Non-invasive Neurostimulation Research Articles

Evaluating the Efficacy of Transcranial Magnetic Stimulation in Symptom Relief and Cognitive Function in Obsessive–Compulsive Disorder, Substance Use Disorder, and Depression: An Insight from a Naturalistic Observational Study

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven’s matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols.

Transcranial photobiomodulation for neurodevelopmental disorders: a narrative review.

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs. A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: "photobiomodulation", "PBM", "neurodevelopmental disorders", "NDD", and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded. Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635-905nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation. t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.

Spinal Cord Transcutaneous Stimulation in Cervical Spinal Cord Injury: A Review Examining Upper Extremity Neuromotor Control, Recovery Mechanisms, and Future Directions.

Cervical spinal cord injury (SCI) results in significant sensorimotor impairments below the injury level, notably in the upper extremities (UEs), impacting daily activities and quality of life. Regaining UE function remains the top priority for individuals post-cervical SCI. Recent advances in understanding adaptive plasticity within the sensorimotor system have led to the development of novel non-invasive neurostimulation strategies, such as spinal cord transcutaneous stimulation (scTS), to facilitate UE motor recovery after SCI. This comprehensive review investigates the neuromotor control of UE, the typical recovery trajectories following SCI, and the therapeutic potential of scTS to enhance UE motor function in individuals with cervical SCI. Although limited in number with smaller sample sizes, the included research articles consistently suggest that scTS, when combined with task-specific training, improves voluntary control of arm and hand function and sensation. Further, the reported improvements translate to the recovery of various UE functional tasks and positively impact the quality of life in individuals with cervical SCI. Several methodological limitations, including stimulation site selection and parameters, training strategies, and sensitive outcome measures, require further advancements to allow successful translation of scTS from research to clinical settings. This review also summarizes the current literature and proposes future directions to support establishing approaches for scTS as a viable neuro-rehabilitative tool.

Pharmacotherapy and noninvasive neurostimulation for neuropathic pain

Neuropathic pain poses a significant challenge due to its complex mechanisms, necessitating specific treatments. In recent decades, significant progress has been made in the clinical research of neuropathic pain, marking a shift from empirical strategies to evidence-based medicine in its management. This review outlines both pharmacological and non-pharmacological interventions. Antidepressants (tricyclic and serotonin-noradrenaline reuptake inhibitors), antiepileptics (gabapentin, pregabalin), and topical agents constitute the main pharmacological treatments. These approaches target peripheral or central mechanisms associated with neuropathic pain. Noninvasive neurostimulation, including transcutaneous electrical nerve stimulation (TENS) and repetitive transcranial magnetic stimulation (rTMS), provides non-pharmacological alternatives. However, challenges persist in effectively targeting existing medications and developing drugs that act on novel targets, necessitating innovative therapeutic strategies.

Abstract WP14: Photobiomodulation Treatment Enhancesand Sustains Neurogenesis Following Acute Ischemic Stroke

Rationale: Previous work has indicated that photobiomodulation (PBM), may provide neuroprotection and improve neurological function after acute ischemic stroke. However, the underlying mechanism remains unclear. The present study was performed to examine whether PBM, a noninvasive neurostimulation technique, promotes neurogenesis in a middle cerebral artery occlusion (MCAO) stroke rat model. Methods: Beginning 6 h after MCAO, once-daily 2-min PBM treatments(808 nm) were applied to the infarcted hemisphere for 7 consecutive days. Samples were collected 7 days and 14 days after MCAO stroke. Fluorescent labeling, Western blotting, and behavioral tests were performed accordingly. Results: We found that PBM-treated animals displayed improved motor and sensory functions. PBM treatment significantly expanded the pool of neural progenitor cell (NPC) and newly generated immature neurons in the cortical peri-infarct region after acute ischemic stroke. Application of PBM strikingly diminished the MCAO-induced loss of NPCs and newly-formed neurons. In addition, the amount of newly generated mature neurons in the peri-infarct zone was significantly promoted by PBM treatment. Intriguingly, PBM reduced reactive gliogenesis significantly while promoting oligodendrogenesis and preserving myelination. Mechanistic studies uncovered that PBM enhances the expression of brain-derived neurotrophic factor (BDNF) and initiates the activation of the BDNF/TrkB signaling pathway. Conclusions: Our findings indicate that PBM promotes neurogenesis and functional recovery through stimulating NPC proliferation, reducing NPC and immature neuron cell death, and tamping excessive gliogenesis. These effects were due, in part, to the upregulated release of trophic factors. These findings support PBM as an effective neuroregenerative treatment for acute ischemic stroke. Keywords: Ischemic stroke, Photobiomodulation (PBM), Neurogenesis, Functional recovery, Neurotrophic factors

