Sleep-wake disorders are common in numerous neurological and psychiatric conditions, yet current treatments often yield incomplete results. Given the subcortical nature of sleep regulation, intracranial stimulation, and particularly deep brain stimulation (DBS), emerges as a promising therapeutic strategy. This narrative review synthesizes preclinical and clinical evidence regarding the effects of DBS and DBS-like invasive stimulation across multiple brain regions implicated in sleep-wake (SW) control. Additionally, stimulation targeting non-SW related targets has also shown incidental effects on sleep and wakefulness. Evidence reveals target- and frequency-dependent effects on sleep architecture and arousal, with notable translational success in Parkinson's Disease and Obsessive-Compulsive Disorder. The discussion addresses three central questions: (1) Which brain areas modulate sleep and wakefulness when stimulated? (2) How do stimulation parameters influence these outcomes? (3) What are the challenges and limitations in moving toward sleep-wake-primary indications? Despite encouraging results, variability in reported measures and outcomes underscores the need for objective, standardized sleep measures (polysomnography) and advanced targeting. Overall, this review may assist clinicians in optimizing DBS parameters in patients experiencing sleep-wake disturbances and underscores the broader potential of invasive neuromodulation both as a therapeutic strategy and as a tool to better characterize sleep and wakefulness dynamics.
Deep Brain Stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD), yet registry-based data from developing countries remain limited. This study reports the establishment and feasibility of the Iranian Deep Brain Stimulation Registry for Parkinson's Disease (IDBSR-PD). We conducted a single-center feasibility study at the Research Center for Neuromodulation and Pain, including all PD patients undergoing DBS implantation since 2014. Primary feasibility outcomes included patient enrollment coverage, follow-up adherence, data completeness, multidisciplinary implementation, and the sustainability of technical infrastructure. Secondary outcomes included descriptive patient characteristics. Only descriptive statistics were performed; no hypothesis testing or longitudinal outcome analyses were conducted. A total of 208 patients were enrolled (65.4% male; mean age 58.4 ± 10.2 years). Enrollment increased progressively over time, peaking in 2024 (n = 41). Patients were referred from multiple provinces across Iran. Data validation mechanisms and regular surveillance ensured acceptable data completeness. The IDBSR-PD demonstrates the feasibility and sustainability of a web-based DBS registry in a developing country. These findings confirm the viability of structured data collection and provide a foundation for future multicenter and longitudinal outcome research.
Goal: Existing beta burst detection algorithms for closed-loop deep brain stimulation (DBS) are computationally complex, limiting their use in implantable devices. We aimed to develop an improved beta burst extraction algorithm for chip-based DBS devices with real-time model updating. Methods: Building on an established beta burst detection method, we proposed a sliced mechanism for peak frequency finding and modified burst extraction for information sharing with real-time model updating. Results: Testing on rat electrocorticographic (ECoG) recordings showed that the proposed algorithm maintains a strong correlation ( 0.89 0.06) with the conventional method, with a 53.3 reduction in computational complexity for peak frequency finding. Conclusions: Integrating this improved beta burst detection into chip-based DBS devices represents a key algorithmic advancement toward adaptive neuromodulation therapies. The strong correlation and reduced complexity validate our proposal for real-time neural biomarker tracking, facilitating hardware and chip implementation, and advancing the development of implantable systems.
