Search Results (120)

Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke patients with ataxic symptoms, to follow up on changes in motor function and balance due to recovery and rehabilitation, and to investigate the different effects of two treatment methods on neuronal plasticity. Methods: Therefore, fMRI-paradigms foot tapping and the motor imagery (MI) of a balancing task (tandem walking) were employed. Results: The paradigms investigated were suitable for ataxic stroke patients to monitor changes in neuroplasticity while revealing increased activity in the primary motor cortex (M1) and the cerebellum over 3 months of treatment. Furthermore, analysis of the more complex balance task revealed augmented activation of association areas due to training. Coordination exercises, constituting a specific treatment of ataxic symptoms, indicate more consolidated brain activations, corresponding to a faster motor learning process. Activation within Brodmann Area 7 has been prominent among all paradigms, indicating a special importance of this region for coordinative functions. Conclusions: Further studies are needed to confirm our results in larger patient groups. Clinical Trial Registration: German Clinical Trials Registry (drks.de). Identifier: DRKS00020825. Registered 16.07.2020. Full article

Background: Chronic shoulder pain is a prevalent musculoskeletal disorder often associated with central sensitisation, which limits the effectiveness of conventional therapies. Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuromodulatory intervention to modulate cortical excitability and potentially improve pain and functional outcomes. Methods: This scoping review followed the Joanna Briggs Institute (JBI) framework and PRISMA-ScR guidelines. A systematic search was conducted across MEDLINE, CENTRAL, Scopus, PEDro, and Web of Science to identify studies evaluating the effects of tDCS on pain and function in adults with rotator cuff disorders, myofascial pain syndrome (MPS), or subacromial pain syndrome (SAPS). Data were extracted and synthesised qualitatively. Results: Four studies met the inclusion criteria. tDCS demonstrated variable efficacy: some trials reported no additional benefit when used alongside corticosteroid injections or sensorimotor training (e.g., SAPS and rotator cuff tendinopathy), while others showed enhanced pain reduction and functional gains, particularly in MPS. Targeting the dorsolateral prefrontal cortex (DLPFC) appeared more effective than stimulating the primary motor cortex (M1) in modulating pain. Functional improvements were generally observed, though not consistently superior to sham interventions. Conclusions: Preliminary evidence suggests that tDCS may represent a promising adjunctive treatment for chronic shoulder pain, particularly in MPS. However, due to the limited number of studies and heterogeneity in methods, conclusions should be interpreted with caution. However, heterogeneity in study protocols, stimulation targets, and patient populations limits conclusive recommendations. Standardised protocols and larger trials are needed to determine the optimal application of tDCS in clinical shoulder pain management. Full article

Background: Falls among the elderly present significant physical, psychological, and economic challenges. Fall prevention strategies, such as balance and muscle strengthening exercises, are essential but often require long-term commitment. This study explores the potential of transcranial direct current stimulation (tDCS) as an adjunct to balance training to enhance physical performance in the elderly. Method: A randomized, double-blind, sham-controlled design was employed to compare balance training with active or sham tDCS. Participants underwent baseline assessments, followed by a six-week intervention period. The intervention protocol consisted of 2 mA, 20 min of anodal tDCS over the left primary motor cortex, three times weekly. Post-intervention assessments were conducted a few days after the intervention and follow-up at 4 weeks. Results: Following 18 sessions of anodal tDCS combined with balance exercise training, no significant group differences were observed for the Time Up and Go, One-Leg Standing, lower-limb strength, or the 6 min walk test (6MWT), although both the intervention and control groups demonstrated significant improvements over time. A significant group × time interaction was found only for the 6MWT, with participants in the intervention group exhibiting greater improvements in the 6MWT compared to controls. Conclusions: Anodal tDCS combined with balance exercise training selectively enhanced physical endurance but did not confer additional benefits for balance, gait, or leg strength in healthy older adults. These findings suggest that tDCS may serve as a promising adjunct to exercise for improving endurance-related outcomes in aging populations. Control of various variables for tDCS and exercise is necessary. Full article