Molecular Insights into Transcranial Direct Current Stimulation Effects: Metabolomics and Transcriptomics Analyses.

Transcranial direct current stimulation (tDCS) is an evolving non-invasive neurostimulation technique. Despite multiple studies, its underlying molecular mechanisms are still unclear. Several previous human studies of the effect of tDCS suggest that it generates metabolic effects. The induction of metabolic effects by tDCS could provide an explanation for how it generates its long-term beneficial clinical outcome. Given these hints of tDCS metabolic effects, we aimed to delineate the metabolic pathways involved in its mode of action. To accomplish this, we utilized a broad analytical approach of co-analyzing metabolomics and transcriptomic data generated from anodal tDCS in rat models. Since no metabolomic dataset was available, we performed a tDCS experiment of bilateral anodal stimulation of 200 µA for 20 min and for 5 consecutive days, followed by harvesting the brain tissue below the stimulating electrode and generating a metabolomics dataset using LC-MS/MS. The analysis of the transcriptomic dataset was based on a publicly available dataset. Our analyses revealed that tDCS alters the metabolic profile of brain tissue, affecting bioenergetic-related pathways, such as glycolysis and mitochondrial functioning. In addition, we found changes in calcium-related signaling. We conclude that tDCS affects metabolism by modulating energy production-related processes. Given our findings concerning calcium-related signaling, we suggest that the immediate effects of tDCS on calcium dynamics drive modifications in distinct metabolic pathways. A thorough understanding of the underlying molecular mechanisms of tDCS has the potential to revolutionize its applicability, enabling the generation of personalized medicine in the field of neurostimulation and thus contributing to its optimization.

New possibilities of overcoming pharmacoresistance in epilepsy

Despite the presence of antiepileptic drugs with different mechanisms of action and application points, almost a third of patients still remain resistant to drug therapy. In such patients, the risk of physical and mental injuries, depression, premature death increases, and the quality and standard of living decreases.Objective. To study the mechanisms of formation of pharmacoresistance in epilepsy and to evaluate possible ways to overcome it based on the analysis of current scientific publications containing information on this topic.Results. The proposed pathophysiological mechanisms of the formation of drug resistance reflect the target hypothesis, the carrier hypothesis, pharmacokinetic theory and neural network theory. However, they are based on preclinical studies and do not have a comprehensive explanation for the appearance of this phenomenon. Surgical treatment remains the most studied and most commonly used approach. Both the usual resection of the epileptogenic part of the brain and new less crippling interventions are used: laser ablation and stereotactic radiosurgery. As an alternative, polytherapy schemes, invasive and non-invasive neurostimulation techniques, and diet therapy can be considered.Conclusions. Insensitivity to antiepileptic drugs remains a major problem in epileptology, and to overcome it, new methods are being sought and developed to influence the presumed pathogenetic targets of pharmacoresistant epileptogenesis. Vagus, deep, transcranial neurostimulation, stereotactic surgery, and laser ablation should be considered as new safe and potentially effective techniques.

