Electrical or magnetic stimulation methods for brain or nerve modulation have been widely known for centuries, beginning with the Atlantic torpedo fish for the treatment of headaches in ancient Greece, followed by Luigi Galvani’s experiments with frog legs in baroque Italy, and leading to the interventional use of brain stimulation methods across Europe in the 19th century [...] Full article

As variable after effects have been observed following phasic muscle contraction prior to continuous theta-burst stimulation (cTBS), we here investigated two cTBS protocols (cTBS300 and cTBS600) in 20 healthy participants employing a pre-relaxed muscle condition including visual feedback on idle peripheral surface EMG activity. Furthermore, we assessed corticospinal excitability measures also from a pre-relaxed state to better understand the potential impact of these proposed contributors to TBS. Motor-evoked potential (MEP) magnitude changes were assessed for 30 min. The linear model computed across both experimental paradigms (cTBS300 and cTBS600) revealed a main effect of TIME COURSE (p = 0.044). Separate exploratory analysis for cTBS300 revealed a main effect of TIME COURSE (p = 0.031), which did not maintain significance after Greenhouse–Geisser correction (p = 0.073). For cTBS600, no main effects were observed. An exploratory analysis revealed a correlation between relative SICF at 2.0 ms (p = 0.006) and after effects (relative mean change) of cTBS600, which did not survive correction for multiple testing. Our findings thereby do not support the hypothesis of a specific excitability modulating effect of cTBS applied to the human motor-cortex in setups with pre-relaxed muscle conditions. Full article

Although transcranial direct current stimulation (tDCS) shows promise as a treatment for auditory verbal hallucinations in patients with schizophrenia, mechanisms through which tDCS may induce beneficial effects remain unclear. Evidence points to the involvement of neuronal plasticity mechanisms that are underpinned, amongst others, by brain-derived neurotrophic factor (BDNF) in its two main forms: pro and mature peptides. Here, we aimed to investigate whether tDCS modulates neural plasticity by measuring the acute effects of tDCS on peripheral mature BDNF levels in patients with schizophrenia. Blood samples were collected in 24 patients with schizophrenia before and after they received a single session of either active (20 min, 2 mA, n = 13) or sham (n = 11) frontotemporal tDCS with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. We compared the tDCS-induced changes in serum mature BDNF (mBDNF) levels adjusted for baseline values between the two groups. The results showed that active tDCS was associated with a significantly larger decrease in mBDNF levels (mean −20% ± standard deviation 14) than sham tDCS (−8% ± 21) (F = 5.387; p = 0.030; η² = 0.205). Thus, mature BDNF may be involved in the beneficial effects of frontotemporal tDCS observed in patients with schizophrenia. Full article

Background: Stroke affects the neuronal networks of the non-infarcted hemisphere. The central motor conduction time (CMCT) induced by transcranial magnetic stimulation (TMS) could be used to determine the conduction time of the corticospinal tract of the non-infarcted hemisphere after a stroke. Objectives: Our primary aim was to demonstrate the existence of prolonged CMCT in the non-infarcted hemisphere, measured within the first 48 h when compared to normative data, and secondly, if the severity of motor impairment of the affected upper limb was significantly associated with prolonged CMCTs in the non-infarcted hemisphere when measured within the first 2 weeks post stroke. Methods: CMCT in the non-infarcted hemisphere was measured in 50 patients within 48 h and at 11 days after a first-ever ischemic stroke. Patients lacking significant spontaneous motor recovery, so-called non-recoverers, were defined as those who started below 18 points on the FM-UE and showed less than 6 points (10%) improvement within 6 months. Results: CMCT in the non-infarcted hemisphere was prolonged in 30/50 (60%) patients within 48 h and still in 24/49 (49%) patients at 11 days. Sustained prolonged CMCT in the non-infarcted hemisphere was significantly more frequent in non-recoverers following FM-UE. Conclusions: The current study suggests that CMCT in the non-infarcted hemisphere is significantly prolonged in 60% of severely affected, ischemic stroke patients when measured within the first 48 h post stroke. The likelihood of CMCT is significantly higher in non-recoverers when compared to those that show spontaneous motor recovery early post stroke. Full article

