Transcranial Stimulation Research Articles

Feasibility of Neuromodulation for Treating Subjective Tinnitus: A Comparison of Transcutaneous Vagus Nerve Stimulation and Transcranial Random Noise Stimulation

Background and Objectives The efficacy of non-invasive neuromodulation techniques for treating tinnitus has been investigated with varying results. The purpose of current study was to evaluate the feasibility of two forms of neuromodulation, the transcutaneous vagus nerve stimulation (tVNS) and the transcranial random noise stimulation (tRNS), as treatments for chronic tinnitus.Subjects and Method A total of 24 tinnitus patients were enrolled in the study, with 11 receiving tVNS and 13 receiving tRNS. Four subjective questionnaires and electroencephalogram (EEG) tests were conducted to evaluate the effects of neuromodulation on cortical activity.Results Both tVNS and tRNS significantly reduced the intensity and distress of tinnitus, as well as Tinnitus Handicap Inventory scores 3 days after treatment. These effects persisted for 1 month with no significant differences between the two treatments. The EEG data revealed a notable decrease in the power of the beta and gamma bands primarily in the auditory cortex on the opposite side of stimulation for both tVNS and tRNS. The decrease in the power of the beta band was more widespread in the tRNS group than in the tVNS group, affecting the entire brain 3 days after treatment. Furthermore, this reduced activity continued for several electrodes up to 1 month after treatment. The correlation analysis indicated a significant relationship between decreased neural activity and reduction in tinnitus symptoms in both treatment groups.Conclusion This study provides evidence for both tVNS and tRNS to be promising treatment methods for patients suffering from tinnitus. However, tVNS and tRNS have different mechanisms of action in modulating neural activity and improving tinnitus-related outcomes.

Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K+-selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings.

Effect of Transcranial Direct-Current Stimulation and Task-Oriented Training on Electroencephalography- Based Motor Recovery Chronic Stroke: A Randomized Clinical Trial

Introduction: Upper limb motor disability, with a prevalence of approximately 77%, is the most common complication after stroke. Despite advancements in rehabilitation, many patients face persistent upper limb discrepancies. Adopting top-down and bottom-up interventions may enhance neuroplasticity and improve upper limb function. This study aims to determine the effect of motor cortical transcranial direct-current stimulation (tDCS) as a top-down approach combined with task-oriented training (TOT) as a bottom-up intervention on changes in electroencephalography (EEG) spectral power in chronic stroke patients. Materials and Methods: Thirty chronic hemiparetic stroke survivors were randomly assigned to receive real or sham stimulation targeting the primary motor cortex (C3/C4) at 2 mA for 20 minutes and TOT daily over 15 sessions. EEG was conducted before and after the intervention, with a 3-month follow-up and the relative powers of delta to gamma frequency bands were recorded during the movement task with each hand (healthy and involved). Results: Significant differences in the theta (P=0.000), alpha (P=0.004), beta (P=0.000) and gamma (P=0.003) relative powers were observed between groups at follow-up. Additionally, the Friedman test revealed a significant decrease in alpha and beta bands’ relative powers in the healthy hand of the control group at follow-up (P=0.001). The experimental group displayed increased alpha and beta powers and decreased theta without statistical significance. Conclusion: The increase in the relative power of low frequencies and the decrease in high frequencies in the sham group, which were more prominent than the increases in alpha and beta bands’ relative power and the decrease in theta in the experimental group, can indicate that the real-tDCS can prevent the recovery drop of relative powers. Due to the inconsistent effects of tDCS on the EEG power spectrum in stroke patients, conventional tDCS administration may require adjustments for optimal application to brain target points.

Effects of Transcranial Direct-Current Stimulation and Cognitive Training on Individuals with Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis

Introduction: We aimed to systematically evaluate the most recent evidence regarding the potential short-term and long-term synergistic effects of transcranial direct-current stimulation (tDCS) and cognitive training (CT) on the memory of individuals with mild cognitive impairment (MCI) or dementia and to explore the optimal treatment protocol. Materials and Methods: Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a comprehensive literature search on PubMed, Medline, CINAHL and EMBASE was conducted to identify eligible randomized controlled trials (RCTs) published up to December 2022. The identified studies were summarized and analyzed to examine the efficacy of the combined intervention. Results: Ten studies involving participants with MCI or dementia were included. Four RCTs with memory-related outcomes were analyzed. A small-to-medium effect size (ES) of 0.28 was found for the short-term effect (95% CI, 0.02%, 0.55%). However, the long-term effect was non-significant, with an ES of 0.17 (95% CI, -0.09%, 0.44%). Conclusion: The combined intervention appears to effectively mitigate cognitive decline in the short term only. Optimal treatment protocol remains inconclusive due to heterogeneity among studies. More robust evidence is required to determine whether the combined approach can serve as an effective intervention in clinical practice.

Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson’s disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3−/− mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Expression of genes encoding anti-inflammatory proteins and neuroprotective factors was reduced in the striatum of MPTP-treated mGlu3−/− mice. We also examined polymorphic variants of GRM3 (the mGlu3 receptor encoding gene) in 723 PD patients and 826 healthy controls. Two GRM3 haplotypes were associated with PD, and gene variants correlated with motor and non-motor signs. Interestingly, PD patients carrying each of the two haplotypes showed an impaired cortical plasticity in the paired associated stimulation paradigm of magnetic transcranial stimulation. These findings suggest that mGlu3 receptors are neuroprotective in mouse models of parkinsonism and shape mechanisms of cortical plasticity in PD.

Cerebellar Transcranial AC Stimulation Produces a Frequency-Dependent Bimodal Cerebellar Output Pattern.

Cerebellartranscranial alternating current stimulation (ctACS) has the potential to be an appealing, non-invasive treatment option for psychiatric and neurological disorders. However, realization of this potential has been limited by gaps in our knowledge of how ctACS affects cerebellar output on single cell and population levels. Previously, we showed that AC stimulation applied to the cerebellar surface produced a strong, frequency-dependent modulation of Purkinje cell (PC) and cerebellar nuclear (CN) cell activity. Here, to approximate more closely the ctACS conditions, we investigated how AC stimulation applied to the external skull surface overlying crus 1 altered PC and CN activity in anesthetized adult female Sprague-Dawley rats. PC and CN activity showed a frequency-dependent modulation in response to ctACS at frequencies ranging from 0.5 to 80Hz. A unimodal response was seen for most PCs across all frequencies, whereas most CN cells transitioned to bimodal patterns as stimulus frequency increased. The frequency-dependence of the phases of the local minima of the CN cell modulation were consistent with CN cells being driven synaptically by PC activity. Furthermore, comparison of responses with ipsilateral and contralateral placement of the stimulus electrode with respect to the recording site showed that the strength and pattern of the entrainment depended on the stimulus electrode location, suggesting thatctACS electrode placement could be used to target specific cerebellar output channels. In sum, the results show that transcranial stimulation of the cerebellar cortex can modulate cerebellar output, which has potential implications for its use in treating neurological and psychiatric disorders.

Investigation of the Effect of Transcranial Direct Current Stimulation on Inhibitory Control Deficits and Tendency Toward Stimulant Substance Use in Students

Objective: This study aims to examine whether transcranial direct current stimulation can effectively improve inhibitory control deficits and reduce students' tendency toward stimulant substance use. Methods and Materials: This research employed a quasi-experimental design with a pretest-posttest format. The study population included all 12th-grade students with stimulant substance use attending the Atieh Roshan Addiction Treatment Center in Shahriar in 2024. A total of approximately 100 12th-grade students were present at this center. From this population, 40 individuals were selected as the sample, based on inclusion and exclusion criteria, to conduct a targeted study. The statistical population consisted of all 12th-grade students aged 15 to 19 years with stimulant substance use in addiction treatment centers in Shahriar. Multivariate analysis of variance and SPSS26 software were used for data analysis. Findings: The results indicated the effectiveness of transcranial brain stimulation on emotional inhibition, aggression inhibition, mental rumination, benign inhibition, and the tendency toward stimulant substance use in students. Conclusion: It can be concluded that transcranial direct current stimulation can be effective in improving the psychological problems of individuals with substance use disorders.

Cortical Plasticity Induced by Pairing Primary Motor Cortex Transcranial Magnetic Stimulation With Subthalamic Nucleus Magneto-Acoustic Coupling Stimulation.