Challenges and opportunities in testing sensorimotor processing with tendon vibration and transcranial magnetic stimulation in subacromial impingement syndrome: A case series.

Non-invasive neurostimulation like muscle tendon vibration (VIB) and transcranial magnetic stimulation (TMS) can provide valuable insights on mechanisms underlying sensorimotor dysfunctions. However, their feasibility in the context of painful musculoskeletal disorders like shoulder impingement syndrome (SIS) remain uncertain. The present work used a case series design including 15 participants with SIS, as well as a secondary group-based analysis comparing participants with SIS to 15 healthy counterparts. Proprioceptive processing was tested by VIB-induced kinesthetic illusions of shoulder abduction, and TMS tested corticospinal excitability of the upper trapezius. Detailed individual data were collected, including any technical challenges and feasibility issues encountered. VIB was in general well-tolerated and elicited a perceptible kinesthetic illusion in 13 participants with SIS and 14 controls. TMS presented with several challenges related to discomfort, fear-related behaviors, technical problems and high motor thresholds, especially in participants with SIS. It was only possible to collect all TMS measures in 5 participants with SIS (for both the painful and non/less-painful sides), in 7 controls on their dominant side and 10 controls on the non-dominant side. The only significant group-based analysis was a lower illusion speed/amplitude on the painful versus non-painful side in persons with SIS (p = 0.035). Our study provides preliminary data on challenges encountered with TMS and VIB of trunk/proximal muscle in persons with SIS and healthy counterparts. It might help future studies to better address those challenges beforehand and improve the overall feasibility and impact of neurostimulation tools in musculoskeletal disorders.

Ultrasound Deep Brain Stimulation Regulates Food Intake and Body Weight in Mice.

Given the widespread occurrence of obesity, new strategies are urgently needed to prevent, halt and reverse this condition. We proposed a noninvasive neurostimulation tool, ultrasound deep brain stimulation (UDBS), which can specifically modulate the hypothalamus and effectively regulate food intake and body weight in mice. Fifteen-min UDBS of hypothalamus decreased 41.4% food intake within 2 hours. Prolonged 1-hour UDBS significantly decreased daily food intake lasting 4 days. UDBS also effectively restrained body weight gain in leptin-receptor knockout mice (Sham: 96.19%, UDBS: 58.61%). High-fat diet (HFD) mice treated with 4-week UDBS (15 min / 2 days) reduced 28.70% of the body weight compared to the Sham group. Meanwhile, UDBS significantly modulated glucose-lipid metabolism and decreased the body fat. The potential mechanism is that ultrasound actives pro-opiomelanocortin (POMC) neurons in the hypothalamus for reduction of food intake and body weight. These results provide a noninvasive tool for controlling food intake, enabling systematic treatment of obesity.

Effects of transcranial direct current stimulation over human motor cortex on cognitive-motor and sensory-motor functions.

The primary motor cortex (M1) is broadly acknowledged for its crucial role in executing voluntary movements. Yet, its contributions to cognitive and sensory functions remain largely unexplored. Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation method that can modify brain activity, thereby enabling the establishment of a causal link between M1 activity and behavior. This study aimed to investigate the online effects of tDCS over M1 on cognitive-motor and sensory-motor functions. Sixty-four healthy participants underwent either anodal or sham tDCS while concurrently performing a set of standardized robotic tasks. These tasks provided sensitive and objective assessments of brain functions, including action selection, inhibitory control, cognitive control of visuomotor skills, proprioceptive sense, and bimanual coordination. Our results revealed that anodal tDCS applied to M1 enhances decision-making capacity in selecting appropriate motor actions and avoiding distractors compared to sham stimulation, suggesting improved action selection and inhibitory control capabilities. Furthermore, anodal tDCS reduces the movement time required to accomplish bimanual movements, suggesting enhanced bimanual performance. However, we found no impact of anodal tDCS on cognitive control of visuomotor skills and proprioceptive sense. This study suggests that augmenting M1 activity via anodal tDCS influences cognitive-motor and sensory-motor functions in a task-dependent manner.