Previous investigations have reported on the motor benefits and safety of chronic extradural motor cortex stimulation (EMCS) for patients with Parkinson’s disease (PD), but studies addressing the long-term clinical outcome are still lacking. In this study, nine consecutive PD patients who underwent EMCS were prospectively recruited, with a mean follow-up time of 5.1 ± 2.5 years. As compared to the preoperatory baseline, the Unified Parkinson’s Disease Rating Scale (UPDRS)-III in the off-medication condition significantly decreased by 13.8% at 12 months, 16.1% at 18 months, 18.4% at 24 months, 21% at 36 months, 15.6% at 60 months, and 8.6% at 72 months. The UPDRS-IV decreased by 30.8% at 12 months, 22.1% at 24 months, 25% at 60 months, and 36.5% at 72 months. Dopaminergic therapy showed a progressive reduction, significant at 60 months (11.8%). Quality of life improved by 18.0% at 12 months, and 22.4% at 60 months. No surgical complication, cognitive or behavioral change occurred. The only adverse event reported was an infection of the implantable pulse generator pocket. Even in the long-term follow-up, EMCS was shown to be a safe and effective treatment option in PD patients, resulting in improvements in motor symptoms and quality of life, and reductions in motor complications and dopaminergic therapy. Full article

Transcranial alternating current stimulation (tACS) has emerged as a promising technique to non-invasively modulate the endogenous oscillations in the human brain. Despite its clinical potential to be applied in routine rehabilitation therapies, the underlying modulation mechanism has not been thoroughly understood, especially for patients with neurological disorders, including stroke. In this study, we aimed to investigate the frequency-specific stimulation effect of tACS in chronic stroke. Thirteen chronic stroke patients underwent tACS intervention, while resting-state functional magnetic resonance imaging (fMRI) data were collected under various frequencies (sham, 10 Hz and 20 Hz). The graph theoretical analysis indicated that 20 Hz tACS might facilitate local segregation in motor-related regions and global integration at the whole-brain level. However, 10 Hz was only observed to increase the segregation from whole-brain level. Additionally, it is also observed that, for the network in motor-related regions, the nodal clustering characteristic was decreased after 10 Hz tACS, but increased after 20 Hz tACS. Taken together, our results suggested that tACS in various frequencies might induce heterogeneous modulation effects in lesioned brains. Specifically, 20 Hz tACS might induce more modulation effects, especially in motor-related regions, and they have the potential to be applied in rehabilitation therapies to facilitate neuromodulation. Our findings might shed light on the mechanism of neural responses to tACS and facilitate effectively designing stimulation protocols with tACS in stroke in the future. Full article

Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes. PDR-related retinal hemorrhages often lead to severe vision loss. The main goals of management are to prevent visual impairment progression and improve residual vision. We explored the potential of transcranial direct current stimulation (tDCS) to enhance residual vision. tDCS applied to the primary visual cortex (V1) may improve visual input processing from PDR patients’ retinas. Eleven PDR patients received cathodal tDCS stimulation of V1 (1 mA for 10 min), and another eleven patients received sham stimulation (1 mA for 30 s). Visual acuity (logarithm of the minimum angle of resolution (LogMAR) scores) and number acuity (reaction times (RTs) and accuracy rates (ARs)) were measured before and immediately after stimulation. The LogMAR scores and the RTs of patients who received cathodal tDCS decreased significantly after stimulation. Cathodal tDCS has no significant effect on ARs. There were no significant changes in the LogMAR scores, RTs, and ARs of PDR patients who received sham stimulation. The results are compatible with our proposal that neuronal noise aggravates impaired visual function in PDR. The therapeutic effect indicates the potential of tDCS as a safe and effective vision rehabilitation tool for PDR patients. Full article