Objectives: Transcranial alternating current stimulation (tACS) can enhance primary motor cortex (M1) excitability and improve motor skill when delivered unilaterally to the dominant hemisphere. However, the impact of tACS on contralateral M1 excitability both during and after application has not been studied. The purpose of this study was to examine the effects of tACS delivered to the dominant left M1 on the excitability of the unstimulated contralateral non-dominant right M1. Methods: This study implemented a double-blind, randomized, SHAM-controlled, within-subjects, crossover experimental design. Eighteen young adults completed a tACS condition and a SHAM condition on two different days in counterbalanced order with a week washout period between days. Transcranial magnetic stimulation (TMS) was utilized to assess excitability of the contralateral right M1 while tACS was delivered to the left M1. TMS was administered in five test blocks (termed Pre, D5, D10, D15, and Post) relative to a 20 min application of tACS (70 Hz, 1 mA current strength). The Pre and Post TMS test blocks were conducted before and immediately after tACS was applied to the left M1, whereas the TMS test blocks performed during tACS were completed at time points starting at the 5, 10, and 15 min marks of the 20 min stimulation period. The primary dependent variable was the 1 mV motor evoked potential (MEP) amplitude. MEP data were analyzed with a 2 condition (tACS, SHAM) × 5 test (Pre, D5, D10, D15, Post) within-subjects ANOVA. Results: The main effect for condition (p = 0.704) and condition × test interaction (p = 0.349) were both non-statistically significant. There was a significant main effect for test (p = 0.003); however, post hoc analysis indicated that none of the pairwise comparisons were statistically significant. Conclusions: Overall, the findings indicate that tACS applied to the left M1 does not significantly modulate contralateral right M1 excitability during or immediately after stimulation, at least when utilizing the present tACS parameters. Full article

Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median nerve with (2) transcranial magnetic stimulation over the primary motor cortex (M1) at different inter-stimulus intervals (25 ms; PAS-25, or 10 ms; PAS-10), corticospinal excitability can be increased (PAS-25, mimicking long-term potentiation (LTP)) or decreased (PAS-10, mimicking long-term depression (LTD)). However, variations in the number of pairings and inter-pair intervals lack consensus. The aim of the study was to evaluate four different PAS paradigms, i.e., PAS-10 and PAS-25 with both 180 versus 225 pairings each, to establish the most reliable PAS protocols for LTP- and LTD-like cortical changes. Methods: In a randomized, double-blind, crossover study, 14 healthy participants underwent PAS-10 and PAS-25 with 180 and 225 pairings. Excitability was assessed by quantifying the EMG response amplitude of a hand muscle to a single stimulus. Results: PAS-25 with 225 pairings produced a robust enhancement of corticospinal excitability, while PAS-25 with 180 pairings was less effective. Surprisingly, PAS-10 with both 180 and 225 pairings also increased excitability. Conclusions: While all four PAS paradigms enhanced M1 excitability, PAS-25 with 225 pairings induced the strongest group-level effects and was most time-efficient. Significant individual variability of PAS responses suggests that optimizing PAS parameters, including pairing number and interstimulus intervals, may be necessary for personalized approaches. Full article

Background/Objectives: Cerebellum might be one of the targets of repetitive transcranial magnetic stimulation (rTMS) for motor recovery in stroke patients. The aim of this study was to investigate the enhancing effects of rTMS over the cerebellum on inhibitory rTMS for motor recovery in patients with subacute ischemic stroke. Methods: Twenty-three patients with subacute ischemic stroke were recruited into this single-blind randomized, controlled study with a blinded observer. The Cr-Cbll group received Cr-Cbll rTMS consisting of continuous theta burst stimulation over the contralesional primary motor cortex (M1), a shoulder mobilization exercise, and high-frequency rTMS over the contralesional cerebellum. The Cr-sham group received sham rTMS over the cerebellum instead of high-frequency rTMS. All participants received ten daily sessions for 2 weeks. The Fugl-Meyer Assessment (FMA) was measured before, immediately after, and 2 months after the intervention. Results: A total of 20 participants (10 in the Cr-Cbll group and 10 in the Cr-sham group) who completed the two-week intervention were included in the intention-to-treat analysis. There was no significant difference in general and clinical characteristics between the two groups at baseline. Total and upper extremity scores of FMA showed a significant interaction between time and group (p < 0.05). Each improvement of upper extremity score of FMA immediately and 2 months after the intervention was significantly higher in the Cr-Cbll group than in the Cr-sham group (p < 0.05). Conclusions: These results demonstrated that rTMS over the cerebellum could have additional effects on inhibitory rTMS over contralesional M1 for improving upper extremity motor function in patients with subacute ischemic stroke. Full article