Safety and Feasibility of Functional Repetitive Neuromuscular Magnetic Stimulation of the Gluteal Muscles in Children and Adolescents with Bilateral Spastic Cerebral Palsy.

Background: For children and adolescents affected by bilateral spastic cerebral palsy (BSCP), non-invasive neurostimulation with repetitive neuromuscular magnetic stimulation (rNMS) combined with physical exercises, conceptualized as functional rNMS (frNMS), represents a novel treatment approach. Methods: In this open-label study, six children and two adolescents (10.4 ± 2.5 years) with BSCP received a frNMS intervention targeting the gluteal muscles (12 sessions within 3 weeks). Results: In 77.1% of the sessions, no side effects were reported. In 16.7%, 6.3% and 5.2% of the sessions, a tingling sensation, feelings of pressure/warmth/cold or very shortly lasting pain appeared, respectively. frNMS was highly accepted by families (100% adherence) and highly feasible (97.9% of treatment per training protocol). A total of 100% of participants would repeat frNMS, and 87.5% would recommend it. The Canadian Occupational Performance Measure demonstrated clinically important benefits for performance in 28% and satisfaction in 42% of mobility-related tasks evaluated by caregivers for at least one follow-up time point (6 days and 6 weeks post intervention). Two patients accomplished goal attainment for one mobility-related goal each. One patient experienced improvement for both predefined goals, and another participant experienced improvement in one and outreach of the other goal as assessed with the goal attainment scale. Conclusions: frNMS is a safe and well-accepted neuromodulatory approach that could improve the quality of life, especially in regard to activity and participation, of children and adolescents with BSCP. Larger-scaled studies are needed to further explore the effects of frNMS in this setting.

B - 52 Effects of rTMS Treatment on Attention Measured by the CANTAB Rapid Visual Information Processing Module.

Traumatic brain injury (TBI) has been associated with decreased performance in sustained attention tasks (Sinclair et al., 2013). Non-invasive neurostimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) may be utilized to improve cognitive outcomes, however there is uncertainty about which cognitive outcomes should be investigated (Clark & Parasuraman, 2014; Donaldson et al., 2015). The present study examines the observed enhancements in sustained attention related to rTMS administered to older adults with TBI. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB), a commonly used assessment instrument in research settings that offers various modules for measuring neurocognitive functions (CDC). Veterans and civilians were enrolled (n = 28; mild and moderate TBI; mean age = 62.25) in either placebo or an active group. Participants received neuropsychological assessment at baseline, after 20 rTMS treatments, and at six month follow up. Participants were administered the CANTAB Rapid Visual Information Processing (RVIP) module to assess sustained attention after active rTMS or sham treatment. Findings revealed that the active rTMS treatment group had a lower RVIPPFA (n = 12; M = 0.003; SD = 0.003) compared to the sham group (n = 16; M = 0.02; SD = 0.06), indicating a potential improvement in visual sustained attention. A moderate effect size was observed between the two groups (Cohen's d = 0.48). The results suggest that rTMS treatment could potentially enhance cognitive performance, specifically visual sustained attention, in older adults. Further research is warranted to investigate the impact of rTMS on sustained attention and its clinical implications.

Functional Repetitive Neuromuscular Magnetic Stimulation (frNMS) Targeting the Tibialis Anterior Muscle in Children with Upper Motor Neuron Syndrome: A Feasibility Study.

