Neuromodulation最新文献

Objectives: Epidural stimulation of the spinal cord evokes distinct electrophysiologic responses that can be recorded epidurally. Here, we characterized evoked compound action potentials (ECAPs), doublets (secondary or tertiary ECAPs, probably of different physiologic origin from primary ECAPs), evoked synaptic activity potentials (ESAPs), and electromyographic (EMG) signals in preclinical models. Our objective was to clarify the features and distinct physiologic origins of these signals, to advance mechanistic studies and support clinical applications of spinal cord stimulation (SCS) therapy.

Materials and methods: Adult male Sprague-Dawley rats (300-440 g) were implanted with two epidural leads (caudal and rostral; each with eight electrodes) and received monopolar, biphasic stimulation (200-μs pulse width) at 2 and 50 Hz, with current increased stepwise to motor threshold. Rhesus macaques (11.5 and 10.2 kg) were implanted with a single 12-electrode epidural lead and stimulated using either tripolar, triphasic pulses at 10 Hz (100 μs) or tripolar, biphasic pulses at 3 Hz (80 μs) up to 3 × ECAP threshold. Recordings were taken from nonstimulating electrodes.

Results: ECAPs and EMG signals were recorded across multiple spinal segments in both rats (L1-T7) and macaques (L2-T11). Doublets presented as complex waveforms with multiple negative peaks, two in rats and three in macaques, likely representing distinct ECAPs at T11-T6 in a rat and L1-T11 in macaques. ESAPs, detectable in rats, showed anatomical specificity over the L1/T13 vertebrae, with peak responses at L1. Signal analysis included activation thresholds, amplitudes, latencies, and conduction velocities.

Conclusions: This study outlines electrophysiologic signals evoked by SCS in terms of their waveform, recruitment thresholds, and putative physiologic origins. We propose that to some extent, these signals reflect different aspects of spinal processing and may serve as biomarkers of dysregulated nociceptive pathways, and as indicators of SCS efficacy or potential side effects.

Introduction: Photobiomodulation (PBM) uses light to modulate biological activity. Because red and near-infrared wavelengths penetrate the skin and skull, PBM can be applied transcranially (tPBM) to noninvasively modulate brain activity, offering therapeutic potential for neurologic, psychiatric, neurodevelopmental, neurodegenerative, and neuroimmunologic disorders, and for cognitive enhancement.

Materials and methods: A scoping review is performed integrating literature on tPBM in humans, excluding indications for which only preclinical data exist.

Results: tPBM can be delivered through the scalp, nose, oral cavity, or external ear canal, in continuous or pulsed modes, with varying wavelengths and doses. It exhibits a biphasic dose-response, meaning both under- and overstimulation are possible. tPBM directly enhances cellular energy metabolism, oxygenation, and neuroprotection by stimulating mitochondria, promoting repair, reducing apoptosis, and modulating neuroinflammation. It supports neurogenesis, synaptogenesis, angiogenesis, and microtubule plasticity, and activates the glymphatic clearance system. Additional effects include transient receptor potential vanilloid 1 calcium channel modulation, intercellular mitochondrial transfer, and immune cell recruitment. Preclinical studies indicate benefits in epilepsy, hypoxic-ischemic lesions, intraventricular hemorrhage, and posttraumatic stress disorder, whereas clinical studies cover stroke, traumatic brain injury, chronic traumatic encephalopathy, autism spectrum disorder, attention-deficit/hyperactivity disorder, Down syndrome, Alzheimer's and Parkinson's diseases, anxiety, depression, insomnia, sexual dysfunction, and multiple sclerosis.

Discussion and perspective: Optimal tPBM outcomes may depend on multitarget, multiwavelength approaches, and pulsed delivery, likely owing to complementary mechanisms and prevention of excessive reactive oxygen species production. Understanding the full range of illumination parameters is essential to develop personalized protocols. Future research should determine whether tPBM can serve as a standalone therapy or as part of multimodal interventions including pharmacology, psychotherapy, or other neuromodulation techniques.

Background: Generalized anxiety disorder (GAD) affects approximately 4% of the global population. Current treatment methods, for example, pharmacology and psychotherapy, are insufficient owing to side effects and a lack of efficacy and accessibility, highlighting the need for better therapeutic options. Studies have identified electrical vestibular nerve stimulation (VeNS) as a potential novel treatment method.

Objectives/hypothesis: Participants using a VeNS device will show superior improvement in GAD (GAD-7) score after 28 days of use to those receiving sham stimulation. Secondary outcomes were change in Insomnia Severity Index (ISI) and the 36-Item Short Form Health Survey (SF-36) scores (eight components).

Materials and methods: In this double-blind, randomized, sham-controlled study, N = 87 participants with a GAD-7 score ≥10 were allocated a VeNS or sham device (1:1 ratio). Participants were asked to complete daily 30-minute stimulation sessions at home for 28 days. Data were statistically analyzed using an intention-to-treat approach.

Results: The change in GAD-7 score from baseline to day 28 in those who presented at baseline with a GAD-7 score ≥5 was not statistically significant between the sham and treatment groups (3.90 ± 4.09 and 4.95 ± 4.32, sham and treatment groups, respectively; p = 0.269). Subgroup analysis of participants with moderate/severe GAD (GAD-7 score ≥10) showed a significantly greater improvement in GAD-7 score in the treatment group than in the sham group (intention to treat p = 0.045). There was no significant difference between intervention groups in improvement in either ISI score or SF-36 components in the moderate/severe anxiety group (GAD-7 score ≥10).

Conclusions: VeNS is a low-risk, noninvasive therapy that has the potential to alleviate the symptoms of moderate-to-severe GAD.

Clinical trial registration: The Clinicaltrials.gov registration number for the study is NCT05907967.

Introduction: The field of spinal cord stimulation (SCS) is characterized by the availability of multiple stimulation paradigms and device options, yet limited evidence exists on ways health care providers make decisions during clinical reasoning. This study aimed to explore health care providers' opinions and reasoning during the decision-making process in SCS therapy, focusing on factors influencing the choice of stimulation paradigm and manufacturer.

Materials and methods: An online survey was distributed among health care professionals involved in neuromodulation for pain through the North American Neuromodulation Society newsletter and during the 2nd Pain Academy in Madrid (2024). Health care professionals were asked to indicate the reasoning behind the decision-making on which type of SCS will be implanted, and from which manufacturer devices will be implanted.

Results: A total of 102 respondents completed the survey, of whom 90 were clinical practitioners or nurses and included in the analysis. The first major decision typically concerned the selection of the stimulation paradigm (39.8%), primarily influenced by patient pathology and characteristics. The choice of manufacturer was primarily determined by the level of technical support and service. Paresthesia-based SCS remained widely used (64.6%), yet paresthesia-free stimulation was more often used (86.6%). Magnetic resonance imaging (MRI) conditionality and other extraparadigm features also were identified as relevant determinants in device selection.

Discussion: Decision-making in SCS shows substantial variability among health care providers. Although implanters generally hold final responsibility, factors such as patient characteristics, manufacturer support, and MRI conditionality play a major role in guiding clinical choices. These findings underscore the need for clearer decision frameworks, transparent reasoning, and greater multidisciplinary involvement in SCS therapy selection.