Search Results (605)

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background: There are only a few available options for early rehabilitation of severely impaired individuals who must remain bedbound, as most exercise paradigms focus on out-of-bed exercises. To enable these individuals to exercise, we developed a novel hybrid rehabilitation system combining a brain–computer interface (BCI), functional electrical stimulation (FES), and a robotic device. Methods: The BCI assessed the presence of a movement-related cortical potential (MRCP) and triggered the administration of FES to produce movement of the lower limb. The exercise trajectory was supported by the robotic device. To demonstrate the system, an experiment was conducted in an out-of-lab setting by ten able-bodied participants. During exercise, the performance of the BCI was assessed, and the participants evaluated the system using the NASA Task Load Index, Intrinsic Motivation Inventory, and by answering a few subjective questions. Results: The BCI reached a true positive rate of 62.6 ± 9.2% and, on average, predicted the movement initiation 595 ± 129 ms prior to the MRCP peak negativity. All questionnaires showed favorable outcomes for the use of the system. Conclusions: The developed system was usable by all participants, but its clinical feasibility is uncertain due to the total time required for setting up the system. Full article

Sensory dysregulation represents a core challenge in autism spectrum disorder (ASD), affecting perception, behavior, and adaptive functioning. The brain’s ability to reorganize, known as neuroplasticity, serves as the basic principle for therapeutic interventions targeting these deficits. Neuroanatomical mechanisms include altered connectivity in the sensory and visual cortices, as well as in the limbic system and amygdala, while imbalances of neurotransmitters, in particular glutamate and gamma-aminobutyric acid (GABA), contribute to atypical sensory processing. Traditional therapies used in sensory integration are based on the principles of neuroplasticity. Increasingly, new treatments use this knowledge, and modern therapies such as neurofeedback, transcranial stimulation, and immersive virtual environments are promising in modulating neuronal circuits. However, further research is needed to optimize interventions and confirm long-term effectiveness. This review discusses the role of neuroplasticity in the etiopathogenesis of sensory integration deficits in autism spectrum disorder. The neuroanatomical and neurotransmitter basis of impaired perception of sensory stimuli is considered, and traditional and recent therapies for sensory integration are discussed. Full article

Parkinson’s disease (PD) is a progressive neurological disorder with motor and non-motor symptoms that are inadequately addressed by current pharmacological and surgical therapies. Brain–computer interfaces (BCIs), particularly those based on electroencephalography (eBCIs), provide a promising, non-invasive approach to personalized neurorehabilitation. This narrative review explores the clinical potential of BCIs in PD, discussing signal acquisition, processing, and control paradigms. eBCIs are well-suited for PD due to their portability, safety, and real-time feedback capabilities. Emerging neurophysiological biomarkers—such as beta-band synchrony, phase–amplitude coupling, and altered alpha-band activity—may support adaptive therapies, including adaptive deep brain stimulation (aDBS), as well as motor and cognitive interventions. BCIs may also aid in diagnosis and personalized treatment by detecting these cortical and subcortical patterns associated with motor and cognitive dysfunction in PD. A structured search identified 11 studies involving 64 patients with PD who used BCIs for aDBS, neurofeedback, and cognitive rehabilitation, showing improvements in motor function, cognition, and engagement. Clinical translation requires attention to electrode design and user-centered interfaces. Ethical issues, including data privacy and equitable access, remain critical challenges. As wearable technologies and artificial intelligence evolve, BCIs could shift PD care from intermittent interventions to continuous, brain-responsive therapy, potentially improving patients’ quality of life and autonomy. This review highlights BCIs as a transformative tool in PD management, although more robust clinical evidence is needed. Full article