Non-invasive neurostimulation as an adjunctive intervention to task-specific motor training is an approach to foster motor performance in patients affected by upper motor neuron syndrome (UMNS). Here, we present first-line data of repetitive neuromuscular magnetic stimulation (rNMS) in combination with personalized task-specific physical exercises targeting the tibialis anterior muscle to improve ankle dorsiflexion (functional rNMS (frNMS)). The main objective of this pilot study was to assess the feasibility in terms of adherence to frNMS, safety and practicability of frNMS, and satisfaction with frNMS. First, during 10 training sessions, only physical exercises were performed (study period (SP) A). After a 1 week break, frNMS was delivered during 10 sessions (SPC). Twelve children affected by UMNS (mean age 8.9 ± 1.6 years) adhered to 93% (SPA) and 94% (SPC) of the sessions, and omittance was not related to the intervention itself in any case. frNMS was safe (no AEs reported in 88% of sessions, no AE-related discontinuation). The practicability of and satisfaction with frNMS were high. Patient/caregiver-reported outcomes revealed meaningful benefits on the individual level. The strength of the ankle dorsiflexors (MRC score) clinically meaningfully increased in four participants as spasticity of ankle plantar flexors (Tardieu scores) decreased in four participants after SPC. frNMS was experienced as a feasible intervention for children affected by UMNS. Together with the beneficial effects achieved on the individual level in some participants, this first study supports further real-world, large-scale, sham-controlled investigations to investigate the specific effects and distinct mechanisms of action of frNMS.

Current Neurostimulation Therapies for Chronic Pain Conditions.

Neurostimulation treatment options have become more commonly used for chronic pain conditions refractory to these options. In this review, we characterize current neurostimulation therapies for chronic pain conditions and provide an analysis of their effectiveness and clinical adoption. This manuscript will inform clinicians of treatment options for chronic pain. Non-invasive neurostimulation includes transcranial direct current stimulation and repetitive transcranial magnetic stimulation, while more invasive options include spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), dorsal root ganglion stimulation, motor cortex stimulation, and deep brain stimulation. Developments in transcranial direct current stimulation, repetitive transcranial magnetic stimulation, spinal cord stimulation, and peripheral nerve stimulation render these modalities most promising for the alleviating chronic pain. Neurostimulation for chronic pain involves non-invasive and invasive modalities with varying efficacy. Well-designed randomized controlled trials are required to delineate the outcomes of neurostimulatory modalities more precisely.

Effects of transcutaneous auricular vagus nerve stimulation on P300 magnitudes and salivary alpha-amylase during an auditory oddball task

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neurostimulation technique that is thought to modulate noradrenergic activity. Previous studies have demonstrated inconsistent effects of taVNS on noradrenergic activity, which is possibly due to insufficient statistical power, suboptimal stimulation parameter settings, and data collection procedures. In this preregistered within-subject experiment, 44 healthy participants received taVNS and sham (earlobe) stimulation during two separate experimental sessions. Stimulation intensity was individually calibrated to the maximum level below pain. During each session, participants received the stimulation continuously ten minutes before an auditory novelty oddball task till the end of the experimental session. The P3b component of the event-related potential served as a marker of phasic noradrenergic activity, whereas P3a magnitude was explored as an index of dopaminergic activity. Salivary alpha-amylase (sAA) was measured as an index of tonic noradrenergic activity before and at the end of the stimulation. The taVNS and sham conditions did not differ in P3a or P3b magnitudes, nor sAA secretion. These findings call into question whether taVNS, administered continuously at high, nonpainful stimulation intensities, reliably augments noradrenergic activity via the vagus nerve.