This outcome assessor-blinded, randomized controlled clinical trial investigated the effects of electroacupuncture combined with computer-based cognitive rehabilitation (EA-CCR) on mild cognitive impairment (MCI). A per-protocol analysis was employed to compare the efficacy of EA-CCR to that of computer-based cognitive rehabilitation (CCR). Thirty-two patients with MCI completed the trial (EA-CCR group, 16; CCR group, 16). Patients received EA-CCR or CCR treatment once daily three days per week for eight weeks. Outcome (primary, ADAS-K-cog; secondary, MoCA-K, CES-D, K-ADL, K-IADL, and EQ-5D-5L) measurements were performed at baseline (week 0), at the end of the intervention (week 8), and at 12 weeks after completion of the intervention (week 20). Both groups showed significant changes in ADAS-K-cog score (EA-CCR, p < 0.001; CCR, p < 0.001) and MoCA-K (EA-CCR, p < 0.001; CCR, p < 0.001). Only the EA-CCR group had a significant change in CES-D (p = 0.024). No significant differences in outcomes and in the results of a subanalysis based on age were noted between the groups. These results indicate that EA-CCR and CCR have beneficial effects on improving cognitive function in patients with MCI. However, electroacupuncture in EA-CCR showed no positive add-on effects on improving cognitive function, depression, activities of daily living, and quality of life in patients with MCI. Full article

Various studies suggested alterations in pain perception in psychiatric disorders, such as borderline personality disorder (BPD) and major depression (MD). We previously investigated affective components of pain perception in BPD compared to healthy controls (HC) by increasing aversive stimulus intensities using repetitive peripheral magnetic stimulation (rPMS) and observed alterations in emotional rather than somatosensory components in BPD. However, conclusions on disorder specific alterations in these components of pain perception are often limited due to comorbid depression and medication in BPD. Here, we compared 10 patients with BPD and comorbid MD, 12 patients with MD without BPD, and 12 HC. We applied unpleasant somatosensory stimuli with increasing intensities by rPMS and assessed pain threshold (PT), cutaneous sensation, emotional valence, and arousal by a Self-Assessments Manikins scale. PTs in BPD were significantly higher compared to HC. The somatosensory discrimination of stimulus intensities did not differ between groups. Though elevated rPMS intensities led to increased subjective aversion and arousal in MD and HC, these emotional responses among intensity levels remained unchanged in BPD. Our data give further evidence for disorder-specific alterations in emotional components of pain perception in BPD with an absent emotional modulation among varying aversive intensity levels. Full article

Background: Low intensity, high-frequency transcranial alternating current stimulation (tACS) applied over the motor cortex decreases the amplitude of motor evoked potentials. This double-blind, placebo-controlled parallel group study aimed to test the efficacy of this method for acute management of migraines. Methods: The patients received either active (0.4 mA, 140 Hz) or sham stimulation for 15 min over the visual cortex with the number of terminated attacks two hours post-stimulation as the primary endpoint, as a home therapy option. They were advised to treat a maximum of five migraine attacks over the course of six weeks. Results: From forty patients, twenty-five completed the study, sixteen in the active and nine in the sham group with a total of 102 treated migraine attacks. The percentage of terminated migraine attacks not requiring acute rescue medication was significantly higher in the active (21.5%) than in the sham group (0%), and the perceived pain after active stimulation was significantly less for 2–4 h post-stimulation than after sham stimulation. Conclusion: tACS over the visual cortex has the potential to terminate migraine attacks. Nevertheless, the high drop-out rate due to compliance problems suggests that this method is impeded by its complexity and time-consuming setup. Full article

