Efficacy Of Stimulation Research Articles

New Perspectives for Spinal Cord Stimulation in Parkinson's Disease-Associated Gait Impairment: A Systematic Review.

Parkinson's Disease is a neurodegenerative disorder manifesting itself as a hypokinetic movement impairment with postural instability and gait disturbance. In case of failure and/or limited response, deep brain stimulation has been established as an alternative and effective treatment modality. However, a subset of PD patients with gait impairment represents a therapeutic challenge. A systematic review (2000-2023) was performed using PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases to determine the efficacy, stimulation waveform/parameters, spine level, and outcome measures of spinal cord stimulation using different waveforms in PD patients with and without chronic pain. Spinal cord stimulation responsiveness was assessed within the pre-defined follow-up period in three groups (short-term follow-up = 0-3 months; intermediate follow-up = 3-12 months; and long-term follow-up = more than 12 months). In addition, we briefly outline alternative neurostimulation therapies and the most recent developments in closed-loop spinal cord stimulation relevant to PD. In summary, 18 publications and 70 patients from uncontrolled observational trials were included, with low-quality evidence and conflicting findings. First and foremost, the currently available data do not support the use of spinal cord stimulation to treat PD-related gait disorders but have confirmed its usefulness for PD-associated chronic pain.

Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor.

Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies. To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor. Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported. Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6months) and long-term follow-up (up to 6years). No adverse events occurred. In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.

Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

Vagus nerve electroneurogram-based detection of acute kainic acid induced seizures.

Seizures produce autonomic symptoms, mainly sympathetic but also parasympathetic in origin. Within this context, the vagus nerve is a key player as it carries information from the different organs to the brain and vice versa. Hence, exploiting vagal neural traffic for seizure detection might be a promising tool to improve the efficacy of closed-loop Vagus Nerve Stimulation. This study developed a VENG detection algorithm that effectively detects seizures by emphasizing the loss of spontaneous rhythmicity associated with respiration in acute intrahippocampal Kainic Acid rat model. Among 20 induced seizures in six anesthetized rats, 13 were detected (sensitivity: 65%, accuracy: 92.86%), with a mean VENG-detection delay of 25.3 ± 13.5 s after EEG-based seizure onset. Despite variations in detection parameters, 7 out of 20 seizures exhibited no ictal VENG modifications and remained undetected. Statistical analysis highlighted a significant difference in Delta, Theta and Beta band evolution between detected and undetected seizures, in addition to variations in the magnitude of HR changes. Binomial logistic regression analysis confirmed that an increase in delta and theta band activity was associated with a decreased likelihood of seizure detection. This results suggest the possibility of distinct seizure spreading patterns between the two groups which may results in differential activation of the autonomic central network. Despite notable progress, limitations, particularly the absence of respiration recording, underscore areas for future exploration and refinement in closed-loop stimulation strategies for epilepsy management. This study constitutes the initial phase of a longitudinal investigation, which will subsequently involve reproducing these experiments in awake conditions with spontaneous recurrent seizures.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Analysis of the use of vagus nerve stimulator in the treatment of epilepsy

Refractory epilepsy poses a significant challenge in neurology due to approximately 30% of patients being resistant to conventional pharmacological treatments. This study investigates the efficacy and safety of vagus nerve stimulation (VNS) as a therapeutic alternative for these patients. The primary objective is to analyze the reduction in seizure frequency and improvements in the quality of life of patients treated with VNS. Additionally, the study aims to identify and categorize the side effects associated with the use of VNS. The methodology adopted included a qualitative bibliographic review covering renowned databases such as Scielo, Google Scholar, specialized scientific journals, academic repositories, and virtual libraries. Inclusion criteria considered studies that directly addressed the use of VNS in the treatment of epilepsy, while exclusion criteria eliminated duplicate and methodologically inadequate publications. Results indicate that VNS is effective in reducing seizures and improving quality of life, despite potential side effects. It is concluded that VNS is a viable and cost-effective therapeutic option for patients with refractory epilepsy, highlighting the need for future research to optimize stimulation parameters and minimize adverse effects.

Transcranial ultrasound with electrical stimulation of the cerebello-parietal nucleus on cerebral blood flow and limb function in patients with stroke.

To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

Efficacy of Deep Brain Stimulation for Treatment-Resistant Depression: Systematic Review and Meta-Analysis

BackgroundTreatment-resistant depression affects about 30% of individuals with major depressive disorder. Deep brain stimulation is an investigational intervention for treatment-resistant depression with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side-effect profiles. MethodsWe conducted a systematic PubMed review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomized controlled trials (n = 198) and 8 open-label trials (n = 77) were included spanning 2009 to 2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery–Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at the last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates. ResultsDeep brain stimulation achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement of around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects than randomized controlled trials. Long-term (12–60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available. ConclusionsDeep brain stimulation produces significant chronic improvement in symptoms of treatment-resistant depression. However, the limited sham-controlled data do not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.

