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Extremely low-frequency, low-intensity electromagnetic field (ELF-EMF) therapy is a non-invasive brain stimulation method that can modulate neuroprotection and neuroplasticity. ELF-EMF was recently shown to enhance recovery in human stroke in a small pilot clinical trial (NCT04039178). ELF-EMFs encompass a wide range of frequencies, typically ranging from 1 to 100 Hz, and their effects can vary depending on the specific frequency employed. However, whether and to what extent the effectiveness of ELF-EMFs depends on the frequency remains unclear. In the present study, we aimed to assess the efficacy of different frequency-intensity protocols of ELF-EMF in promoting functional recovery in a mouse cortical stroke model with treatment initiated 4 days after the stroke, employing a series of motor behavior tests. Our findings demonstrate that a theta-frequency ELF-EMF (5 Hz) effectively enhances functional recovery in a reach-to-grasp task, whereas neither gamma-frequency (40 Hz) nor combination frequency (5-16-40 Hz) ELF-EMFs induce a significant effect. Importantly, our histological analysis reveals that none of the ELF-EMF protocols employed in our study affect infarct volume, inflammatory, or glial activation, suggesting that the observed beneficial effects may be mediated through non-neuroprotective mechanisms. Our data indicate that ELF-EMFs have an influence on functional recovery after stroke, and this effect is contingent upon the specific frequency used. These findings underscore the critical importance of optimizing the protocol parameters to maximize the beneficial effects of ELF-EMF. Further research is warranted to elucidate the underlying mechanisms and refine the protocol parameters for optimal therapeutic outcomes in stroke rehabilitation.
RESUMEN
Background and purpose: Impaired upper extremity (UE) motor function is a common disability after ischemic stroke. Exposure to extremely low frequency and low intensity electromagnetic fields (ELF-EMF) in a frequency-specific manner (Electromagnetic Network Targeting Field therapy; ENTF therapy) is a non-invasive method available to a wide range of patients that may enhance neuroplasticity, potentially facilitating motor recovery. This study seeks to quantify the benefit of the ENTF therapy on UE motor function in a subacute ischemic stroke population. Methods: In a randomized, sham-controlled, double-blind trial, ischemic stroke patients in the subacute phase with moderately to severely impaired UE function were randomly allocated to active or sham treatment with a novel, non-invasive, brain computer interface-based, extremely low frequency and low intensity ENTF therapy (1-100 Hz, < 1 G). Participants received 40 min of active ENTF or sham treatment 5 days/week for 8 weeks; ~three out of the five treatments were accompanied by 10 min of concurrent physical/occupational therapy. Primary efficacy outcome was improvement on the Fugl-Meyer Assessment - Upper Extremity (FMA-UE) from baseline to end of treatment (8 weeks). Results: In the per protocol set (13 ENTF and 8 sham participants), mean age was 54.7 years (±15.0), 19% were female, baseline FMA-UE score was 23.7 (±11.0), and median time from stroke onset to first stimulation was 11 days (interquartile range (IQR) 8-15). Greater improvement on the FMA-UE from baseline to week 4 was seen with ENTF compared to sham stimulation, 23.2 ± 14.1 vs. 9.6 ± 9.0, p = 0.007; baseline to week 8 improvement was 31.5 ± 10.7 vs. 23.1 ± 14.1. Similar favorable effects at week 8 were observed for other UE and global disability assessments, including the Action Research Arm Test (Pinch, 13.4 ± 5.6 vs. 5.3 ± 6.5, p = 0.008), Box and Blocks Test (affected hand, 22.5 ± 12.4 vs. 8.5 ± 8.6, p < 0.0001), and modified Rankin Scale (-2.5 ± 0.7 vs. -1.3 ± 0.7, p = 0.0005). No treatment-related adverse events were reported. Conclusions: ENTF stimulation in subacute ischemic stroke patients was associated with improved UE motor function and reduced overall disability, and results support its safe use in the indicated population. These results should be confirmed in larger multicenter studies. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04039178, identifier: NCT04039178.
RESUMEN
This review outlines developments in the growth of crystalline oxides on the ubiquitous silicon semiconductor platform. The overall goal of this endeavor is the integration of multifunctional complex oxides with advanced semiconductor technology. Oxide epitaxy in materials systems achieved through conventional deposition techniques is described first, followed by a description of the science and technology of using atomic layer-by-layer deposition with molecular beam epitaxy (MBE) to systematically construct the oxide-silicon interface. An interdisciplinary approach involving MBE, advanced real-space structural characterization, and first-principles theory has led to a detailed understanding of the process by which the interface between crystalline oxides and silicon forms, the resulting structure of the interface, and the link between structure and functionality. Potential applications in electronics and photonics are also discussed.