Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 7 appraisals
Journal of affective disorders
Transcranial focused ultrasound for emotion regulation: A systematic review and quantitative summary of human studies.
BACKGROUND: Emotion regulation is a core transdiagnostic process in mood, anxiety, and stress-related disorders. While existing non-invasive brain stimulation approaches, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can modulate affective networks, their clinical use is limited by restricted spatial precision and depth penetration. Transcranial focused ultrasound stimulation (tFUS) offers submillimeter focality and access to both cortical and deep subcortical structures, making it a promising tool for affective neuromodulation. METHODS: We systematically searched PubMed, Embase, and PsycINFO for human studies using tFUS to modulate emotion regulation, affective processing, or related symptoms. Eligible studies included randomized controlled trials (RCTs), open-label, and within-subject designs. Data on stimulation parameters, target regions, outcomes, and safety were extracted. Effect sizes were calculated and pooled using a random-effects model, with subgroup analyses by clinical domain. RESULTS: Eleven studies met inclusion criteria, targeting the amygdala (n = 5), prefrontal cortex (n = 5), or subcallosal cingulate cortex (n = 1), with protocols varying in frequency (250-650 kHz), duty cycle (0.5-70%), and number of sessions (1-25). Across six studies reporting behavioral symptom outcomes, the pooled effect was moderate-to-large (Hedges' g = 0.88, 95% CI [0.47, 1.29]), with larger effects in depression-related measures (g = 1.31) than in anxiety-related measures (g = 0.67). Imaging outcomes were reported in a smaller subset of studies and were not included in the pooled estimates. No serious adverse events were reported. CONCLUSIONS: tFUS is a safe and well-tolerated intervention capable of engaging deep affective circuits; however, quantitative estimates remain preliminary given the small and heterogeneous evidence base. Future large-scale, harmonized, and mechanistically informed trials are warranted to refine protocols, establish durability, and optimize translation into clinical practice.
15 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Combined transcranial direct current stimulation and mirror therapy for upper limb rehabilitation in patients with stroke: a systematic review and meta-analysis
Upper limb impairment is among the common consequences of stroke. Combining transcranial direct current stimulation (tDCS) and mirror therapy (MT) have recently been used to improve neural plasticity and functional recovery. This review aims to evaluate the effects of combined tDCS and MT on upper limb function in patients with stroke. "PubMed, Scopus, Web of Science, CINAHL, PEDro, and EMBASE" were searched from their inception to March 2026. Randomized controlled trials investigating the combination of tDCS and MT in patients with stroke and assessing upper limb function were included. The quality and the certainty of evidence were evaluated. Seven studies (454 participants) met the eligibility criteria. Significant improvements were demonstrated in upper limb motor function (SMD = 0.73, 95% CI 0.34 to 1.12, p = 0.0002), activities of daily living (SMD = 0.84, 95% CI 0.46 to 1.22, p < 0.0001), and neurophysiological outcomes reflecting corticospinal conduction efficiency, assessed using central motor conduction time (CMCT) (SMD = -1.26, 95% CI -1.60 to -0.92, p < 0.0001). Subgroup analysis demonstrated greater effects in subacute stroke (SMD = 1.03, 95% CI 0.73 to 1.33). Other outcomes reported improvements in hand function and grip strength. Preliminary evidence suggests that combining tDCS and MT may improve upper limb motor and functional outcomes after stroke; however, these findings should be interpreted with caution due to heterogeneity and the limited data. Further studies are strongly needed.
11 July 2026
Read appraisal →Brain topography
Local Field Potential Recordings Using Deep Brain Stimulation: A Practical Workflow and Open-Source Signal Processing Pipeline
Deep brain stimulation (DBS) systems with electrophysiological recording capabilities offer a unique opportunity to chronically record local field potentials (LFP) from implanted electrodes, enabling real-time monitoring of subcortical neural dynamics and the development of adaptive neuromodulation strategies. However, translating raw LFP into clinically relevant biomarkers remains challenging due to numerous technical considerations. To address this, we share both a practical guide for conducting LFP experiments and BrainWave-DBS, an open-source pipeline that implements the workflow and supports analysis of patient-derived LFP data. The pipeline covers data import, preprocessing, spectral analysis, and visualization, offering a reproducible framework for LFP analysis. Furthermore, we demonstrate the functionality of the pipeline using a representative Parkinson's disease dataset and highlight key technical insights gained through this work. By improving access to neural signal acquisition and analysis, our goal is to foster broader adoption of this technology, which could advance closed-loop neuromodulation of deep brain structures.
