Primary Motor Cortex Research Articles

Frontoparietal Structural Network Disconnections Correlate With Outcome After a Severe Stroke.

Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion-induced network disconnection and outcome after severe stroke. Thirty-eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow-up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region-to-region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3-6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location-specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke.

Anodal tDCS improves neuromuscular adaptations to short-term resistance training of the knee extensors in healthy individuals.

Experimental studies showed improvement in physical performance following acute application of transcranial direct current stimulation (tDCS). This study examined the neuromuscular and neural response to a single training session (Part 1) and after a 3-week resistance training (Part 2) performed with the knee extensors, preceded by tDCS over the primary motor cortex. Twenty-four participants (age, 30 ± 7 years; stature, 172 ± 8 cm; mass, 72 ± 15 kg) were randomly allocated to perform either resistance training with anodal tDCS (a-tDCS), or by a placebo tDCS (Sham). Resistance training consisted of 3 × 10 isometric contractions of 3 s at 75% MVC. Measures of neuromuscular function (MVC, voluntary activation and potentiated twitch force), corticospinal excitability, and short and long cortical inhibition were assessed. Acute tDCS did not affect neuromuscular and neural responses to a single training session (all ps ≥ 0.10). Conversely, after the 3-week training program, MVC increased in both groups (p < 0.01), with a greater increase observed for a-tDCS vs. Sham (⁓6%, p = 0.04). Additionally, increased voluntary activation (⁓2%, p = 0.04) and corticospinal excitability (⁓22%, p = 0.04), accompanied with shorter silent period (-13%, p = 0.04) was found following a-tDCS vs. Sham. The potentiated twitch force and measures of short and long cortical inhibition did not change after training programme (all ps ≥ 0.29). Pre-training administration of tDCS only resulted in greater neuromuscular adaptations following 3-weeks of resistance training. These results provide new evidence that tDCS facilitates adaptations to resistance training in healthy individuals.

Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current.

Sarcopenia, or pathological age-related loss of muscle strength and mass, contributes to physical function impairment in older adults. While current understanding of sarcopenia is centered mostly on neuromuscular mechanisms, mounting evidence supports that deficits at the level of the primary motor cortex (PMC) play a significant role. Despite the importance of the PMC to initiate movement, understanding of how age affects the excitability of layer V pyramidal neurons (LVPNs) of the PMC is limited. To address this, we used the whole-cell patch clamp technique to measure the excitability of LVPNs of the PMC in young, late adulthood, and old mice. Old LVPNs had increased firing frequency and membrane input resistance, but no differences in action potential kinetics versus young and late adulthood mice. Since changes in the persistent inward current (PIC) are known to contribute to changes in motor neuron excitability, we measured LVPN PICs as a putative contributor to LVPN excitability. The PIC amplitude was increased in old LVPN via increases in Na+ and Ca2+ PICs, in addition to being active across a wider voltage range. Given that LVPN function is integral to initiation of voluntary muscle contraction, altered LVPN excitability likely contributes to age-related impairment of physical function.

Syncing the brain’s networks: dynamic functional connectivity shifts from temporal interference

BackgroundTemporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex.Methods40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel’s intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC.ResultsFor CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P &amp;lt; 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P &amp;lt; 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P &amp;lt; 0.001). For mean dFC, a significant main effect of time was found (P &amp;lt; 0.001). TI–T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P &amp;lt; 0.001). Results were consistent across different window sizes.Conclusion20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex’s natural resonance.

Effects of puerarin on gait disturbance in a 6-hydroxydopamine mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine (DA) neuronal dysfunction. Although DA agonists and N-methyl-D-aspartate receptor (NMDAR) antagonists are used to treat PD, chronic use causes severe side effects. Puerarin (PUE) is a natural bioactive compound that affects the DA system; however, its effect on PD-associated motor functions is unknown. Therefore, we investigated whether PUE treatment in a 6-hydroxydopamine (6-OHDA) PD mouse model affects motor dysfunction. Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50mg/kg) or the vehicle (saline, VEH) was administered intraperitoneally once daily for 21 days. Motor dysfunction was assessed using the locomotion, gait cycle, and rotation tests. Local field potentials (LFPs) were measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex. 6-OHDA-lesioned PD mice showed increased gait cycle disturbance and unidirectional rotation. PUE treatment ameliorated the gait cycle disturbance, but not unidirectional rotation of PD mice. These effects differed with DA agonist treatment (which improved PD symptoms) and NMDAR antagonist treatment (which aggravated PD symptoms). Moreover, locomotion was increased only in NMDAR antagonist treatment. PUE treatment induced no changes in the attenuated LFP of the beta wave in the STR and STN, and SNc-STN delta-wave coherence was shown in PD animals. This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait cycle disturbance in PD symptoms.

Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS80), 90% (rTMS90) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEPMAX], slope and the intensity to evoke 50% MEPMAX), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Within LF-rTMS sessions, rTMS90, increased MEPMAX in the stimulated M1. Furthermore, rTMS90, increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants' baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS90 increased whereas rTMS80 decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. NCT02544503, NCT01726218.

Endogenous opioid receptor system mediates costly altruism in the human brain

Functional neuroimaging studies suggest that a large-scale brain network transforms others’ pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [11C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate’s pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others’ pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain.

Statistical method accounts for microscopic electric field distortions around neurons when simulating activation thresholds.

Notwithstanding advances in computational models of neuromodulation, there are mismatches between simulated and experimental activation thresholds. Transcranial Magnetic Stimulation (TMS) of the primary motor cortex generates motor evoked potentials (MEPs). At the threshold of MEP generation, whole-head models predict macroscopic (at millimeter scale) electric fields (50-70 V/m) which are considerably below conventionally simulated cortical neuron thresholds (200-300 V/m). We hypothesize that this apparent contradiction is in part a consequence of electrical field warping by brain microstructure. Classical neuronal models ignore the physical presence of neighboring neurons and microstructure and assume that the macroscopic field directly acts on the neurons. In previous work, we performed advanced numerical calculations considering realistic microscopic compartments (e.g., cells, blood vessels), resulting in locally inhomogeneous (micrometer scale) electric field and altered neuronal activation thresholds. Here we combine detailed neural threshold simulations under homogeneous field assumptions with microscopic field calculations, leveraging a novel statistical approach. We show that, provided brain-region specific microstructure metrics, a single statistically derived scaling factor between microscopic and macroscopic electric fields can be applied in predicting neuronal thresholds. For the cortical sample considered, the statistical methods match TMS experimental thresholds. Our approach can be broadly applied to neuromodulation models, where fully coupled microstructure scale simulations may not be practical.

Repetitive transcranial magnetic stimulation alleviates motor impairment in Parkinson’s disease: association with peripheral inflammatory regulatory T-cells and SYT6

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying the therapeutic effect of rTMS on Parkinson’s disease (PD) has not been fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears to be a key modulator of disease progression in PD. If rTMS affects the peripheral Tregs in PD remains unknown.MethodsHere, we conducted a prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 PD patients who received 10-day rTMS (10 Hz) stimulation on the primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well as flow cytology study were undertaken in 54 PD patients who were consecutively recruited from the department of neurology at Zhujiang hospital between September 2021 and January 2022. Subsequently, we implemented flow cytometry analysis to examine the Tregs population in spleen of MPTP-induced PD mice that received rTMS or sham treatment, along with quantitative proteomic approach reveal novel molecular targets for Parkinson's disease, and finally, the RNA interference method verifies the role of these new molecular targets in the treatment of PD.ResultsWe demonstrated that a 10-day rTMS treatment on the M1 motor cortex significantly improved motor dysfunction in PD patients. The beneficial effects persisted for up to 40 days, and were associated with an increase in peripheral Tregs. There was a positive correlation between Tregs and motor improvements in PD cases. Similarly, a 10-day rTMS treatment on the brains of MPTP-induced PD mice significantly ameliorated motor symptoms. rTMS reversed the downregulation of circulating Tregs and tyrosine hydroxylase neurons in these mice. It also increased anti-inflammatory mediators, deactivated microglia, and decreased inflammatory cytokines. These effects were blocked by administration of a Treg inhibitor anti-CD25 antibody in MPTP-induced PD mice. Quantitative proteomic analysis identified TLR4, TH, Slc6a3 and especially Syt6 as the hub node proteins related to Tregs and rTMS therapy. Lastly, we validated the role of Treg and rTMS-related protein syt6 in MPTP mice using the virus interference method.ConclusionsOur clinical and experimental studies suggest that rTMS improves motor function by modulating the function of Tregs and suppressing toxic neuroinflammation. Hub node proteins (especially Syt6) may be potential therapeutic targets.Trial registrationChinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691Graphical rTMS is a safe and non-invasive method for Parkinson's disease. In this study, we showed the proportion of CD4+CD25+CD127- regulatory T-cells (Tregs) in the peripheral blood was significantly increased after rTMS treatment. Similar effects of rTMS treatment were verified in MPTP-induced PD mice. Proteomic analysis and RNA interference analyses identified TLR4, TH, Slc6a3 and especially Syt6 as hub node proteins that can be modulated by rTMS therapy in PD.