Paired cortical and deep stimulation has the potential to induce enhanced cortical plasticity. Ideally, such stimulation should be noninvasive and precisely controlled. A novel paired stimulation method, combining transcranial magnetic stimulation (TMS) with transcranial magneto-acoustic coupled stimulation (TMAS), named TMS-TMAS, was proposed to achieve such stimulations. Although the primary motor cortex (M1) is stimulated using TMS, the pulsed magnetic field is coupled with a focused ultrasound field to achieve TMAS-based focused electrical stimulation of the subthalamic nucleus (STN) via the magneto-acoustic coupling effect. Cortical plasticity is induced by precisely controlling the timing of magnetic pulse and ultrasound emissions based on spike timing-dependent plasticity (STDP). The experimental system achieved cortical-focused magnetic stimulation with a transverse resolution of 4.3 mm, a longitudinal resolution of 2.8 mm, and a magnetic field intensity of 1.6 T in the M1 region. Additionally, deep-focused electrical stimulation with a transverse resolution of 1.6 mm, a longitudinal resolution of 9.9 mm, and a coupled electric field intensity of 280 mV/m in the STN region was realized. In vivo animal experiments demonstrated that TMS-TMAS enhanced the amplitude of motor evoked potential (MEP) and reduced response latency. Simulation and experimental results confirmed that TMS-TMAS achieves high spatial resolution, noninvasive paired stimulation of the cortex and deep nuclei, and induces enhanced cortical plasticity when the stimulation sequence satisfies the STDP criteria. This method provides a promising approach for noninvasive paired stimulation and is expected to advance brain science research and the rehabilitation of neuropsychiatric disorders involving deep brain structures.

Low-intensity transcranial ultrasound stimulation inhibits epileptic seizures in motor cortex by modulating hippocampus neural activity.

Prior studies indicate that applying low-intensity transcranial ultrasound stimulation (TUS) to the hippocampus can suppress epileptic seizures. Nevertheless, it is unclear how TUS regulates hippocampal neural activity, and whether and how epileptic discharges in the motor cortex are suppressed by modulating hippocampal neural activity. To explore the answers of above questions, ultrasound was utilized to investigate the responses to the aforementioned inquiries by stimulating the hippocampus of mice with penicillin-induced epilepsy, while simultaneously recording the local field potentials (LFPs) in the hippocampus and the motor cortex (M1) throughout the experiment. The results showed that TUS (1) reduced the amplitude and the strength of the θ frequency band in LFPs in the hippocampus and M1, (2) decreased the coupling strength of the δ-γ, θ-γ and α-γ frequency bands in the hippocampus and M1, (3) weakened the correlation of neural activity between the hippocampus and M1. The above results indicated that TUS effectively suppressed abnormal slow neural oscillations in the hippocampus, had a significant decoupling effect on slow-fast neural oscillations, and reduced the correlation of hippocampus-cortical neural activity. TUS of the hippocampus may be through the hippocampus-cortical circuits to suppress abnormal neural firing activity in M1.

Efficacy of a 24-week long term transcranial pulse stimulation (TPS) on cognition and brain structure in older adults with mild cognitive impairment (MCI)Efficacy of a 24-week long term transcranial pulse stimulation (TPS) on cognition and brain structure in older adults with mild cognitive impairment (MCI)

Efficacy of a 24-week long term transcranial pulse stimulation (TPS) on cognition and brain structure in older adults with mild cognitive impairment (MCI)Efficacy of a 24-week long term transcranial pulse stimulation (TPS) on cognition and brain structure in older adults with mild cognitive impairment (MCI)

Effectiveness of sequential bilateral repetitive transcranial stimulation versus bilateral theta burst stimulation for patients with treatment-resistant depression (BEAT-D): A randomized non-inferiority clinical trial.