Early neurological deterioration is associated with poor functional outcomes in stroke patients, but the underlying mechanisms remain unclear. This study aims to understand the progression of stroke-related brain damage using a rhesus monkey model with ischemic occlusion. Multiparameter MRI was used to monitor the progressive evolution of the brain lesion following stroke. Resting-state functional MRI, dynamic susceptibility contrast perfusion MRI, diffusion tensor imaging, and T1- and T2-weighted scans were acquired prior to surgery and at 4–6 h, 48 h, and 96 h following the stroke. The results revealed a sudden increase in infarction volume after the hyper-acute phase but before 48 h on diffusion-weighted imaging (DWI), with a slight extension by 96 h. Lower relative cerebral blood flow (CBF) and time to maximum (Tmax) prior to the stroke, along with a progressive decrease post-stroke, were observed when compared to other stroke monkeys in the same cohort. Functional connectivity (FC) in the ipsilesional secondary somatosensory cortex (S2) and primary motor cortex (M1) exhibited an immediate decline on Day 0 compared to baseline and followed by a slight increase on Day 2 and a further decrease on Day 4. These findings provide valuable insights into infarction progression, emphasizing the critical role of collateral circulation and its impact on early neurological deterioration during acute stroke. Full article

Background/Objectives. Mirror properties of the action observation network (AON) can be modulated through Hebbian-like associative plasticity using paired associative stimulation (PAS). We recently introduced a visuomotor protocol (mirror–PAS, m-PAS) that pairs transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) with visual stimuli of ipsilateral (to TMS) movements, leading to atypical corticospinal excitability (CSE) facilitation (i.e., motor resonance) during PAS-conditioned action observation. While m-PAS aftereffects are robust, little is known about markers of associative plasticity during its administration and their predictive value for subsequent motor resonance rewriting. The present study aims to fill this gap by investigating CSE modulations during m-PAS and their relationship with the protocol’s aftereffects. Methods. We analyzed CSE dynamics in 81 healthy participants undergoing the m-PAS before and after passively observing left- or right-hand index finger movements. Here, typical and PAS-conditioned motor resonance was assessed with TMS over the right M1. We examined CSE changes during the m-PAS and used linear regression models to explore their relationship with motor resonance modulations. Results. m-PAS transiently reshaped both typical and PAS-induced motor resonance. Importantly, we found a gradual increase in CSE during m-PAS, which predicted the loss of typical motor resonance but not the emergence of atypical responses after the protocol’s administration. Conclusions. Our results suggest that the motor resonance reshaping induced by the m-PAS is not entirely predictable by CSE online modulations. Likely, this rewriting is the product of a large-scale reorganization of the AON rather than a phenomenon restricted to the PAS-stimulated motor cortex. This study underlines that monitoring CSE during non-invasive brain stimulation protocols could provide valuable insight into some but not all plastic outcomes. Full article

A substantial body of research suggests that early-life stress (ELS) is associated with neuropathology in adulthood. Maternal deprivation (MD) is a commonly utilised model in mice for the study of specific neurological diseases. The appropriate growth of dendrites is essential for the optimal functioning of the nervous system. However, the impact of ELS on interneuron dendritic morphology remains unclear. To ascertain whether ELS induces alterations in the morphology of GABAergic inhibitory interneurons in layers II/III of the medial entorhinal cortex (mEC), the somatosensory cortex (SSC), the motor cortex (MC), and the CA1 region of the hippocampus (Hp), 9-day-old male GAD-67-EGFP transgenic mice were subjected to a 24 h MD. At postnatal day 60 (P60), the animals were sacrificed, and their brains were subjected to morphological analyses. The results indicated that MD affected the dendritic morphology of GABAergic interneurons. The mean dendritic length and mean dendritic segments of the examined cortical areas, except for the MC, were significantly decreased, whereas the number of primary dendrites was unaffected. Furthermore, the density of GAD67-EGFP-positive interneurons was decreased in the mEC and Hp, but not in the somatosensory and MC. The induction of ELS through MD in a developmental time window when significant morphological changes occur rendered the developing cells particularly susceptible to stress, resulting in a significant reduction in the number of surviving interneurons at the adult stage. Full article