Structural Covariance Networks in the Fetal Brain Reveal Altered Neurodevelopment for Specific Subtypes of Congenital Heart Disease.

Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics. We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra-axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester. Structural covariance networks offer a sensitive, data-driven approach to explore whole-brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

Laminar fMRI in the locked-in stage of amyotrophic lateral sclerosis shows preserved activity in layer Vb of primary motor cortex

Amyotrophic lateral sclerosis (ALS) affects the cerebral cortex layer-dependently, most notably by the foremost targeting of upper motor neurons (UMNs) sited in layer Vb. Previous studies have shown a retained ability of paralysed patients to activate cortical motor networks, even in late-stage ALS. However, it is currently unknown whether such activation reflects a retained capacity to process sensorimotor inputs or if it is a result of actual motor output. Given the distinct function of individual cortical layers, layer-specific functional measurements may provide insight to this question. In this study, using submillimetre resolution laminar fMRI, we assessed the layer-dependent activation associated with attempted (motor) and passive (somatosensory) movements in a locked-in stage ALS patient. We found robust activation in both superficial and deep layers of primary motor cortex (M1). The peak activation in deep layers was localised to layer Vb. These findings demonstrate preserved activity in deep output layers of M1, possibly reflecting a retained ability to engage surviving UMNs despite years of paralysis. Our study underscores the capacity of laminar fMRI to discern subtle cortical activity and elucidates a promising pathway for probing in vivo human ALS pathology with unprecedented resolution.

Coupling of Slow Oscillations in the Prefrontal and Motor Cortex Predicts Onset of Spindle Trains and Persistent Memory Reactivations.

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.

Effects of Continuous Theta Burst Stimulation on Contralateral Primary Motor Cortex: A Concurrent TMS-EEG Study.

Continuous theta burst stimulation (cTBS) is a non-invasive brain stimulation technique. cTBS modulation is an effective treatment for motor dysfunction rehabilitation in post-stroke patients. However, there's currently a lack of research on the effects of cTBS stimulation on the contralesional hemisphere. To better understand the role of cTBS in motor rehabilitation, we investigated the neuroregulatory mechanisms of cTBS in the contralateral cortex using transcranial magnetic stimulation-evoked electroencephalography (TMS-EEG). In this randomized, sham-controlled, single-blind study, 18 healthy subjects received two separate stimulation conditions:cTBS or sham stimulation applied to the left M1. TMS-EEG measurements were taken before and immediately after stimulation. We investigated the TMS-evoked potentials (TEPs), evoked oscillatory responses (EOR), and phase synchronization index(PSI) of TMS-EEG. The effects of cTBS were analyzed using two-way repeated measures analysis of variance (RMANOVA). There was a significant "cTBS condition×time" interaction effect on the theta and gamma bands of EOR, as well as on inter-hemisphere PSI (inter-PSI) and global PSI in both cTBS stimulation conditions. (theta:F=4.526,p=0.041;gamma:F=5.574,p=0.024;inter-PSI:F=5.028,p=0.032;global PSI:F=5.129,p=0.030).After real cTBS modulation, the energy in the theta and gamma frequency bands was significantly higher than before (theta: F=5.747, p=0.022; gamma: F=5.545, p=0.024). The inter-PSI and global PSI significantly increased after real cTBS modulation (inter-PSI: F=6.209, p=0.018; global PSI: F=6.530, p=0.015). cTBS modulation significantly increased EOR and PSI in contralateral brain regions, thereby enhancing cortical excitability and cortical functional connectivity throughout the brain. This provides a theoretical basis for cTBS neuromodulation in stroke patients.

Meta-learning of human motor adaptation via the dorsal premotor cortex

Meta-learning enables us to learn how to learn the same or similar tasks more efficiently. Decision-making literature theorizes that a prefrontal network, including the orbitofrontal and anterior cingulate cortices, underlies meta-learning of decision making by reinforcement learning. Recently, computationally similar meta-learning has been theorized and empirically demonstrated in motor adaptation. However, it remains unclear whether meta-learning of motor adaptation also relies on a prefrontal network. Considering hierarchical information flow from the prefrontal to motor cortices, this study explores whether meta-learning is processed in the dorsolateral prefrontal cortex (DLPFC) or in the dorsal premotor cortex (PMd), which is situated upstream of the primary motor cortex, but downstream of the DLPFC. Transcranial magnetic stimulation (TMS) was delivered to either PMd or DLPFC during a motor meta-learning task, in which human participants were trained to regulate the rate and retention of motor adaptation to maximize rewards. While motor adaptation itself was intact, TMS to PMd, but not DLPFC, attenuated meta-learning, impairing the ability to regulate motor adaptation to maximize rewards. Further analyses revealed that TMS to PMd attenuated meta-learning of memory retention. These results suggest that meta-learning of motor adaptation relies more on the premotor area than on a prefrontal network. Thus, while PMd is traditionally viewed as crucial for planning motor actions, this study suggests that PMd is also crucial for meta-learning of motor adaptation, processing goal-directed planning of how long motor memory should be retained to fit the long-term goal of motor adaptation.

