both the inhibitory and excitatory circuits in human M1. In addition, lower Glx concentration in the M1 of Met carriers may alter specific inhibitory network on M1, thereby influencing the cortical signal processing required for neurobehavioral functions. Full article

We aimed to verify whether indirect-wave (I-wave) recruitment and cortical inhibition can regulate or predict the plastic response to paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), and also whether water immersion (WI) can facilitate the subsequent PAS25-induced plasticity. To address the first question, we applied transcranial magnetic stimulation (TMS) to the M1 hand area, while alternating the direction of the induced current between posterior-to-anterior and anterior-to-posterior to activate two independent synaptic inputs to the corticospinal neurons. Moreover, we used a paired stimulation paradigm to evaluate the short-latency afferent inhibition (SAI) and short-interval intracortical inhibition (SICI). To address the second question, we examined the motor evoked potential (MEP) amplitudes before and after PAS25, with and without WI, and used the SAI, SICI, and MEP recruitment curves to determine the mechanism underlying priming by WI on PAS25. We demonstrated that SAI, with an inter-stimulus interval of 25 ms, might serve as a predictor of the response to PAS25, whereas I-wave recruitment evaluated by the MEP latency difference was not predictive of the PAS25 response, and found that 15 min WI prior to PAS25 facilitated long-term potentiation (LTP)-like plasticity due to a homeostatic increase in cholinergic activity. Full article