Efficacy of sequential primary motor and prefrontal cortices intermittent Theta burst stimulation in persistent somatoform PAIN disorder (TAP-PAIN): A randomized sham-controlled pilot trial

Aim: There is a need to elucidate intermittent Theta burst stimulation (iTBS) as a novel treatment in persistent somatoform pain disorder (PSPD). Methods: Twenty patients were randomly allocated to active iTBS (n = 11) and sham iTBS (n = 9) and received 10 iTBS sessions, 2 sessions per day, sequentially to primary motor and dorsolateral prefrontal cortices for 5 days in a week. Each iTBS session comprised of 2 sec. per train of 10 bursts (3 pulses per burst at 50 Hz; total 30 pulses) and were given with a gap of 5 Hz, total of 20 trains, and 600 pulses. Visual Analogue Scale, Brief Pain Inventory and Global Pain Scale (GPS), Montgomery and Asberg Depression Rating Scale, Hamilton Anxiety Rating Scale - Anxiety, World Health Organization Quality-of-Life Scale-brief, and Pittsburgh Sleep Quality Index were applied at baseline, after last session, and at 2 weeks after last TBS session. Intention to treat analysis was conducted. Results: Both groups were comparable for baseline psychopathology scores including clinical variables like age (t = 0.865; P = 0.398), duration of illness (t = 1.600; P = 0.127), and motor threshold (t = 0.304; P = 0.765). On repeated measures ANOVA, a significant within-group time effect for VAS, BPI-Severity, BPI-Interference, BDI – II, MADRS, HAM-A, and WHOQOL- BREF was found for active and sham TBS groups, respectively. GPS scores had significant within-group (active) * time interaction (F = 11.651; P = .001; ηp2 = 0.538) and between-group * time interaction (F = 3.407; P = 0.044; ηp2 = 0.159). However, between-group * time effect interaction was lost after covariance (F = 1.726; P = 0.196; ηp2 = 0.110). Conclusion: No major adverse effects were reported. Our pilot trial concludes that safe therapeutic efficacy of iTBS in PSPD is inconclusive. Lower total number of sessions along with small sample size may limit the study findings.

Evaluating phasic transcutaneous vagus nerve stimulation (taVNS) with pupil dilation: the importance of stimulation intensity and sensory perception.

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation for frequent premature ventricular complexes: rationale and design of the TASC-V trial

BackgroundPremature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy.MethodsThe study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36).DiscussionThe TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice.Trial registrationClinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor- and Cygb-associated signaling pathways.

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease. Consequently, enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression. Nonetheless, non-pharmacological interventions aimed at inducing adult neurogenesis are currently limited. Although individual non-pharmacological interventions, such as aerobic exercise, acousto-optic stimulation, and olfactory stimulation, have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease, the therapeutic effect of a strategy that combines these interventions has not been fully explored. In this study, we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months. Amyloid deposition became evident at 4 months, while neurogenesis declined by 6 months, further deteriorating as the disease progressed. However, following a 4-week multifactor stimulation protocol, which encompassed treadmill running (46 min/d, 10 m/min, 6 days per week), 40 Hz acousto-optic stimulation (1 hour/day, 6 days/week), and olfactory stimulation (1 hour/day, 6 days/week), we found a significant increase in the number of newborn cells (5'-bromo-2'-deoxyuridine-positive cells), immature neurons (doublecortin-positive cells), newborn immature neurons (5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells), and newborn astrocytes (5'-bromo-2'-deoxyuridine-positive/ glial fibrillary acidic protein-positive cells). Additionally, the amyloid-beta load in the hippocampus decreased. These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice. Furthermore, cognitive abilities were improved, and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation, as evidenced by Morris water maze, novel object recognition, forced swimming test, and tail suspension test results. Notably, the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2 weeks after treatment cessation. At the molecular level, multifactor stimulation upregulated the expression of neuron-related proteins (NeuN, doublecortin, postsynaptic density protein-95, and synaptophysin), anti-apoptosis-related proteins (Bcl-2 and PARP), and an autophagy-associated protein (LC3B), while decreasing the expression of apoptosis-related proteins (BAX and caspase-9), in the hippocampus of amyloid precursor protein/presenilin 1 mice. These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways. Furthermore, serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis, oxidative damage, and cognition. Collectively, these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Efficacy and Safety of Vagus Nerve Stimulation in Lennox-Gastaut Syndrome: A Scoping Review.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant seizures, cognitive impairments, and abnormal electroencephalographic patterns. Vagus nerve stimulation (VNS) is a widely used neuromodulation therapy for LGS, but its effects on seizure outcomes, different seizure types, non-seizure outcomes, and adverse events in this population have not been comprehensively reviewed. To conduct a scoping review on the use of VNS in LGS, a literature search was performed in PubMed, OVID, Web of Science, and Embase from inception to 9 June 2024, using relevant keywords and without restrictions on study design. The search yielded forty eligible studies (twenty-four retrospective cohorts, fourteen prospective cohorts, and two registry analyses) comprising 1400 LGS patients treated with VNS. No randomized controlled trials were identified. Across studies, the median seizure reduction ranged from 20.6% to 65%, with 0% to 100% of patients achieving a ≥50% seizure reduction. No consistent preoperative biomarker of VNS responsiveness was identified in LGS. Although inconsistent among different studies, tonic, atonic, and tonic-clonic seizures responded best, while focal seizures responded worst. Improvements in seizure severity, alertness, and quality of life were reported in some studies, but cognitive and adaptive functioning generally remained unchanged. Adverse events were mostly mild and transient, including hoarseness, cough, and paresthesia. Device-related complications and infections were uncommon. In conclusion, further research is needed to better understand VNS's position in the evolving LGS treatment landscape and its cost effectiveness.