Chronic neck pain is a multifactorial condition involving physical, psychological, and neurological dimensions. This case report describes the clinical course of a 25-year-old female with chronic neck pain and recurrent headaches who underwent a 6-week integrative intervention consisting of manual therapy and pain neuroscience-based sensorimotor retraining, administered three times per week. Outcome measures included the Headache Impact Test-6 (HIT-6), Neck Pain and Disability Scale (NPDS), Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ), pressure pain threshold (PPT), cervical range of motion (CROM), and functional near-infrared spectroscopy (fNIRS) to assess brain activity. Following the intervention, the patient demonstrated marked reductions in pain and psychological distress: HIT-6 decreased from 63 to 24 (61.9%), NPDS from 31 to 4 (87.1%), FABQ from 24 to 0 (100%), and PCS from 19 to 2 (89.5%). Improvements in PPT and CROM were also observed. fNIRS revealed decreased dorsolateral prefrontal cortex (DLPFC) activation during pain stimulation and movement tasks, suggesting a possible reduction in central sensitization burden. These findings illustrate that an integrative approach targeting biopsychosocial pain mechanisms may be beneficial in managing chronic neck pain, improving function, and modulating cortical responses. This report provides preliminary evidence in support of the clinical relevance of combining manual therapy with neurocognitive retraining in similar patients. Full article

Background/Objectives: Neck pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, affecting the cervical region. It represents one of the leading causes of disability, with a prevalence of 30%. Transcranial direct current stimulation (tDCS) is a non-invasive electrotherapy technique that enables direct modulation of cortical excitability. It involves the application of a low-intensity electrical current to the scalp, targeting the central nervous system. The aim of this study was to analyze the effects of tDCS on functionality, pain, mobility, and pressure pain threshold in patients with chronic nonspecific neck pain. Methods: Thirty participants (18–60 years) were selected to receive ten treatment sessions over a four-week period using tDCS (CG = 15) or transcutaneous electrical nerve stimulation (TENS) (CG = 15), with the following various related variables evaluated: functionality (Neck Disability Index), pain intensity (NPRS), cervical range of motion (ROM), and pressure pain threshold (PPT). Assessments were conducted at baseline, post-treatment, one month, and three months after the intervention. Results: The within-group analysis revealed statistically significant improvements for both groups at post-treatment, one-month follow-up, and three-month follow-up. Conclusions: The comparison between groups shows favorable changes in the tDCS group for PPT measurements. Full article

The balance between cortical excitation and inhibition (E/I balance) in the cerebral cortex is critical for cognitive processing and neuroplasticity. Modulation of this balance has been linked to a wide range of neuropsychiatric and neurodegenerative disorders. The human visual system has well-differentiated magnocellular (M) and parvocellular (P) pathways, which provide a useful model to study cortical excitability using non-invasive visual flicker stimulation. We present an Arduino-driven non-image forming system to deliver controlled flickering light stimuli at different frequencies and wavelengths. By triggering the critical flicker fusion (CFF) frequency, we attempt to modulate the M-pathway activity and attenuate P-pathway responses, in parallel with induced optical scattering. EEG recordings were used to monitor cortical excitability and oscillatory dynamics during visual stimulation. Visual stimulation in the CFF, combined with induced optical scattering, selectively enhanced magnocellular activity and suppressed parvocellular input. EEG analysis showed a modulation of cortical oscillations, especially in the high frequency beta and gamma range. Our results support the hypothesis that visual flicker in the CFF, in addition to spatial degradation, initiates detectable neuroplasticity and regulates cortical excitation and inhibition. These findings suggest new avenues for therapeutic manipulation through visual pathways in diseases such as Alzheimer’s disease, epilepsy, severe depression, and schizophrenia. Full article