Background/Objectives: Beneficial effects of neurosteroid dehydroepiandrosterone sulphate (DHEAS) on cognition, emotions and behavior have been previously reported, suggesting its potential in the prevention and treatment of various neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease (AD). This study aimed to investigate the potential neuroprotective actions of DHEAS against Aβ toxicity in both cellular and animal models of AD. Methods: After optimizing the AD model in vitro, we investigated the DHEAS effects on the viability and death of primary mouse neurons exposed to toxic Aβ₄₂ oligomers for 24 h. In order to extend our research to an in vivo study, we further tested the acute effects of intraperitoneal DHEAS administration on the Aβ plaque density in different brain regions of 3xTg-AD mice, an animal model of AD. Results: In cell culture, DHEAS hampered the decrease in the neuronal viability caused by toxic Aβ oligomers, primarily by influencing mitochondrial function and apoptosis. DHEAS also counteracted the increase in the mRNA expression of selected genes (PI3K, Akt, Bcl2, Bax), induced in neuronal culture by treatment with Aβ₄₂ oligomers. Obtained data suggested the involvement of mitochondria, caspases 3 and 7, as well as the PI3K/Akt and Bcl2 signaling network in the antiapoptotic properties of DHEAS in neurons. Forty-eight hours after DHEAS treatment, a significantly lower number of Aβ plaques was observed in the motor cortex but not in other brain areas of 3xTg-AD mice. Conclusions: Results indicated potential neuroprotective effects of DHEAS against Aβ toxicity and accumulation, suggesting that DHEAS supplementation should be further studied as a novel option for AD prevention and/or treatment. Full article

Background/Objectives: Unilateral hand movements alter the excitability of the ipsilateral primary motor cortex (ipsi-M1) and contralateral spinal motoneurons. Although this excitability increases during complex, high muscle-activity movements, few studies have examined the excitability of ipsi-M1 and contralateral spinal motoneurons during complex movements while accounting for muscle activity. This study investigated the excitability of ipsi-M1 and contralateral spinal motoneurons during complex and simple movement tasks with comparable muscle activity between the two tasks. Methods: Nineteen healthy adult volunteers participated in this study. The ball rotation task was set as the complex movement task (BR condition), and the grasping task was set as the simple movement task (grasp condition), with peak muscle activity values comparable between the tasks. Motor-evoked potentials (MEPs) and F-waves were recorded from the abductor pollicis brevis muscle contralateral to the movement during task execution. The excitability parameters of ipsi-M1 and contralateral spinal motoneurons were calculated by dividing the MEP, F-wave persistence, and F/M amplitude values recorded in each condition by the corresponding values recorded at rest. These parameters were compared across the rest, BR, and grasp conditions. Results: All the excitability parameters of ipsi-M1 and contralateral spinal motoneurons increased during both the BR and grasp conditions compared with the rest condition but did not differ significantly between the BR and grasp conditions. Conclusions: The excitability of ipsi-M1 and contralateral spinal motoneurons was strongly influenced by the amount of muscle activity but not by the complexity of the movement. Full article

In this study, we investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left upper limb primary motor cortex (M1) on the offset analgesia (OA) phenomenon, a measure of endogenous pain modulation. In particular, we aim to determine whether rTMS influences OA differently in the forearm region, corresponding to the stimulated cortical area, compared to the trigeminal region. Twenty-two healthy volunteers underwent three experimental sessions: a baseline session without stimulation, an active rTMS session, and a sham rTMS session. Quantitative sensory testing (QST) paradigms, including warm and cold detection thresholds, heat pain threshold corresponding to a visual analogue scale (VAS) score of approximately 50–60 out of 100 (Pain_50–60), and constant and offset trials, were assessed in both the forearm and trigeminal regions. The results revealed that active rTMS significantly enhanced the OA phenomenon in the forearm during the late phase, while no significant effects were observed in the trigeminal region. These findings suggest that rTMS may modulate central pain mechanisms in a body region-specific manner, potentially linked to the somatotopic organization of M1. This study points to possible mechanisms of action of rTMS for pain relief, highlighting the importance of region-specific effects in chronic pain treatment. Further research is needed to investigate the underlying mechanisms and clinical applicability of rTMS in patients with chronic pain conditions, especially when OA is compromised. Full article