The efficacy of transcranial random noise stimulation in treating tinnitus: a systematic review.

This review aims to examine the effects of transcranial random noise stimulation (tRNS) on tinnitus and to determine the optimal treatment parameters, if possible. A comprehensive search, including MEDLINE, PubMed, EMBASE, CINAHL, SCOPUS, and PEDro, was conducted to determine experiments studying the effects of tRNS on tinnitus from inception to March 1, 2024. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the quality of the included studies. Seven studies met the eligibility criteria. A total of 616 patients with non-pulsatile tinnitus (mean age 50.93 years; 66% males) were included in this review. The included studies ranged from 3 to 8 out of 10 (median = 7) on the PEDro scale. The results showed that tRNS is an effective intervention in reducing tinnitus symptoms. The evidence for the effects of tRNS on people with chronic non-pulsatile tinnitus is promising. Administering tRNS with an intensity of 1-2mA, high-frequency (101-650Hz), using a 35cm² electrode size over the auditory cortex and DLPFC, for 20min with eight sessions may demonstrate the desired tRNS effects. The tRNS stimulation should be contralateral for unilateral tinnitus and bilaterally for bilateral tinnitus. Combining tRNS with other concurrent interventions may show superior effects in reducing tinnitus compared to tRNS alone. Further high-quality studies with larger sample sizes are strongly needed.

Feasibility and Safety of an Eight-Week Exercise Program with the Additional Peripheral Magnetic Stimulation of the Abdominal Muscles.

Peripheral magnetic stimulation has recently been introduced as a non-invasive but effective physical agent to improve muscle strength and everyday function. The aim of this study was to evaluate the feasibility and safety of an exercise program focusing on the abdominal muscles in combination with the peripheral magnetic stimulation of the abdominal muscles. Male and female overweight and obese adults (n = 19) participated in an eight-week exercise program with the additional peripheral magnetic stimulation of the abdominal muscles. Outcome measures included changes in abdominal subcutaneous fat thickness, trunk muscle strength, body composition, and self-reported body satisfaction. Subcutaneous fat thickness was significantly reduced after the intervention (p < 0.01-p < 0.001). Trunk flexion and left side flexion strength increased significantly after the intervention, although no significant changes were observed for trunk extension (p = 0.07) and right side flexion strength (p = 0.13). The body satisfaction self-assessment score significantly increased (p < 0.01), while body mass, body mass index, and fat mass significantly decreased after the intervention (p < 0.05). Our findings suggest that an exercise program with the additional peripheral magnetic stimulation is feasible and safe for overweight and obese participants. These results support the use of peripheral magnetic stimulation as a safe adjunct to the voluntary abdominal muscle contraction. Future studies are needed to evaluate the efficacy of the additional peripheral magnetic stimulation of the abdominal muscles compared to the voluntary contraction of the abdominal muscles alone.

Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia

ObjectiveThis study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. MethodsSixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. ResultsOf the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). ConclusionsTDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SignificanceThis study provides a novel perspective for the clinical treatment of patients with TD.

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.

Evaluating the Efficacy of Vagus Nerve Stimulation across 'Minor' and 'Major' Seizure Types: A Retrospective Analysis of Clinical Outcomes in Pharmacoresistant Epilepsy.