Background and Objectives: Arthrogenic muscle inhibition (AMI) is a key neurophysiological barrier to effective rehabilitation in individuals with chronic ankle instability (CAI). The primary objective of this narrative review is to explore the role of arthrogenic muscle inhibition (AMI) in chronic ankle instability (CAI) and to critically appraise neurophysiological and rehabilitative strategies targeting its resolution. Although peripheral strengthening remains a cornerstone of treatment, the roles of spinal and cortical modulation are increasingly recognised. Materials and Methods: A narrative review was conducted to examine recent clinical trials targeting AMI in CAI populations. A structured search of MEDLINE, Web of Science, Scopus, Cochrane Central, and PEDro was performed. Five studies were included, encompassing peripheral, spinal, and cortical interventions. The outcomes were grouped and analysed according to neurophysiological and functional domains. Results: Manual therapy combined with exercise improved pain, strength, and functional mobility. Fibular reposition taping transiently enhanced spinal reflex excitability, while transcranial direct current stimulation (tDCS) over the primary motor cortex significantly modulated corticospinal excitability and voluntary muscle activation. Improvements in subjective stability, dynamic balance, and neuromuscular responsiveness were observed in the majority of the five included studies, although methodological heterogeneity and short-term follow-ups limit generalisability. Conclusions: Multimodal interventions targeting different levels of the neuromotor system appear to be more effective than isolated approaches. Integrating manual therapy, sensorimotor training, and neuromodulation may optimise outcomes in CAI rehabilitation. Future trials should focus on standardised outcome measures and long-term efficacy. Full article

Transcranial direct current stimulation (tDCS) modulates cortical excitability, thus inducing improvements in motor learning of simple tasks. In this study, we aimed to evaluate the effect of different tDCS conditions—anodal stimulation over the motor cortex (M1), anodal and cathodal stimulation over the prefrontal cortex (PFC), and sham—on the online and offline learning of a complex accuracy task (golf-putting) in novice golfers. Methods: A total of 40 young, healthy subjects (24 men, 16 women) without previous golf experience were randomly distributed in four groups receiving sham, anodal M1, anodal PFC or cathodal PFC tDCS. All subjects participated in two consecutive sessions. In the first session, they performed 15 blocks of 10 golf-putting along with tDCS stimulation. After 24 h, they performed the same task without tDCS. Results: Repeated measures ANOVA revealed a significant improvement in performance during the two consecutive golf-putting sessions regardless of the site and the stimulation conditions. Conclusion: Our findings suggest that tDCS over M1 or PFC does not confer additional benefits in the acquisition of complex, full-body motor skills such as golf-putting. Full article

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a transformative tool for probing cortical dynamics with millisecond precision. This review examines the state-dependent nature of TMS-EEG, a critical yet underexplored dimension influencing measurement reliability and clinical applicability. By integrating TMS’s neuromodulatory capacity with EEG’s temporal resolution, this synergy enables real-time analysis of brain network dynamics under varying neural states. We delineate foundational mechanisms of TMS-evoked potentials (TEPs), discuss challenges posed by temporal and inter-individual variability, and evaluate advanced paradigms such as closed-loop and task-embedded TMS-EEG. The former leverages real-time EEG feedback to synchronize stimulation with oscillatory phases, while the latter aligns TMS pulses with task-specific cognitive phases to map transient network activations. Current limitations—including hardware constraints, signal artifacts, and inconsistent preprocessing pipelines—are critically analyzed. Future directions emphasize adaptive algorithms for neural state prediction, phase-specific stimulation protocols, and standardized methodologies to enhance reproducibility. By bridging mechanistic insights with personalized neuromodulation strategies, state-dependent TMS-EEG holds promise for advancing both basic neuroscience and precision medicine, particularly in psychiatric and neurological disorders characterized by dynamic neural dysregulation. Full article

Freezing of gait (FOG) is a disabling symptom associated with Parkinson’s disease (PD). Its understanding and effective treatment is compromised due to the difficulty in reliably triggering FOG in clinical and laboratory environments. The Cleveland Clinic-Virtual Home Environment (CC-VHE) platform was developed to address the challenges of eliciting FOG by combining an omnidirectional treadmill with immersive virtual reality (VR) environments to induce FOG under physical, emotional, and cognitive triggers. Recent developments in deep brain stimulation devices that sense neural signals from the subthalamic nucleus in real time offer the potential to understand the underlying neural mechanism(s) of FOG. This manuscript presents the coupling of the CC-VHE technology, VR paradigms, and the experimental and analytical methods for recording and analyzing synchronous cortical, subcortical, and kinematic data as an approach to begin to understand the nuanced neural pathology associated with FOG. To evaluate the utility and feasibility of coupling VR and neural sensing technology, initial data from one participant are included. Full article