Deep brain stimulation (DBS) outcomes depend on accurate lead placement. Robot-assisted DBS (RA-DBS) has been increasingly adopted, yet its advantages over conventional non-robotic frame-based DBS (NRA-DBS) regarding targeting accuracy, operative efficiency, and clinical outcomes remain debated.To compare RA-DBS versus NRA-DBS for targeting accuracy and clinical outcomes in patients undergoing DBS for movement disorders.This meta-analysis and systematic review was registered in PROSPERO (CRD420261336001) and adhered to PRISMA. Patients with mobility disorders treated with RA-DBS versus frame-based NRA-DBS were included in comparative studies (RCTs and prospective/retrospective cohorts). Targeting accuracy measures (such as target point error, vector error, and radial error) and extreme targeting outliers were the main results. Operative time measurements, perioperative problems (such as cerebral bleeding), and motor improvement (UPDRS-III) were secondary outcomes. Fixed-effects or random-effects models based on heterogeneity were used to compute pooled odds ratios (OR) and weighted mean differences (MD) with 95% confidence intervals (CI). Nine high-quality comparative studies encompassing 495 patients (227 RA-DBS vs. 268 NRA-DBS) were synthesized. RA-DBS significantly minimized target point error (MD = -0.31 mm, 95% CI: -0.61 to -0.01; P = 0.04) and significantly reduced the incidence of clinically significant targeting outliers (OR = 0.15, 95% CI: 0.04 to 0.51; P = 0.002). Comprehensive three-dimensional vector error was marginally lower in the RA-DBS cohort (MD = -0.70 mm; P = 0.05), whereas two-dimensional radial error and total operating room time, surgical duration, anesthesia time, perioperative complications, and 12-month UPDRS-III motor improvements were statistically equivalent between groups. Subgroup analyses revealed that the spatial precision advantage of RA-DBS was geographically robust across East Asian and Western cohorts, whereas chronological efficiency was heavily dependent on the specific robotic platform used.Compared with conventional frame-based stereotaxy, robot-assisted DBS significantly enhances target point precision and reduces electrode deviations. However, these technical accuracy advantages do not translate into overall clinical superiority, as both approaches yield comparable operative efficiency, perioperative safety, and mid-term motor symptom relief.
Children with severe self-injurious behaviour (SIB) are at risk of permanent injury and lack effective treatment options. Neuromodulation of the nucleus accumbens (NAc), a key node in reward and behavioural regulation circuits, may directly modulate the drivers of SIB. We report long-term outcomes from a first-in-human, single-centre trial of deep brain stimulation (DBS) targeting the NAc in children and adolescents with profound autism and treatment-refractory SIB (NCT03982888). Six participants (ages 7-14 years; mean 11.7) underwent bilateral implantation and were followed prospectively for at least 24 months (mean 32.5 months, range 25.8-56.0). One serious adverse event occurred: a device-related infection requiring hardware explantation, followed by relapse to baseline levels of self-injury. Subsequent re-implantation in this participant yielded rapid improvement in SIB, providing single-subject, causal withdrawal-rechallenge evidence of treatment-specific benefit. Across the cohort, NAc-DBS produced sustained reductions in SIB frequency and severity, repetitive and obsessive-compulsive behaviours, and clinically meaningful improvements in quality of life. The durability of these effects over multi-year follow-up suggests that circuit-targeted neuromodulation may modify the developmental course of severe behavioural pathology. These findings provide the first long-term evidence that modulation of reward circuitry can durably alter maladaptive behaviour in childhood neurodevelopmental disorders.
Clinically used magnetic resonance imaging (MRI) modalities field strengths (1.5T and 3T) are not optimal for minimizing either geometric distortion nor maximizing image quality, respectively, when imaging patients with DBS. Lower and higher field strengths can be used to overcome these limitations by improving imaging resolution and reducing geometric distortion. Our aim is to assess the safety and feasibility of DBS at non-conventional (not 1.5T, 3T) MRI to explore more effective options for scanning patients with DBS. We performed a search of preclinical and human studies investigating the safety of non-conventionally used MRI field strengths (i.e., not 1.5T or 3T) for deep brain stimulation (DBS). Relevant articles were retrieved from OVID, PubMed, and Web of Science from database inception to August 25, 2025. Twelve studies were included. Seven studies assessed safety of DBS at ultra-high-field (UHF) MRI. Five studies assessed safety of DBS at low-field MRI. No human studies were found. For in-silico and in-vitro studies, measures of radiofrequency energy deposition and heating of the hardware were recorded whereas for in-vivo studies, clinical and histological assessments were retrieved. For in-vitro and in-silico studies, heating of DBS systems were within clinically acceptable parameters for realistic configurations and intended use sequences of DBS placements in non-conventional UHF (> 3 T) and low-field MRI (< 1.5T). For in-vivo studies, no significant histological damages were observed at UHF MRI compared to 3T and 1.5T. Our systematic review is limited by the lack of human studies and variations in scanning sequences across studies. Our findings comprising of pre-clinical studies provide early data on the safety of UHF and low-field MRI for DBS. At this stage, studies do not support scanning DBS patients at these field strengths, but provide a framework for developing human studies examining the safety of DBS in non-conventional MRI.
