Search Results (27)

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder marked by motor and non-motor symptoms, including cognitive decline, mood disturbances, and sensory deficits. While dopaminergic treatments remain the gold standard, they present long-term side effects and limited impact on non-motor symptoms. Transcranial Pulse Stimulation (TPS) has emerged as a promising adjunct therapy in neurological and psychiatric conditions, but its effects in PD remain underexplored. This open-label, single-arm trial protocol involves 14 PD participants and outlines a personalized 12-session treatment approach combined with a homogeneously distributed TPS intervention among patients with PD. The approach addresses the subject’s most prominent symptoms, as identified through validated clinical assessments, encompassing domains related to both motor and non-motor symptoms. Over 2.5 months, besides the intervention sessions, the 14 participants will undergo an MRI brain scan, a baseline assessment, a post-treatment assessment, and a 1-month follow-up assessment. The study aims to determine whether personalized TPS is a feasible and safe intervention and whether it improves PD symptoms across multiple functional domains. This study represents the first structured attempt to evaluate a multimodal, personalized TPS intervention in patients with PD. It addresses gaps in current treatment approaches and may support the development of future strategies for integrated, symptom-targeted neuromodulation. 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

Background: The impact of exogenous explicit knowledge on early motor learning is highly variable and may be influenced by excitability within the procedural sensorimotor network. Recent transcranial magnetic stimulation (TMS) studies suggest that variability in interneuron recruitment by anterior–posterior (AP) currents is linked to differences in functional connectivity between premotor and motor regions. Objectives: This study used controllable pulse parameter TMS (cTMS) to assess how AP-sensitive interneuron excitability interacts with explicit knowledge to influence motor learning. Methods: Seventy-two participants were grouped as AP-positive (n = 36) and AP-negative groups (n = 36) based on whether an AP threshold could be obtained before reaching maximal stimulator output. A narrow (30 µs) stimulus was employed to target the longest latency corticospinal inputs selectively. Participants then practiced a continuous visuomotor tracking task and completed a delayed retention test. Half of each group received explicit knowledge of a repeated sequence embedded between random sequences. Random sequence tracking performance assessed general sensorimotor efficiency; repeated sequence performance assessed sequence-specific learning. Results: Both AP₃₀-positive participants, with and without explicit knowledge, and the AP₃₀-negative without explicit knowledge demonstrated similar improvements in sensorimotor efficiency driven by offline consolidation. However, AP₃₀-negative participants given explicit instruction exhibited significantly reduced improvement in sensorimotor efficiency, primarily due to impaired offline consolidation. Conclusions: These findings suggest that individuals with low excitability in long-latency AP-sensitive inputs may be more vulnerable to interference from explicit instruction. The current results highlight the importance of accounting for individual differences in interneuron excitability when developing instructional strategies for motor learning. Full article

Alzheimer’s disease (AD), the most prevalent form of dementia, is marked by progressive cognitive decline, affecting memory, language, orientation, and behavior. Pathological hallmarks include extracellular amyloid plaques and intracellular tau tangles, which disrupt synaptic function and connectivity. Neural oscillations, the rhythmic synchronization of neuronal activity across frequency bands, are integral to cognitive processes but become dysregulated in AD, contributing to network dysfunction and memory impairments. Targeting these oscillations has emerged as a promising therapeutic strategy. Preclinical studies have demonstrated that specific frequency modulations can restore oscillatory balance, improve synaptic plasticity, and reduce amyloid and tau pathology. In animal models, interventions, such as gamma entrainment using sensory stimulation and transcranial alternating current stimulation (tACS), have shown efficacy in enhancing memory function and modulating neuroinflammatory responses. Clinical trials have reported promising cognitive improvements with repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), particularly when targeting key hubs in memory-related networks, such as the default mode network (DMN) and frontal–parietal network. Moreover, gamma-tACS has been linked to increased cholinergic activity and enhanced network connectivity, which are correlated with improved cognitive outcomes in AD patients. Despite these advancements, challenges remain in optimizing stimulation parameters, individualizing treatment protocols, and understanding long-term effects. Emerging approaches, including transcranial pulse stimulation (TPS) and closed-loop adaptive neuromodulation, hold promise for refining therapeutic strategies. Integrating neuromodulation with pharmacological and lifestyle interventions may maximize cognitive benefits. Continued interdisciplinary efforts are essential to refine these approaches and translate them into clinical practice, advancing the potential for neural oscillation-based therapies in AD. Full article