Exploring the neurogenic potential of extraneural stem cells under the actions of proneurogenic biomolecules may enhance the success of autologous cell therapy for neurodegenerative diseases such as Parkinson’s. Neural stem and progenitor cells (NSPCs) from extraneural tissues have emerged as potential sources of functional dopaminergic (DA) neurons. Background/Objectives: This study aimed to generate DA neurons from ovarian cortical cells (OCC)-derived NSPCs to elucidate whether follicle-stimulating hormone (FSH) can enhance this process and to evaluate the electrophysiological functionality of differentiated neural cells using the patch-clamp technique. Methods: OCC-NSPCs were differentiated towards the DA pathway during the neurosphere (NS) assay after two culture periods for cell expansion (CEP-1, CEP-2) with one of these media: M1 (positive control with epidermal growth factor, EGF, and fibroblast growth factor2, FGF2), M2 (control), and M3 (M2 with FSH, 50 ng/mL). Image analysis, morphometric evaluation, cell proliferation assays, and gene expression analysis of NSPC-specific transcripts were performed. After CEP-2, NS cells were cultured for 30 days in a serum-free medium containing Sonic-Hedgehog, FGF2, FGF8, and brain-derived neurotrophic factor (BDNF) for differentiation. At the end of culture, expression, and immunolocalization of GFAP, Olig2, NeuN, and tyrosine hydroxylase (TH) were analyzed in cells, along with patch-clamp recordings in differentiated neurons. Results: Cell proliferation and NS development were larger in OCC-NSPCs from groups M1 and M3 than in M2. Expression of NSPC-related transcripts was higher in M2; however, M1 and M3 cultures showed greater expression of differentiation markers NeuN, GFAP, Olig2, and TH. NeuN, GFAP, and TH were immunolocalized in differentiated cells and NS that were generated during differentiation. TH was localized in neural precursor cells, some neurons, core cells of small-, medium-, and large-sized NS, and in cells close to the outer cell layer of large NS, with greatest immunolocalization percentages in NS primed with FSH during CEP-1/2 (M3). Electrophysiological recordings revealed a major incidence of plateau potentials and a significant proportion of complete action potentials, reflecting successful functional neuronal differentiation. Conclusions: DA precursors and functional neurons can be successfully obtained after OCC-NSPCs-directed differentiation. FSH priming during the expansion period enhances the neurogenic potential of these cells towards the DA pathway. Future research will explore the eventual therapeutic use of these findings for neurodegenerative diseases. Full article

The effects of Transcranial Magnetic Stimulation (TMS) depend on stimulation parameters such as intensity, location, frequency, and duration. In clinical practice, these parameters are often adapted from studies carried out in healthy individuals. However, in this narrative review, we indicate that the impact of TMS is also highly state-dependent, meaning it is influenced by the excitability of the targeted brain region at the time of stimulation. This state-dependency complicates the translation of findings from healthy individuals to clinical populations, as neurological disorders often alter brain states, limiting the applicability of standard stimulation protocols. To address this challenge, stimulation parameters must be chosen within a framework that accounts for the interaction between external stimulation and the brain’s internal state. Such an approach enhances the specificity of interventions, allowing for targeted modulation of neural populations by manipulating brain states prior to stimulation. State-dependent TMS has shown promise in conditions like cortical blindness and amblyopia, where tailored approaches based on the brain state associated with the condition have facilitated more precise and effective treatments. We advocate that integrating state-dependent knowledge tailored to the specifics of visual disorders alongside judicious selection of stimulation parameters holds the potential to establish a comprehensive paradigm for future investigations. Full article

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills. Full article

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer’s disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson’s disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms—such as depression, cognitive decline, and the freezing of gait—through theoretical modulation of basal ganglia–cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks. Full article