Although auditory sensory stimulation has been widely used in clinical occupational therapy practice for DOC, there is significant heterogeneity in specific implementation protocols. However, none of these studies have focused specifically on exploring the familiar voice of subject's own name (FV SON) vs. unfamiliar voice of subject's own name (UFV SON) calling. Functional near-infrared spectroscopy (fNIRS) has shown great potential in the clinical assessment of DOC, as it features both high portability and relatively high spatial resolution. This study used fNIRS to investigate the real-time cortical activation elicited by auditory sensory stimulation through FV SON and UFV SON in patients with DOC, aiming to provide meaningful guidance for clinical occupational therapy and treatment evaluation. A total of 64 participants with DOC were recruited for this study. FNIRS was used to detected blood oxygen signals during FV SON and UFV SON in the subjects. Statistical analyses were performed for intra-group differences and the relationships between fNIRS metrics and the scores of the CRS-R. Participants with DOC under UFV SON stimulation exhibited deactivation in the Left Dorsolateral Pre-frontal Cortex (DLPFC-L). However, compared with the rest state (RS), participants with DOC under FV SON stimulation did not show deactivation in the DLPFC-L. Compared with the UFV SON stimulation, the peak value of participants with DOC under FV SON stimulation was greater in the DLPFC-L. However, compared with the FV SON stimulation, the peak value of participants with DOC under UFV SON stimulation was greater for the TC-L. Compared with the UFV SON stimulation, the initial slope of participants with DOC under FV SON stimulation was greater for PreM & SMC-L. Under FV SON stimulation, the peak values of the DLPFC-L and TC-L were positively correlated with the CRS-R VFS score. Under UFV SON stimulation, the peak value of the TC-L was positively correlated with the CRS-R total score, CRS-R VFS score and CRS-R AS score; the peak value of the PMC-L was positively correlated with the CRS-R total score, CRS-R AFC score and CRS-R VFS score; and the peak value of the Broca-L was positively correlated with the CRS-R total score, CRS-R VFS score and CRS-R AS score. Under UFV SON stimulation, the initial slope of the DLPFC-L was positively correlated with the CRS-R AFC score. In conclusion, DOC patients show distinct cortical activation patterns under familiar vs. unfamiliar SON calling stimulation. This study is helpful for guiding auditory stimulation strategies or personalized rehabilitation in DOC. These conclusions warrant further validation in future larger, multicenter studies, multimodal neuroimaging, studies, and intervention-based studies. [ChiCTR2300074202].
Sophisticated hand movements are essential for daily activities, but central neurological impairments often compromise them. Since full recovery through conventional physiotherapy is rare, assistance is crucial. While neural implants show promise, clinical use remains distant, urging immediate assistive alternatives. Current exoskeletons and neurostimulation garments lack sufficient motor support and sensory feedback, limiting dexterity. We developed a neurorobotic system combining portable exoskeletons with targeted neurostimulation via custom-made e-sleeve and tested it in 14 individuals with central neural injuries. We provide evidence of restored finger mobility and tactile perception, even in patients with clinically complete sensory loss, by recruiting residual peripheral pathways. Eight participants completed functional assessments, in which they exploited neurostimulation to improve grasp precision and enhance strength. This enabled manipulation of fragile and cumbersome objects, essential for everyday activities. Personalized assistive technologies have clinical potential to promote independence and support the reintegration of people with neurological impairments into society.