29 June 2026
Read appraisal →Psychological medicine
Sorting the mind: cognitive enhancement through transcutaneous auricular vagus nerve stimulation: a systematic review and meta-analysis
Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive technique engaging vagal afferents that may enhance cognition, but results vary across domains and samples. Following PRISMA, seven databases (inception-October 2025) plus registries and gray literature were searched. Random-effects meta-analyses (REML; Hedges' g) were complemented by Bayesian hierarchical models and sensitivity analyses. Fifty-three studies were included; 30 contributed quantitative data (>1,500 participants). taVNS was associated with improved cognitive performance overall (g = 0.41, 95% CI: 0.30-0.53; I2 = 51.4%). Effects were moderate for executive functions (g = 0.46, 95% CI: 0.27-0.65; I2 = 9.5%) and cognitive flexibility/learning (g = 0.53, 95% CI: 0.32-0.75; I2 = 52.9%), and small for working memory/attention (g = 0.19, 95% CI: 0.04-0.33; I2 = 14.9%). Social cognition/emotion regulation showed larger but imprecise effects (k = 3; g = 0.80, 95% CI: 0.07-1.52; I2 = 82.1%). Clinical samples benefited similarly (k = 7; g = 0.55, 95% CI: 0.31-0.79; I2 = 29.5%), with no difference from healthy cohorts (β = -0.001, p = .994). High-intensity protocols (>1.0 mA) yielded larger effects; mode, duration, and site were not moderators. Bayesian models supported effects (P [μ > 0] ≥ 0.93). taVNS is associated with statistically significant improvements in cognitive performance, strongest for executive control and adaptive learning. We propose a Vagal Neurocognitive Integration Model linking LC-NE arousal modulation to prefrontal control. Future diagnosis-specific, adequately powered trials with multimodal neuroimaging should refine mechanisms and dose-response.
25 June 2026
Read appraisal →Journal of affective disorders
Right orbitofrontal cortex rTMS targets anxiety, not depressive, symptoms in first-episode schizophrenia.
BACKGROUND: Anxiety is highly prevalent and undertreated in first-episode schizophrenia(FES), but repetitive transcranial magnetic stimulation(rTMS) data for this comorbidity are scarce. The orbitofrontal cortex(OFC) is a key anxiety-regulating node, supporting its potential as a target. This study aimed to explore 1-Hz right OFC-rTMS's symptom-specific effects on FES mood. METHODS: This is a secondary analysis of a randomized controlled trial. Participants were drug-naive FES patients randomized to the active rTMS group(n = 51) or sham group(n = 45). All completed 20 intervention sessions, 20 sessions of active OFC-rTMS or sham, with 4-week follow-up, initiating oral olanzapine(10-20 mg/day) concurrently with the first rTMS session. Mood symptoms were assessed using the 24-item Hamilton Depression Rating Scale(HAMD) and the 14-item Hamilton Anxiety Rating Scale(HAMA). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS). The main outcome was the changes in HAMD and HAMA scores from baseline to 2 weeks and 4 weeks. RESULTS: The active group showed greater PANSS total(t = -3.260, p = 0.002; Cohen's d = 0.672) and subscale improvements vs. the sham group. Repeated-measures ANOVA(controlling for covariates) revealed significant Time×Group interactions for HAMA total(F = 4.698, p = 0.010; partial η2 = 0.059) and psychic anxiety(F = 5.735, p = 0.004; partial η2 = 0.072), but not somatic anxiety. For HAMD, only anxiety/somatization(F = 8.397, p = 0.031; partial η2 = 0.099) and cognitive impairment(F = 6.240, p = 0.002; partial η2 = 0.076) showed interactions, with no specific effects on overall depressive symptoms. In the sham group, HAMD anxiety/somatization correlated with all PANSS subscales(r = 0.311-0.477, p < 0.05), but this correlation was absent in the active group(all p > 0.05). CONCLUSIONS: Right OFC-rTMS improves FES anxiety (not depression), supporting it as a targeted non-pharmacological option.