Bilateral repetitive transcranial magnetic stimulation (BL-rTMS) over the dorsolateral prefrontal cortex is effective for treatment-resistant depression (TRD). Owing to a shorter treatment time, bilateral theta burst stimulation (BL-TBS) can be more efficient protocol. The non-inferiority of BL-TBS to BL-rTMS was established in late-life TRD; however, this has not been determined in adults of other age groups. Therefore, we investigated the non-inferiority in efficacy of BL-TBS versus BL-rTMS for TRD across a wide range of ages in a randomized, single-blind, multicenter trial. The study included 180 participants with major depressive disorder (moderate or greater severity) who were unresponsive to at least one antidepressant treatment between September 2018 and July 2022. Following venlafaxine treatment, patients were randomly assigned to BL-rTMS or BL-TBS (1:1 ratio). The primary outcome was baseline-adjusted Montgomery-Åsberg Depression Rating Scale scores at 6 weeks. The non-inferiority margin of -3.86 was compared against the baseline-adjusted difference. Secondary outcomes included other depression rating scales. Seventy-seven patients were randomly assigned to BL-rTMS and 81 to BL-TBS, of whom 73 and 76 were assessed for the primary outcome, respectively. There was a -2.44 point difference, favoring BL-rTMS (one-tailed lower 95% CI=-4.19, p=0.091 for non-inferiority), and non-inferiority of BL-TBS was not established. However, non-inferiority was observed for secondary outcomes. The all-cause dropout rates and number of adverse effects were similar between them. Our study could not establish the non-inferiority of BL-TBS compared to BL-rTMS in terms of efficacy for patients with TRD across the adult lifespan.

Modulation of cortical oscillations by transcranial temporal interference stimulation (tTIS) targeting the primary somatosensory cortex

Modulation of cortical oscillations by transcranial temporal interference stimulation (tTIS) targeting the primary somatosensory cortex

Structural MRI-based Geometric Measures for Transcranial Brain Stimulation and Computational Simulation

Structural MRI-based Geometric Measures for Transcranial Brain Stimulation and Computational Simulation

A retrospective analysis of ultrasound neuromodulation therapy using transcranial pulse stimulation in 58 dementia patients.

Novel ultrasound neuromodulation techniques allow therapeutic brain stimulation with unmet precision and non-invasive targeting of deep brain areas. Transcranial pulse stimulation (TPS), a multifrequency sonication technique, is approved for the clinical treatment of Alzheimer's disease (AD). Here, we present the largest real-world retrospective analysis of ultrasound neuromodulation therapy in dementia (AD, vascular, mixed) and mild cognitive impairment (MCI). The consecutive sample involved 58 patients already receiving state-of-the-art treatment in an open-label, uncontrolled, retrospective study. TPS therapy typically comprises 10 sessions (range 8-12) with individualized MRI-based target areas defined according to brain pathology and individual pathophysiology. We compared the CERAD-Plus neuropsychological test battery results before and after treatment, with the CERAD Corrected Total Score ( CTS) as the primary outcome. Furthermore, we analyzed side effects reported by patients during the treatment period. CERAD Corrected Total Score (CTS) significantly improved (p=.017, d=.32) after treatment (Baseline: M=56.56, SD=18.56; Post-treatment: M=58.65, SD=19.44). The group of top-responders (top quartile) improved even by 9.8 points. Fewer than one-third of all patients reported any sensation during treatment. Fatigue and transient headaches were the most common, with no severe adverse events. The findings implicate TPS as a novel and safe add-on therapy for patients with dementia or MCI with the potential to further improve current state-of-the-art treatment results. Despite the individual benefits, further randomized, sham-controlled, longitudinal clinical trials are needed to differentiate the effects of verum and placebo.

Generating, validating and applying volume conductor models for electric field simulations to determine and optimize the brain regions targeting by transcranial brain stimulation

Generating, validating and applying volume conductor models for electric field simulations to determine and optimize the brain regions targeting by transcranial brain stimulation

Transcranial Pulse Stimulation (TPS) for the treatment of patients with Alzheimer's dementia: physical principles and state of the art

Transcranial Pulse Stimulation (TPS) for the treatment of patients with Alzheimer's dementia: physical principles and state of the art

Introducing a multifocal approach for transcranial pulse stimulation in alzheimer’s diasease: from long-term data to F-TOP2

Introducing a multifocal approach for transcranial pulse stimulation in alzheimer’s diasease: from long-term data to F-TOP2

Menstrual Migraine treat with transcranial direct stimulation - a principle of proof

Menstrual Migraine treat with transcranial direct stimulation - a principle of proof

Transcranial random noise stimulation of the bilateral parietal cortex enhances processing of visual cross-modal conflicts: A randomized controlled trial

Transcranial random noise stimulation of the bilateral parietal cortex enhances processing of visual cross-modal conflicts: A randomized controlled trial

Transcranial temporal interference stimulation to enhance motor learning and improve symptom severity in parkinson’s disease

Transcranial temporal interference stimulation to enhance motor learning and improve symptom severity in parkinson’s disease