Deep brain stimulation (DBS) targeting the ventral internal capsule/ventral striatum (VCVS) is an effective treatment for several psychiatric disorders, but clinical responses often vary amongst patients likely due to an incomplete mechanistic understanding of the brain pathways mediating response. VCVS DBS can improve cognitive control, a core deficit in multiple psychiatric disorders. Here, we investigated which prefrontal cortical pathway(s) in the internal capsule are associated with improving cognitive control during VCVS DBS. Four participants with bilateral VCVS DBS completed the Multi-Source Interference Task (MSIT) under 27 stimulation settings varying by side (left/right lead), electrode, amplitude, and frequency. Each condition included 100 trials and response time (RT) assessed task performance. Personalized pathway activation models quantified axonal recruitment across 11 segmented prefrontal cortical fiber bundles per brain hemisphere. Associations between pathway activation and task RT were analyzed to identify circuits linked to improved cognitive control performance. Right-sided VCVS stimulation produced greater improvements in cognitive control (reductions in MSIT RT) than left-sided stimulation. Activation of right dorsal prefrontal cortical pathways connected to the dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) most strongly predicted faster MSIT RTs, whereas no left-sided pathways were associated with performance changes. These findings suggest that the effects of VCVS DBS on cognitive control are primarily mediated by right dorsal prefrontal cortical axons projecting from the dlPFC and dmPFC. Targeting these pathways may improve stimulation strategies and outcomes for psychiatric disorders characterized by impaired cognitive control.
As an anatomical extension of the central nervous system (CNS), the eye harbors rich neural and immune interfaces with the brain. However, the integrated immunological and neurological nexus between the eye and CNS remains unexplored. Here, we identify the existence of an eye-brain neuroimmune axis by analyzing immune and neuronal responses to eye-brain electrical stimulation (ES). ES-assisted intravitreal immunization (IVT) prolonged survival in a murine glioblastoma model, with 33.3% of mice surviving to day 50. Mechanistically, the eye-brain neuroimmune axis serves two pivotal roles: (1) Immune activation: ES accelerates the rapid drainage of intravitreally delivered antigens to deep cervical lymph nodes (dCLNs), bypassing the BBB and triggering robust CNS-specific immune responses; (2) Disruption of pathological neuron connectivity: the expression of synaptogenic factors and neuronal excitability can also be mediated under ES treatments. These results uncover an unexplored brain neuroimmune connection, offer new insights into the pathophysiology of eye-brain diseases and suggest promising avenues for precise diagnostic and therapeutic strategies targeting both ocular and CNS disorders.
Magnetic continuous theta burst stimulation (cTBS) is known to suppress human motor cortical excitability. Whether transcranial ultrasound stimulation (TUS) delivered in a continuous theta burst pattern (ctbTUS) produces similar inhibitory effects and whether co-applying ctbTUS with cTBS enhances these effects remains unclear. Four stimulation conditions: ctbTUS + sham cTBS (ctbTUS), sham ctbTUS + cTBS (cTBS), sham ctbTUS + sham cTBS (sham), and ctbTUS + cTBS (cosTBS) were applied. Fifteen participants underwent neurophysiological testing with motor-evoked potentials (MEPs) recorded at 0, 10, 20, and 60 min post-stimulation, normalized to pre-intervention baselines. Additionally, 18 participants underwent resting-state functional MRI (rsfMRI) to assess functional connectivity (FC) between the hand representation of the motor cortex (M1) and other brain regions. Simulated skull density, transducer-skull space, and online-inhibition characteristics were evaluated as modulatory factors. ctbTUS induced inhibitory after-effects measured by MEP amplitude lasting up to 60 min (p = 0.001). However, cosTBS reduced this inhibition, although immediate MEP suppression remained (p = 0.024). rsfMRI revealed reduced FC between M1 and bilateral pre/post-central gyri and increased cerebellar FC after ctbTUS, but such after-stimulation patterns were absent after cosTBS. Higher pseudo-computed-tomography-derived skull density was associated with more negative ΔFC (or FC suppression, β = -0.844, p = 0.004). Participants with online inhibition showed greater offline MEP suppression (p = 0.004). ctbTUS induced inhibitory after-effects lasting up to 60 min but cosTBS decreased this suppression, likely via calcium-dependent plasticity or homeostatic plasticity effects. Skull density, and individual sensitivity to TUS are critical factors influencing TUS efficacy.