17 May 2026
Read appraisal →PloS one
A secondary head-to-head comparison of low-intensity focused ultrasound and repetitive transcranial magnetic stimulation for motor recovery after stroke
BACKGROUND: Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with high spatial precision and the ability to reach deeper brain regions, offering potential advantages for post-stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive brain stimulation technique that modulates cortical excitability to promote neuroplasticity. However, direct head-to-head comparisons between these two modalities for post-stroke motor recovery remain limited. OBJECTIVE: To perform a secondary head-to-head comparison of LIFU and repetitive transcranial magnetic stimulation (rTMS) for motor recovery after stroke, based on a prospectively registered randomized controlled trial. METHODS: This secondary analysis included patients with subacute stroke who received two weeks of standard rehabilitation combined with either LIFU (n = 25) or rTMS (n = 25) targeting the ipsilesional primary motor cortex. LIFU parameters: 0.5 MHz, spatial-peak pulse-average intensity (ISPPA) 10.2 W/cm² (free-field), pulse duration 0.2 ms, duty cycle 20%, 20 minutes per session, five days per week for two weeks (10 sessions total). rTMS parameters: 10 Hz, 80% resting motor threshold, 1,000 pulses per session (20 trains of 5 seconds), 20 minutes per session, five days per week for two weeks (10 sessions total). Motor outcomes were assessed using the Fugl-Meyer Assessment (FMA; upper and lower extremities), Modified Barthel Index (MBI), and Brunnstrom stages. Resting-state functional near-infrared spectroscopy (fNIRS) was used to evaluate cortical activity and functional connectivity before and after the intervention. Primary analyses were conducted in the intention-to-treat (ITT) population (n = 50), with completer analyses (n = 43) performed as sensitivity analyses. RESULTS: Both groups showed significant within-group improvements in FMA and MBI after the intervention (all p < 0.001), and changes in Brunnstrom stages were also uniformly significant. No statistically significant between-group differences were observed in post-intervention FMA, MBI, or Brunnstrom stages (all p > 0.05), and completer analyses yielded consistent between-group conclusions. In contrast, change-from-baseline analyses demonstrated greater improvements in FMA scores in the LIFU group compared with the rTMS group (ΔFMA upper limb: median 7 [IQR 3-10.5] vs. 2 [1-3], p = 0.001; lower limb: 3 [1-4.5] vs. 1 [0-1.5], p < 0.001). Exploratory fNIRS analyses revealed modality-specific patterns: prefrontal fractional amplitude of low-frequency fluctuations (fALFF) increased significantly in the LIFU group (p = 0.002) but not in the rTMS group, while functional connectivity changes did not remain significant after correction for multiple comparisons. CONCLUSION: LIFU and rTMS were associated with comparable short-term motor outcomes in subacute stroke. Differences observed in change-from-baseline motor improvements and exploratory neuroimaging measures suggest potential divergence in recovery dynamics and cortical modulation, warranting further investigation in larger, longitudinal studies. TRIAL REGISTRATION: This study was derived from a prospectively registered, three-arm randomized controlled trial in the Chinese Clinical Trial Registry (ChiCTR2500114687). The present manuscript reports a secondary head-to-head comparison between the two neuromodulation intervention arms.
27 Apr 2026
Read appraisal →PloS one
A pilot randomized controlled trial of neuromodulation-augmented balance training in people with multiple sclerosis: STIM-Balance Protocol
BACKGROUND: Impairments in balance control and falls are common problems for people with multiple sclerosis (PwMS), resulting in mobility limitations and reduced participation. Non-invasive neuromodulation techniques such as functional electrical stimulation (FES) and transcutaneous spinal stimulation (TSS) have revealed promising results in improving motor functions in other neurological populations; however, their effects during task-specific balance training have not been investigated in PwMS. OBJECTIVE: To evaluate the feasibility, acceptability, safety, and preliminary clinical efficacy of neuromodulation-augmented balance training programs on balance, mobility, and neuroplasticity in PwMS (ClinicalTrials.gov Identifier: NCT07174973). METHODS: Twenty-four ambulatory PwMS will be randomly assigned into three groups: (1) visual feedback balance training (VFBT) with sham stimulation, (2) VFBT with active (closed-loop) FES for the ankle muscles and sham TSS, and (3) VFBT with active FES and active (open-loop sub-motor-threshold) TSS at the lumbosacral enlargement. Participants in each group will complete 12 training sessions over six weeks. Feasibility, safety, and acceptability will be assessed through recruitment and adherence metrics, adverse-event monitoring, and semi-structured interviews guided by the Technology Acceptance Model questionnaire-2. Performance-based measures of balance, mobility, and walking speed, as well as patient-reported outcomes of balance confidence, walking ability, and fear of falling will be recorded to assess the preliminary efficacy. Modulation in neural pathways excitability will be quantified by recording motor evoked potentials and spinal motor evoked potentials. CONCLUSION: Findings will help to determine whether neuromodulation-augmented balance training is feasible, safe, and acceptable for PwMS and will guide the design of a future fully powered RCT.
17 Apr 2026
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