Background: Both transcranial direct current stimulation (tDCS) and acupuncture are promising methods for managing chronic low back pain (cLBP), however, their underlying mechanisms remain unclear. Methods: To explore the neural mechanisms of tDCS and acupuncture on cLBP, we examined how real and sham tDCS applied to the bilateral motor cortex (M1), combined with real or sham acupuncture, influenced cerebral blood flow (CBF) using pulsed continuous arterial spin labeling (pCASL) imaging. tDCS was administered over six sessions, combined with real or sham acupuncture, over one month. Results: Following real tDCS, we observed increased CBF in the bilateral occipital cortex, precuneus, left hippocampus, and parahippocampal gyrus/posterior cingulate cortex. After sham tDCS, CBF decreased in regions including the bilateral superior parietal lobule, precuneus, bilateral precentral and postcentral gyri, and left angular gyrus. Real acupuncture led to reduced CBF in the bilateral occipital cortex and hippocampus, and left posterior cingulate gyrus, and increased CBF in the right postcentral gyrus, superior parietal lobule, and frontal areas. Sham acupuncture was associated with decreased CBF in the bilateral hippocampus and anterior cingulate gyrus. Conclusions: These results suggest both shared and distinct patterns of CBF changes between real and sham tDCS, as well as between real and sham acupuncture, reflecting mode-dependent effects on brain networks involved in pain processing and modulation. Our findings highlight the different neural circuits implicated in the therapeutic mechanisms of tDCS and acupuncture in the management of cLBP. Full article

This study proposes a high-frequency Pulse Amplitude-Modulation Temporal-Interference (PAM-TI) current stimulation device, which utilizes two sets of Amplitude-modulated transcranial alternating current stimulation (AM-tACS): one AM frequency at f0 (where f0 = 2 kHz) (source 1) and the other AM frequency at f1 = f0 + $△$f (where f1 = 2.01 kHz) (source 2), to generate a $△$f (where $△$f = 10 Hz) envelope modulated at a fc (where fc = 100 kHz) high carrier frequency. The high carrier frequency reduces body impedance and conserves more stimulation power, allowing it to penetrate the skin and reach the subcutaneous region. The proposed PAM-TI technique elevates the two current sources to a 100 kHz carrier frequency. Instead of the challenges associated with generating high-frequency stimulation currents using an MCU and DAC, the proposed PAM-TI stimulation device achieves this by simply utilizing a pair of complementary pulse-width modulations (PWMs). The push–pull technique is employed to balance the charging currents between the anode and cathode, synchronizing the current timing of Source 1 and Source 2 under the fc modulation condition. To minimize signal attenuation, the PAM circuit is integrated directly into the electrode, ensuring the high-frequency signal is generated close to the body and preventing degradation from long wires. Additionally, a dry pin-type spring-loaded electrode is used to reduce interference caused by hair when placed on the head. The device’s validity and current directionality were verified using a scalp tissue-mimicking phantom composed of agar and saline. Full article

Obsessive–Compulsive Disorder (OCD) is a chronic psychiatric condition with a lifetime prevalence of 2–3%. It significantly burdens quality of life and is associated with substantial economic and disease burdens. Cognitive-behavioral therapy and high-dose selective serotonin reuptake inhibitors are considered the first-line treatments for OCD. Approximately two-thirds of patients with Obsessive–Compulsive Disorder (OCD) exhibit inadequate responses to current standard therapies, thus lacking adequate therapy, resulting in a loss of quality of life and huge economic burdens. Repetitive transcranial stimulation (rTMS) is a non-invasive, safe, and well-tolerated intervention that modulates prefrontal cortical circuits involved in OCD. A previous systematic review explored the therapeutic effects of rTMS applied to the dorsolateral prefrontal cortex (dlPFC) area in patients with treatment-resistant OCD. It showed that the application of high-frequency and low-frequency (LF) rTMS to the dlPFC region yielded controversial post-treatment Y-BOCS (Yale-Brown Obsessive–Compulsive Scale) findings due to factors such as small sample sizes, short-term study durations, and variations in rTMS protocols. Objectives: Thus, we propose a theoretical protocol based on previous findings to assess better the effect of LF rTMS for treatment-resistant OCD patients. Methods: We will recruit patients with moderate to severe OCD and limited response to previous treatments from in- and outpatient clinics. We will use fMRI for precious localization of the right dlPFC and application of 1 Hz stimulation of in total 2000 pulses with three times 40 s inter-train intervals 5 days a week, in 6 consecutive weeks. The primary outcome will be the mean reduction in Y-BOCS at the end of this study. Conclusions: This study highlights rTMS’s potential to reform OCD treatment, accentuate safety, accessibility, clinical integration, and future research foundations. Full article