Animals sense food quantity and quality to regulate feeding behaviors. Enteroendocrine cells (EECs) in the gut epithelium detect luminal distension and nutrients, signaling this information to the brain via vagal sensory neurons. However, how mechanosensory and chemosensory signals are dynamically encoded by gut-brain circuits remains unclear, particularly during early development. Using larval zebrafish, we developed a feeding assay with particles releasing specific nutrients after consumption, demonstrating that EECs regulate nutrient-specific feeding days after gut formation. To determine how post-ingestive signals are encoded along gut-brain circuitry, we developed a microgavage method enabling simultaneous gut stimulation and two-photon imaging. Gut distension alone drove widespread activation and suppression in vagal and dorsal hindbrain neurons. Although nutrient-evoked responses shared temporal features with distension, allyl isothiocyanate elicited slower-onset dynamics. These findings reveal that fast gut-to-brain communication emerges early in life, with distension and aversive chemical cues encoded through distinct temporal dynamics in developing interoceptive circuits.
Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), is considered a safe method to modulate cortical activity and endogenous brain oscillations. Given the therapeutic potential of tES across various clinical conditions and the central role of sleep in restoration and memory consolidation, numerous studies have investigated its effects on sleep and sleep-related parameters, yielding inconsistent results. This systematic review provides an up-to-date synthesis of 51 studies assessing the impact of tES on objectively measured electrophysiological sleep outcomes in both healthy individuals and clinical populations. The reviewed studies demonstrate heterogeneous effects, reflecting substantial variability in study designs. Nonetheless, consistent trends emerge, including reduced NREM1 and increases in total sleep time, NREM2, and NREM3 following tES. Moreover, slow-oscillatory tES increased slow-wave power during sleep. Here we show that tES, particularly slow-oscillatory tES, may positively influence sleep architecture and continuity by modulating endogenous brain oscillations. However, due to heterogeneous stimulation protocols, inconsistent findings, the limited number of significant effects and substantial risk of bias the current evidence remains inconclusive. Well-designed, large-scale trials targeting specific sleep outcomes are needed to clarify the therapeutic potential of tES.
Brain insulin resistance and cerebrovascular dysfunction emerge early in late-onset Alzheimer's disease, but how amyloid-β (Aβ) disrupts insulin signaling at the cerebrovascular blood-brain barrier-a major site of insulin receptor signaling and transport into the brain-remains unclear. We exposed two distinct human blood-brain-barrier endothelial cell models to soluble Aβ40 or Aβ42 for 1 h, followed by 100 nM insulin for 10 min. Protein and phosphoprotein responses were quantified by reverse-phase protein array, and differential expression was evaluated using linear models. In hCMEC/D3 cells, Aβ40 reduced insulin-stimulated Akt activation and converted insulin's normal inhibition of AMPK into modest stimulation. Aβ42 did not alter insulin-stimulated Akt signaling but moderately suppressed basal Akt activation. Because the iBMEC model did not show insulin-induced activation of PI3K-Akt signaling, mechanistic interpretation of Aβ effects on insulin-responsive signaling focused on hCMEC/D3 cells. These findings identify acute Aβ40-sensitive impairment of insulin-responsive Akt signaling in hCMEC/D3 BBB endothelial cells. The results define candidate signaling nodes for further mechanistic study of Aβ effects on BBB insulin-signaling dysfunction.
Noninvasive neuromodulation methods are promising for treating neurological diseases, but generally have limited ability to selectively target deep brain structures such as the basal ganglia or hippocampus. Transcranial temporal Interference Stimulation (tTIS) overcomes this limitation by superimposing high-frequency electric fields to create low-frequency amplitude-modulated envelopes that can preferentially target deep brain structures. This review explores the operation principles and recent advances of tTIS aimed at improving its spatial accuracy and versatility. Additionally, we analyze the key aspects of tTIS system design, including waveform generation, high-voltage-compliant output stage, and real-time charge balancing, which collectively enable safe and efficient stimulation delivery. We further discuss key challenges such as safety, standardization, and long-term efficacy, and outline future directions toward personalized tTIS.
Peripheral vestibular stimulation elicits brainstem reflex responses manifesting as a vestibular-ocular reflex nystagmus ('VOR') and evokes a perception of self-motion or 'vertigo'. While VOR responses are objectively measured via eye movements, no such objective measure exists for assessing the cortical vestibular processing of self-motion. Understanding how the brain encodes vestibular-mediated self-motion could provide electrophysiological markers for clinical syndromes where reflex and perception are uncoupled, e.g. in vestibular agnosia. Hence, here we investigated the brain's encoding of bottom-up vestibular signals, using passive yaw-plane chair rotations performed in complete darkness with simultaneous EEG. Healthy controls (n = 8) were compared to patients with bilateral vestibulopathy (BVP), either with residual function (BVP-residual; n=6) or complete loss (BVP-complete; n=1), at five acceleration levels (range: 30-150º /s2). Comparing healthy controls with BVP-residual, we found: 1) no differences in time-frequency analyses; and 2) differences in vestibular evoked potentials magnitude (P < 0.01). Chair acceleration changes were consistently accompanied by phase-locked and induced (non-phase locked) theta-increases as well as alpha reduction in both, healthy and patients. Importantly, while the induced theta component was present in BVP-residual, it was absent in BVP-complete. Overall, findings indicate potential utility of: 1) vestibular evoked EEG responses for identifying attenuated vestibular signalling; and 2) theta activity as a cortical signature of preserved bottom-up vestibular signalling. These preliminary findings would require further investigation to confirm their functional role.
The rate of growth hormone (GH) deficiency (GHD) after traumatic brain injury (TBI) among children and adolescents remains uncertain, partly because of limited follow-up. To evaluate a novel diagnostic approach for post-TBI GHD based on height velocity (HV), IGF-1 levels, and response to recombinant human growth hormone (rhGH), and to estimate its incidence. In this prospective, longitudinal study, 31 patients (aged 2.4-18.6 years) hospitalized for TBI underwent complete clinical and hormonal evaluations every 3 months for ≥1 year. Eleven were excluded because they had reached their final or near-final height. The criteria for GHD diagnosis included (a) HV below -1 SDS, (b) at least one IGF-1 level below -1 SDS during the first 2 years after TBI, and (c) increase in HV (>2 SDS) and IGF-1 (>1 SDS) during rhGH therapy. Four patients met criteria for GHD. During the second year after TBI, HV-SDS ranged from -1.42 to -3.41, and height-SDS declined. All patients had at least one IGF-1 value below -1 SDS, while GH stimulation tests were often discordant with HV and IGF-1 levels. Therapy with rhGH led to marked increases in HV-SDS (≥2.73) and IGF-1-SDS (≥1.34) in all 4 patients. Fourteen children maintained normal HV, despite abnormal stimulation tests in some cases. Extended HV monitoring combined with IGF-1 assessment and therapeutic rhGH response was more effective than GH stimulation tests alone for diagnosing post-TBI GHD. The GHD incidence was 13%, underscoring the importance of extended auxological follow-up in pediatric patients after TBI.