Patients with bilateral vestibular hypofunction (BVH) often suffer from imbalance, gait problems, and oscillopsia. Noisy galvanic vestibular stimulation (GVS), a technique that non-invasively stimulates the vestibular afferents, has been shown to enhance postural and walking stability. However, no study has investigated how it affects stability and neural activities while standing and walking with a 2 Hz head yaw turning. Herein, we investigated this issue by comparing differences in neural activities during standing and walking with a 2 Hz head turning, before and after noisy GVS. We applied zero-mean gaussian white noise signal stimulations in the mastoid processes of 10 healthy individuals and seven patients with BVH, and simultaneously recorded electroencephalography (EEG) signals with 32 channels. We analyzed the root mean square (RMS) of the center of pressure (COP) sway during 30 s of standing, utilizing AMTI force plates (Advanced Mechanical Technology Inc., Watertown, MA, USA). Head rotation quality when walking with a 2 Hz head yaw, with and without GVS, was analyzed using a VICON system (Vicon Motion Systems Ltd., Oxford, UK) to evaluate GVS effects on static and dynamic postural control. The RMS of COP sway was significantly reduced during GVS while standing, for both patients and healthy subjects. During walking, 2 Hz head yaw movements was significantly improved by noisy GVS in both groups. Accordingly, the EEG power of theta, alpha, beta, and gamma bands significantly increased in the left parietal lobe after noisy GVS during walking and standing in both groups. GVS post-stimulation effect changed EEG activities in the left and right precentral gyrus, and the right parietal lobe. After stimulation, EEG activity changes were greater in healthy subjects than in patients. Our findings reveal noisy GVS as a non-invasive therapeutic alternative to improve postural stability in patients with BVH. This novel approach provides insight to clinicians and researchers on brain activities during noisy GVS in standing and walking conditions in both healthy and BVH patients. Full article

In contrast to motor symptoms, non-motor symptoms in Parkinson’s disease (PD) are often poorly recognized and inadequately treated. Fatigue is one of the most common non-motor symptoms in PD and affects a broad range of everyday activities, causes disability, and substantially reduces the quality of life. It occurs at every stage of PD, and once present, it often persists and worsens over time. PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. However, despite its clinical significance, little progress has been made in understanding the causes of Parkinson’s disease-related fatigue (PDRF) and developing effective treatment options, which argues strongly for a greater effort. Transcranial direct current stimulation (tDCS) is a technique to non-invasively modulate cortical excitability by delivering low electrical currents to the cerebral cortex. In the past, it has been consistently evidenced that tDCS has the ability to induce neuromodulatory changes in the motor, sensory, and cognitive domains. Importantly, recent data present tDCS over the frontal cortex as an effective therapeutic option to treat fatigue in patients suffering from multiple sclerosis (MS). The current opinion paper reviews recent data on PDRF and the application of tDCS for the treatment of fatigue in neuropsychiatric disorders to further develop an idea of using frontal anodal tDCS as a potential therapeutic strategy to alleviate one of the most common and severe non-motor symptoms of PD. Full article

Biological effects of extremely low-frequency magnetic field (ELF-MF) and its consequences on human health have become the subject of important and recurrent public debate. ELF-MF evokes cell/organism responses that are characteristic to a general stress reaction, thus it can be regarded as a stress factor. Exposure to ELF-MF “turns on” different intracellular mechanisms into both directions: compensatory or deleterious ones. ELF-MF can provoke morphological and physiological changes in stress-related systems, mainly nervous, hormonal, and immunological ones. This review summarizes the ELF-MF-mediated changes at various levels of the organism organization. Special attention is placed on the review of literature from the last decade. Most studies on ELF-MF effects concentrate on its negative influence, e.g., impairment of behavior towards depressive and anxiety disorders; however, in the last decade there was an increase in the number of research studies showing stimulating impact of ELF-MF on neuroplasticity and neurorehabilitation. In the face of numerous studies on the ELF-MF action, it is necessary to systematize the knowledge for a better understanding of the phenomenon, in order to reduce the risk associated with the exposure to this factor and to recognize the possibility of using it as a therapeutic agent. Full article