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation for treatment-resistant obsessive compulsive disorder (OCD). We aim to compare the treatment outcomes of a newly developed dual-site cathodal tDCS method over the orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA) and two previously reported montages (cerebellum-OFC and pre-SMA) in patients with treatment-resistant OCD. Methods: Eighteen OCD patients were randomly assigned to receive twice-daily 2 mA/20 min sessions for 10 consecutive weekdays, with the active cathode placed on the cerebellum-OFC, bilateral pre-SMA, or OFC-pre-SMA tDCS. The primary outcome was the change in the Yale–Brown Obsessive Compulsive Scale (Y-BOCS). The resting electroencephalogram (EEG) was recorded to obtain the default mode network (DMN) via low-resolution electromagnetic tomography. Each patient received one-week and one-month follow-ups after two weeks of stimulation. Results: At the end of the stimulation, the Y-BOCS scores in the cerebellum-OFC, pre-SMA, and OFC-pre-SMA tDCS groups (n = 6 in each group) were decreased by 14.15 ± 13.31, 7.4 ± 9.59, and 20.75 ± 8.70%, respectively, but no significant differences were found among the groups. In the OFC-pre-SMA tDCS group, OC symptoms significantly decreased by a mean of −20.75% immediately after the 20th tDCS session, and the improvement remained at 1 week and 1 month after tDCS. EEG source functional connectivity analyses revealed increased functional connectivity within the frontal network after OFC-pre-SMA tDCS, whereas decreased functional connectivity within the DMN was observed after cerebellum-OFC tDCS. Conclusions: Dual-site cathodal tDCS over the OFC and pre-SMA might be considered a potential montage to treat patients with treatment-resistant OCD. Future studies using randomized sham-controlled designs are needed. Full article

Background/Objectives: This study investigates the relationship between movement-related beta synchrony and primary motor cortex (M1) excitability, focusing on the time-dependent inhibition of movement. Voluntary movement induces beta frequency (13–30 Hz) event-related desynchronisation (B-ERD) in M1, followed by post-movement beta rebound (PMBR). Although PMBR is linked to cortical inhibition, its temporal relationship with motor cortical excitability is unclear. This study aims to determine whether PMBR acts as a marker for post-movement inhibition by assessing motor-evoked potentials (MEPs) during distinct phases of the beta synchrony profile. Methods: Twenty-five right-handed participants (mean age: 24 years) were recruited. EMG data were recorded from the first dorsal interosseous muscle, and TMS was applied to the M1 motor hotspot to evoke MEPs. A reaction time task was used to elicit beta oscillations, with TMS delivered at participant-specific time points based on EEG-derived beta power envelopes. MEP amplitudes were compared across four phases: B-ERD, early PMBR, peak PMBR, and late PMBR. Results: Our findings demonstrate that MEP amplitude significantly increased during B-ERD compared to rest, indicating heightened cortical excitability. In contrast, MEPs recorded during peak PMBR were significantly reduced, suggesting cortical inhibition. While all three PMBR phases exhibited reduced cortical excitability, a trend toward amplitude-dependent inhibition was observed. Conclusions: This study confirms that PMBR is linked to reduced cortical excitability, validating its role as a marker of motor cortical inhibition. These results enhance the understanding of beta oscillations in motor control and suggest that further research on altered PMBR could be crucial for understanding neurological and psychiatric disorders. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD’s pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between the motor symptoms of PD and transient changes in brain oscillations before and after motor tasks in different brain regions remain unclear. This study aimed to investigate neural oscillations in both healthy and PD model mice using local field potential (LFP) recordings from multiple brain regions during rest and locomotion. The histological evaluation confirmed the significant dopaminergic neuron loss in the injection side in 6-OHDA lesioned mice. Behavioral tests showed motor deficits in these mice, including impaired coordination and increased forelimb asymmetry. The LFP analysis revealed increased delta, theta, alpha, beta, and gamma band activity in 6-OHDA lesioned mice during movement, with significant increases in multiple brain regions, including the primary motor cortex (M1), caudate–putamen (CPu), subthalamic nucleus (STN), substantia nigra pars compacta (SNc), and pedunculopontine nucleus (PPN). Taken together, these results show that the motor symptoms of PD are accompanied by significant transient increases in brain oscillations, especially in the gamma band. This study provides potential biomarkers for early diagnosis and therapeutic evaluation by elucidating the relationship between specific neural oscillations and motor deficits in PD. Full article