Deep brain stimulation (DBS) has been shown to provide benefits for dystonia beyond 15 years. However, the long-term biological response to chronically implanted DBS hardware and its structural integrity over such extended periods remain poorly characterized. Pathological examination of explanted leads and especially those implanted for over a decade or more has been rarely performed. The aim was to document the pathological findings of bilaterally explanted globus pallidus pars interna (GPi) DBS leads after 15 years of continuous therapy in a patient with DYT-1 dystonia. We present the case of a 23-year-old woman with genetically confirmed DYT-1 dystonia who underwent bilateral GPi DBS implantation at the age of 8. After 15 years of stable therapeutic benefit, she experienced progressive functional decline despite extensive reprogramming attempts. Bilateral lead revision was performed, and the explanted DBS leads were examined macroscopically and microscopically. The explanted leads demonstrated striking macroscopic abnormalities, including membrane coating and mild contact degradation. Microscopic examination revealed extensive fibrous tissue encapsulation and adherent coagulated brain tissue, suggestive of a mild chronic foreign body response. The left DBS lead revealed a decreased electrical impedance, and this was correlated with contact degradation. Despite lead revision, no definitive symptom improvement occurred after 9 months. These findings suggest that DBS leads may maintain therapeutic function despite significant biological and structural changes over a 15-year period. Hardware integrity in this case did not correlate with clinical effectiveness.
The recovery of motor function in patients with ischemic stroke is closely related to the plastic remodeling of cortical functional networks. Low-intensity transcranial ultrasound stimulation (TUS) has been shown to improve motor behavior in patients with ischemic stroke and modulate cortical functional networks in healthy individuals. However, whether motor improvement after TUS is associated with cortical functional network reorganization remains unclear. Therefore, in this study, we constructed a mouse model of ischemic stroke using male C57BL/6 mice and simultaneously recorded the local field potential and gait behavior data of the whole-brain cortex of mice in a free-walking state before and after ultrasound intervention. Gait parameters, cortical functional network connectivity, and topology were systematically analyzed, and the correlations between behavioral indicators and network connectivity were explored. Our findings revealed that TUS significantly improved motor function in the mouse model, modulated cortical functional network connectivity to restore it to a healthy state, enhanced global information integration ability, optimized local separation efficiency, and restored gait phase transition control. Furthermore, the TUS-induced changes in the cortical functional network were positively correlated with behavioral improvement. This study confirmed that motor improvement after low-intensity TUS is accompanied by cortical functional network reorganization, and that such reorganization may contribute to post-stroke functional recovery.Significance Statement Stroke disrupts the neural networks essential for maintaining gait coordination. Although low-intensity TUS stimulation can improve post-stroke motor performance, how it remodels and restores cortical functional network connectivity during natural behavior remains unclear. This study combined free-walking gait with simultaneous acquisition of cortical local field potentials to conduct a 7-day targeted ultrasound modulation intervention in the infarct area in ischemic stroke mice. Results showed that TUS significantly improved gait and induced gait-phase-specific cortical functional network connectivity reconnection. This study provides evidence for the neural mechanisms by which ultrasound promotes post-stroke motor function recovery and offers a theoretical basis for the translational application of TUS in stroke treatment.
Working memory (WM) is a capacity-limited control system that maintains and updates task-relevant representations for goal-directed cognition. Because WM declines with aging and is disrupted across neuropsychiatric and neurodegenerative disorders, neuromodulation has emerged as both a causal probe of circuit function and a potential therapeutic adjunct. This mechanistic narrative review evaluates evidence across transcranial direct current stimulation, transcranial magnetic stimulation/theta-burst stimulation, transcranial alternating current stimulation, transcranial random noise stimulation, and deep brain stimulation. Rather than asking whether neuromodulation uniformly enhances WM, we examine when different modalities alter distinct WM subprocesses. Across modalities, effects are generally modest and heterogeneous, but the literature increasingly suggests that stimulation acts less by adding "capacity" than by biasing gain, timing, and plasticity-related control variables that shape WM trajectories. More precise dosing, targeting, and computation-aligned outcomes are needed to establish reproducible and mechanistically interpretable effects.