Background: Evaluating the differential impact of vagus nerve stimulation (VNS) therapy across various seizure types, our study explores its efficacy specifically in patients with categorized minor and major seizures. Methods: We conducted a retrospective cohort study involving 76 patients with pharmacoresistant epilepsy treated at the University Emergency Hospital of Bucharest between 2021 and 2024. Seizures were classified as 'minor' (including focal-aware and non-motor/absence seizures) and 'major' (including focal to bilateral tonic-clonic and generalized motor seizures), based on modified International League Against Epilepsy (ILAE) criteria. This classification allowed us to assess the response to VNS therapy, defined by a 50% or greater reduction in seizure frequency at the 12-month follow-up. Results: Our findings reveal that major seizures respond more favorably to VNS therapy, significantly reducing both frequency and intensity. In contrast, minor seizures showed a less pronounced response in frequency reduction but noted improvements in neurocognitive functions, suggesting a nuanced benefit of VNS in these cases. Conclusion: The study underscores the importance of seizure type in determining the efficacy of VNS therapy, advocating for personalized treatment approaches based on seizure classification. This approach could potentially enhance clinical outcomes by tailoring VNS settings to specific seizure types, improving overall management strategies in pharmacoresistant epilepsy.

Chronic Electro-Acoustic Stimulation May Interfere With Electric Threshold Recovery After Cochlear Implantation in the Aged Guinea Pig.

Electro-acoustic stimulation (EAS) combines electric stimulation via a cochlear implant (CI) with residual low-frequency acoustic hearing, with benefits for music appreciation and speech perception in noise. However, many EAS CI users lose residual acoustic hearing, reducing this benefit. The main objectives of this study were to determine whether chronic EAS leads to more hearing loss compared with CI surgery alone in an aged guinea pig model, and to assess the relationship of any hearing loss to histology measures. Conversely, it is also important to understand factors impacting efficacy of electric stimulation. If one contributor to CI-induced hearing loss is damage to the auditory nerve, both acoustic and electric thresholds will be affected. Excitotoxicity from EAS may also affect electric thresholds, while electric stimulation is osteogenic and may increase electrode impedances. Hence, secondary objectives were to assess how electric thresholds are related to the amount of residual hearing loss after CI surgery, and how EAS affects electric thresholds and impedances over time. Two groups of guinea pigs, aged 9 to 21 months, were implanted with a CI in the left ear. Preoperatively, the animals had a range of hearing losses, as expected for an aged cohort. At 4 weeks after surgery, the EAS group (n = 5) received chronic EAS for 8 hours a day, 5 days a week, for 20 weeks via a tether system that allowed for free movement during stimulation. The nonstimulated group (NS; n = 6) received no EAS over the same timeframe. Auditory brainstem responses (ABRs) and electrically evoked ABRs (EABRs) were recorded at 3 to 4 week intervals to assess changes in acoustic and electric thresholds over time. At 24 weeks after surgery, cochlear tissue was harvested for histological evaluation, only analyzing animals without electrode extrusions (n = 4 per ear). Cochlear implantation led to an immediate worsening of ABR thresholds peaking between 3 and 5 weeks after surgery and then recovering and stabilizing by 5 and 8 weeks. Significantly greater ABR threshold shifts were seen in the implanted ears compared with contralateral, non-implanted control ears after surgery. After EAS and termination, no significant additional ABR threshold shifts were seen in the EAS group compared with the NS group. A surprising finding was that NS animals had significantly greater recovery in EABR thresholds over time, with decreases (improvements) of -51.8 ± 33.0 and -39.0 ± 37.3 c.u. at 12 and 24 weeks, respectively, compared with EAS animals with EABR threshold increases (worsening) of +1.0 ± 25.6 and 12.8 ± 44.3 c.u. at 12 and 24 weeks. Impedance changes over time did not differ significantly between groups. After exclusion of cases with electrode extrusion or significant trauma, no significant correlations were seen between ABR and EABR thresholds, or between ABR thresholds with histology measures of inner/outer hair cell counts, synaptic ribbon counts, stria vascularis capillary diameters, or spiral ganglion cell density. The findings do not indicate that EAS significantly disrupts acoustic hearing, although the small sample size limits this interpretation. No evidence of associations between hair cell, synaptic ribbon, spiral ganglion cell, or stria vascularis with hearing loss after cochlear implantation was seen when surgical trauma is minimized. In cases of major trauma, both acoustic thresholds and electric thresholds were elevated, which may explain why CI-only outcomes are often better when trauma and hearing loss are minimized. Surprisingly, chronic EAS (or electric stimulation alone) may negatively impact electric thresholds, possibly by prevention of recovery of the auditory nerve after CI surgery. More research is needed to confirm the potentially negative impact of chronic EAS on electric threshold recovery.

Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review.

The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP). We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation. A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect. NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.