Neuromodulation Effect According to Lesion Location After Dual-Mode Brain Stimulation in Patients with Subacute Stroke: A Preliminary Study

Dual-mode non-invasive brain stimulation using repetitive transcranial magnetic stimulation and transcranial direct current stimulation is known to help neurorehabilitation in patients with stroke. However, this neuromodulation effect may vary depending on the lesion location of patients with stroke, and the basis in lesion location for this is insufficient. This study aims to investigate the difference in neuromodulation effectiveness according to the lesion location after dual-mode brain stimulation using electroencephalography signals. Eight patients with ischemic subacute stroke and 11 healthy controls participated in this study. Brain stimulation was conducted in one session per day for a total of 10 days over the motor cortex, electroencephalography was measured for 5 min with eyes closed, and motor function was evaluated before and after dual-mode stimulation. The lesion location was divided into an infratentorial stroke (ITS) and a supratentorial stroke (STS) based on tentorium cerebelli. In addition, we focused on the mu and beta bands related to motor function. In terms of intrahemispheric connectivity, the mu weighted phase lag index over the contralesional primary motor cortex was significantly higher in only ITS before stimulation compared to healthy controls, and mu Granger causality over the ipsilesional primary motor cortex was significantly higher in both ITS and STS after stimulation compared to healthy controls. In contrast, from the perspective of interhemispheric connectivity, the laterality of beta Granger causality before stimulation in ITS was lower than that of healthy controls and significantly increased after stimulation. The effect of brain stimulation may vary depending on the lesion location of patients with stroke, and these findings provide indicative insights into effective dual-mode stimulation interventions for neurorehabilitation.

An ANN models cortical-subcortical interaction during post-stroke recovery of finger dexterity.

Finger dexterity, and finger individuation in particular, is crucial for human movement, and disruptions due to brain injury can significantly impact quality of life. Understanding the neurological mechanisms responsible for recovery is vital for effective neurorehabilitation. This study explores the role of two key pathways in finger individuation: the corticospinal tract (CST) from the primary motor cortex and premotor areas, and the subcortical reticulospinal tract (RST) from the brainstem. We aimed to investigate how the cortical-reticular network reorganizes to aid recovery of finger dexterity following lesions in these areas. To provide a potential biologically plausible answer to this question, we developed an artificial neural network (ANN) to model the interaction between a premotor planning layer, a cortical layer with excitatory and inhibitory corticospinal outputs, and reticulospinal outputs controlling finger movements. The ANN was trained to simulate normal finger individuation and strength. A simulated stroke was then applied to the corticospinal (CS) area, reticulospinal (RS) area, or both, and the recovery of finger dexterity was analyzed. In the intact model, the ANN demonstrated a near-linear relationship between the forces of instructed and uninstructed fingers, resembling human individuation patterns. Post-stroke simulations revealed that lesions in both CS and RS regions led to increased unintended force in uninstructed fingers, immediate weakening of instructed fingers, improved control during early recovery, and increased neural plasticity. Lesions in the CS region alone significantly impaired individuation, while RS lesions affected strength and to a lesser extent, individuation. The model also predicted the impact of stroke severity on finger individuation, highlighting the combined effects of CS and RS lesions. This model provides insights into the interactive role of cortical and subcortical regions in finger individuation. It suggests that recovery mechanisms involve reorganization of these networks, which may inform neurorehabilitation strategies.

Comparing the effects of anodal and cathodal transcranial direct current stimulation of primary motor cortex at varying intensities on motor learning in healthy young adults.