Mild Cognitive Impairment – Prospects for Prognosis and Management

The term mild cognitive impairment (MCI) has traditionally been used to refer to a transitional period between normal cognitive function and clinically probable Alzheimer’s disease (AD). Many studies report high reversion rates, however, with some 30% to 50% of those diagnosed with MCI reverting to “normal” cognition at subsequent follow-up. The detection of differentiable predisposing factors, reflected in the dichotomy between the annual reversion rate to normal cognition and the conversion rate to dementia, indicates that there are modifiable factors that may be contributing to cognitive decline. The clinical prospect for dementia and the presence of these predisposing factors have together made a strong case for early diagnosis and therapeutic intervention. Current efforts seek to identify tools capable of resolving the causal ambiguities inherent in MCI and to develop therapeutic avenues addressing such underlying aspects before long lasting and irreversible cognitive loss. This review explores three arenas for which there is especial promise for determining and modulating prognosis: in the diagnostic realm, novel neuroimaging procedures and biomarkers and, in the domain of therapy, network based non-invasive neurostimulation therapies. Particular examples include novel structural and dynamical MRI procedures for assessing connectivity and its alterations during disease, inflammation and miRNA markers, and non-invasive procedures for rehabilitating deteriorating brain functions. The advances occurring in these select areas indicate that the determination of MCI’s multi-etiology is a realistic goal that can ground prognosis assessment and therapeutic outcome.

Design and Evaluation of a Potential Non-Invasive Neurostimulation Strategy for Treating Persistent Anosmia in Post-COVID-19 Patients.

A new pandemic was declared at the end of 2019 because of coronavirus disease 2019 (COVID-19). One of the effects of COVID-19 infection is anosmia (i.e., a loss of smell). Unfortunately, this olfactory dysfunction is persistent in around 5% of the world's population, and there is not an effective treatment for it yet. The aim of this paper is to describe a potential non-invasive neurostimulation strategy for treating persistent anosmia in post-COVID-19 patients. In order to design the neurostimulation strategy, 25 subjects who experienced anosmia due to COVID-19 infection underwent an olfactory assessment while their electroencephalographic (EEG) signals were recorded. These signals were used to investigate the activation of brain regions during the olfactory process and identify which regions would be suitable for neurostimulation. Afterwards, 15 subjects participated in the evaluation of the neurostimulation strategy, which was based on applying transcranial direct current stimulation (tDCS) in selected brain regions related to olfactory function. The results showed that subjects with lower scores in the olfactory assessment obtained greater improvement than the other subjects. Thus, tDCS could be a promising option for people who have not fully regained their sense of smell following COVID-19 infection.

Transcranial direct current stimulation—current level of evidence and potential application scenarios—English version

In Europe, anterior thalamic stimulation, vagus nerve stimulation, and focal cortex stimulation are the only approved neurostimulation therapies for drug-resistant epilepsy. However, they are invasive and have limited availability and effectiveness. First reports on the use of transcranial direct current stimulation (tDCS) in epilepsy are promising and give hope for an alternative, non-invasive neurostimulation modality. What is the current level of evidence for the use of tDCS in epilepsy and what could be potential application scenarios? Safety and effectiveness data on the use of tDCS in epilepsy were summarized based on a PubMed literature search. Cathodal tDCS is associated with only mild and transient side effects like paresthesia, tiredness, or difficulties in concentrating. There is no evidence for seizure induction under cathodal tDCS. A single stimulation over 20 min can already induce a seizure frequency reduction of more than 40% in the four subsequent weeks, with effect enhancement under repeated and spaced stimulation using an interstimulation interval of 9–20 min. tDCS would not only extent the spectrum of treatments for epilepsy, it could also allow for reduction of the drug and side-effect load and potentially predict the treatment outcome for implantable devices. The literature data confirm the safe and effective use of cathodal tDCS in patients with drug-resistant epilepsy. Further studies are required to optimize stimulation parameters, to improve effectiveness, and to verify safety and effectiveness aspects in long-term application.

Non-pharmacological Therapies of Dementia - an Update

Non-pharmacological Therapies of Dementia - an Update Abstract: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. This is an up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use according to the current state of research and the recommendations of AWMF S3 guideline "dementia". The most important interventions from this therapeutic spectrum are cognitive stimulation to maintain cognitive functioning, physical activation, and creative therapeutic offers to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

Gamma neuromodulation improves episodic memory and its associated network in amnestic mild cognitive impairment: a pilot study

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer’s disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer’s disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network.