This paper presents a high-frequency (HF) magnetic pulse generator designed for low-intensity transcranial magnetic stimulation (LI-TMS) applications. HF pulse stimulation can induce a strong electric field with minimal current and enhance the penetration depth of the electric field in human tissue. The HF magnetic pulse generator was designed and fabricated using a microcontroller unit, gate driver, full-bridge coil driver, and stimulation coil. Measurements with a full-bridge circuit supply voltage of 10 V demonstrated an electric field intensity of 6.8 V_pp/m at a frequency of 1 MHz with a power dissipation of 2.45 W. Achieving a similar electric field intensity at a frequency of 100 kHz required approximately ten times the coil current. Additionally, a quasi-resonant LC load was introduced by connecting a capacitor in series with the stimulation coil, which set the resonant frequency to approximately 10% higher than the frequency of 1 MHz. This approach reduced the coil impedance, achieving higher current with the same bias supply voltage. Experimental results showed an enhanced electric field intensity of 19.1 V_pp/m with a supply voltage of only 1.8 V and reduced power dissipation of 1.11 W. The proposed HF pulse train with quasi-resonant coil system is expected to enable a low-power LI-TMS system. Full article

Non-invasive transcranial electrical stimulation is a category of neuromodulation techniques used for various disorders. Although medically approved devices exist, the variety of consumer electrical stimulation devices is increasing. Because clinical trials and animal tests are costly and risky, using a brain phantom can provide preliminary experimental validation. However, existing brain phantoms are often costly or require excessive preparation time, precluding their use for rapid, real-time optimization of stimulation settings. A limitation of direct electric fields in a phantom is the lack of 3D spatial resolution. Using well-researched modalities such as transcranial direct current stimulation (tDCS) and newer modalities such as amplitude-modulated transcranial pulsed-current stimulation (am-tPCS), a range of materials was tested for use as electrical phantoms. Based on cost, preparation time, and efficiency, ground beef and agar gel with a 10% salt mix were selected. The measured values for the total dosages were 0.55 W-s for am-tPCS and 0.91 W-s for tDCS. Due to a low gain on the recording electrodes, the signal efficiency measured against the power delivered was 4.2% for tDCS and 3.1% for am-tPCS. Issues included electrodes shifting in the soft material and the low sensitivity of the recording electrodes. Despite these issues, the effective combination of the phantom and recording methodologies can enable low costs and the rapid testing, experimentation, and verification of consumer neuromodulation devices in three dimensions. Additionally, the efficiency factors (EFs) between the observed dosage and the delivered dosage could streamline the comparison of experimental configurations. As demonstrated by comparing two types of electrical neuromodulation devices across the 3D space of a phantom, EFs can be used in conjunction with a cost-effective, time-expedient phantom to rapidly iterate and optimize stimulation parameters. Full article

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly developing therapeutic modality for the safe and effective treatment of neuropsychiatric disorders. However, clinical rTMS driving systems and head coils are large, heavy, and expensive, so miniaturized, affordable rTMS devices may facilitate treatment access for patients at home, in underserved areas, in field and mobile hospitals, on ships and submarines, and in space. The central component of a portable rTMS system is a miniaturized, lightweight coil. Such a coil, when mated to lightweight driving circuits, must be able to induce B and E fields of sufficient intensity for medical use. This paper newly identifies and validates salient theoretical considerations specific to the dimensional scaling and miniaturization of coil geometries, particularly figure-8 coils, and delineates novel, key design criteria. In this context, the essential requirement of matching coil inductance with the characteristic resistance of the driver switches is highlighted. Computer simulations predicted E- and B-fields which were validated via benchtop experiments. Using a miniaturized coil with dimensions of 76 mm × 38 mm and weighing only 12.6 g, the peak E-field was 87 V/m at a distance of 1.5 cm. Practical considerations limited the maximum voltage and current to 350 V and 3.1 kA, respectively; nonetheless, this peak E-field value was well within the intensity range, 60–120 V/m, generally held to be therapeutically relevant. The presented parameters and results delineate coil and circuit guidelines for a future miniaturized, power-scalable rTMS system able to generate pulsed E-fields of sufficient amplitude for potential clinical use. Full article

Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses electromagnetic pulses for focal modulate ion of neuronal activity in brain cortical regions. When pulses are applied repeatedly (repetitive transcranial magnetic stimulation—rTMS), they are thought to induce long-lasting neuroplastic effects, proposed to be a therapeutic mechanism for rTMS, with efficacy and safety initially demonstrated for treatment-resistant depression (TRD). Since then, many rTMS treatment protocols emerged for other difficult to treat psychiatric conditions. Moreover, multiple clinical studies, including large multi-center trials and several meta-analyses, have confirmed its clinical efficacy in different neuropsychiatric disorders, resulting in evidence-based guidelines and recommendations. Currently, rTMS is cleared by multiple regulatory agencies for the treatment of TRD, depression with comorbid anxiety disorders, obsessive compulsive disorder, and substance use disorders, such as smoking cessation. Importantly, current research supports the potential future use of rTMS for other psychiatric syndromes, including the negative symptoms of schizophrenia and post-traumatic stress disorder. More precise knowledge of formal indications for rTMS therapeutic use in psychiatry is critical to enhance clinical decision making in this area. Full article

The non-invasive current stimulation protocol differs significantly between the brain and spinal cord, such that when comparing the two, there is a clear predominance of protocols using transcranial direct current stimulation (tDCS) for the brain and of protocols using pulsed stimulation for the spinal cord (psSC). These protocols differ in their effects on the central nervous system and in such important parameters as stimulation intensity. In most cases, tDCS has a fixed amplitude for all subjects/patients, while psSC is usually chosen on a case-by-case basis, according to the thresholds of muscle responses. In our opinion, it is possible to use the experience of identifying thresholds during psSC to adjust the dose of the direct current for transcranial and transspinal electrical stimulation, an approach that may provide more homogeneous tDCS data. Full article

Transcranial direct current stimulation (tDCS) is a promising non-invasive method to modulate brain excitability. The aim of this study was to better understand the cerebral blood flow (CBF) changes during and after repeated tDCS at the right dorsolateral prefrontal cortex (DLPFC) in healthy participants using pulsed continuous arterial spin labeling (pCASL). Elucidating CBF changes associated with repeated tDCS may shed light on the understanding of the mechanisms underlying the therapeutic effects of tDCS. tDCS was applied for three consecutive days for 20 min at 2 mA, and MRI scans were performed on day 1 and 3. During anodal tDCS, increased CBF was detected in the bilateral thalamus on day 1 and 3 (12% on day 1 and of 14% on day 3) and in the insula on day 1 (12%). After anodal tDCS on day 1, increased CBF was detected in the cerebellum and occipital lobe (11.8%), while both cathodal and sham tDCS were associated with increased CBF in the insula (11% and 10%, respectively). Moreover, anodal tDCS led to increased CBF in the lateral prefrontal cortex and midcingulate cortex in comparison to the sham. These findings suggest that tDCS can modulate the CBF and different tDCS modes may lead to different effects. Full article

Transcranial pulse stimulation (TPS) is a recent development in non-invasive brain stimulations (NIBS) that has been proven to be effective in terms of significantly improving Alzheimer patients’ cognition, memory, and execution functions. Nonetheless, there is, currently, no trial evaluating the efficacy of TPS on adults with major depression disorder (MDD) nationwide. In this single-blinded, randomized controlled trial, a 2-week TPS treatment comprising six 30 min TPS sessions were administered to participants. Participants were randomized into either the TPS group or the Waitlist Control (WC) group, stratified by gender and age according to a 1:1 ratio. Our primary outcome was evaluated by the Hamilton depression rating scale-17 (HDRS-17). We recruited 30 participants that were aged between 18 and 54 years, predominantly female (73%), and ethnic Chinese from 1 August to 31 October 2021. Moreover, there was a significant group x time interaction (F(1, 28) = 18.8, p < 0.001). Further, when compared with the WC group, there was a significant reduction in the depressive symptom severity in the TPS group (mean difference = −6.60, p = 0.02, and Cohen’s d = −0.93). The results showed a significant intervention effect; in addition, the effect was large and sustainable at the 3-month follow-up. In this trial, it was found that TPS is effective in reducing depressive symptoms among adults with MDD. Full article

Chronic pain is associated with abnormal cortical excitability and increased pain intensity. Research investigating the potential for transcranial direct current stimulation (tDCS) to modulate motor cortex excitability and reduce pain in individuals with chronic lower back pain (CLBP) yield mixed results. The present randomised, placebo-controlled study examined the impact of anodal-tDCS over left-dorsolateral prefrontal cortex (left-DLPFC) on motor cortex excitability and pain in those with CLBP. Nineteen participants with CLBP (Mage = 53.16 years, SDage = 14.80 years) received 20-min of sham or anodal tDCS, twice weekly, for 4 weeks. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed using paired-pulse Transcranial Magnetic Stimulation prior to and immediately following the tDCS intervention. Linear Mixed Models revealed no significant effect of tDCS group or time, on SICI or ICF. The interactions between tDCS group and time on SICI and ICF only approached significance. Bayesian analyses revealed the anodal-tDCS group demonstrated higher ICF and SICI following the intervention compared to the sham-tDCS group. The anodal-tDCS group also demonstrated a reduction in pain intensity and self-reported disability compared to the sham-tDCS group. These findings provide preliminary support for anodal-tDCS over left-DLPFC to modulate cortical excitability and reduce pain in CLBP. Full article