Inconsistent results are observed in the effects of transcranial direct current stimulation (tDCS) with different montages on motor learning. This study aimed to compare the effects of anodal and cathodal tDCS (c-tDCS) over primary motor cortex (M1) at different intensities on motor learning in healthy young adults. The participants were randomly divided into: (1) 1mA M1 c-tDCS, (2) 1mA M1 anodal tDCS (a-tDCS), (3) 2mA M1 c-tDCS, (4) 2mA M1 a-tDCS and (5) M1 sham tDCS groups. The groups received 20-min stimulation with serial reaction time task (SRTT) incidentally, while the tDCS was turned off after 30 s in the sham tDCS group. Response time (RT) and error rate (ER) during SRTT were assessed prior, during and 72 h after the intervention. The results of the paired t-test indicated that online learning occurred in all groups (p< 0.05), except in M1 c-tDCS (1mA) (p> 0.05). One-way ANOVA analysis also indicated that there were differences in offline learning (RT (F(DF) =5.19(4); p< 0.001; and ER (F(DF) =9(4), p< 0.0001) among groups, with more offline learning in 1mA M1 a-tDCS, 2mA M1 c-tDCS and 2mA M1 a-tDCS groups (p< 0.05). On the other hand, the 1mA M1 c-tDCS group did not indicate any consolidation effect or even a trend toward negative offline learning. M1 a-tDCS with different intensities and also 2mA M1 c-tDCS may be helpful for the enhancement of motor learning in young healthy adults. This study enhances our understanding of tDCS intensity and polarity effects on motor learning, with potential for optimizing therapeutic protocols.

Dorsolateral prefrontal cortex to ipsilateral primary motor cortex intercortical interactions during inhibitory control enhance response inhibition in open-skill athletes

Numerous studies have reported that long-term sports training can affect inhibitory control and induce brain functional alterations. However, the influence of environmental dynamics in sports training on inter-cortical connectivity has not been well studied. In the current study, we used twin-coil transcranial magnetic stimulation to investigate the functional connectivity between dorsolateral prefrontal cortex (DLPFC) and ipsilateral primary motor cortex (M1) during proactive and reactive inhibition in participants with sports skills in dynamic environment (open-skill experts), stable environment (closed-skill experts), and no sports skills (controls). Using a modified stop signal task, proactive inhibition was measured by the response delay effect (RDE), and reactive inhibition was measured by the stop-signal reaction time (SSRT). Intra-hemispheric DLPFC-M1 interactions and single pulse motor-evoked potentials (MEPs) were measured during the task. A stronger inhibitory effect of the DLPFC over M1 was observed during early reactive control stages compared to baseline levels. In addition, this inhibitory effect was pronounced when comparing open-skill experts to non-athlete controls, a relationship that was significantly correlated with superior reactive control performance. Furthermore, DLPFC to M1 influencing direction shifted from late proactive control to reactive control. Behavioral results also demonstrated enhanced proactive control abilities in open-skill experts relative to controls. Such enhancement may be due to the combination of environmental complexity and physical fitness in long-term skill training.

The corticospinal tract in multiple sclerosis: correlation between cortical excitability and magnetic resonance imaging measures.

Multiple sclerosis (MS) is a central nervous system disease involving gray and white matters. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) could help identify potential markers of disease evolution, disability, and treatment response. This work evaluates the relationship between intracortical inhibition and facilitation, motor cortex lesions, and corticospinal tract (CST) integrity. Consecutive adult patients with progressive MS were included. Sociodemographic and clinical data were collected. MRI was acquired to assess primary motor cortex lesions (double inversion and phase-sensitive inversion recovery) and CST integrity (diffusion tensor imaging). TMS outcomes were obtained: motor evoked potentials (MEP) latency, resting motor threshold, short-interval intracortical facilitation (ICF) and inhibition. Correlation analysis was performed. Twenty-five patients completed the study (13 females, age: 55.60 ± 11.49 years, Expanded Disability Status Score: 6.00 ± 1.25). Inverse correlations were found between ICF mean and each of CST radial diffusivity (RD) (ρ =-0.56; p < 0.01), CST apparent diffusion coefficient (ADC) (ρ=-0.44; p = 0.03), and disease duration (ρ=-0.46; p = 0.02). MEP latencies were directly correlated with disability scores (ρ = 0.55; p < 0.01). High ADC/RD and low ICF have been previously reported in patients with MS. While the former could reflect structural damage of the CST, the latter could hint towards an aberrant synaptic transmission as well as a depletion of facilitatory compensatory mechanisms that helps overcoming functional decline. The findings suggest concomitant structural and functional abnormalities at later disease stages that would be accompanied with a heightened disability. The results should be interpreted with caution mainly because of the small sample size that precludes further comparisons (e.g., treated vs. untreated patients, primary vs. secondary progressive MS). The role of these outcomes as potential MS biomarkers merit to be further explored.

Methodological Choices Matter: A Systematic Comparison of TMS-EEG Studies Targeting the Primary Motor Cortex.

Transcranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared specific TEP peaks and components between studies using distinct methods. Reporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and preprocessing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the "prototypical" TEP waveform following stimulation of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long-latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP magnitudes. In summary, some aspects of reporting practices could be improved in future TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted.