Background: Exposure to 40 Hz stroboscopic light, for one hour a day, has previously been published as a potential treatment option for Alzheimer’s disease in animal models. However, exposure for an hour a day to 40 Hz stroboscopic light can be strenuous and examining other types of 40 Hz inducing stimuli is paramount if chronic treatment is wanted. Objective: A core assumption behind ensuring a therapeutic outcome is that the visual stimuli can induce 40 Hz gamma entrainment. Here, we examine whether a specific visual stimulus, 40 Hz invisible spectral flicker (ISF), can induce gamma entrainment and how it differs from both continuous light (CON) and 40 Hz stroboscopic light (STROBE). Methods: The study included non-simultaneous EEG-fMRI neuroimaging of 13 young healthy volunteers during light exposure. Each light condition (i.e., CON, ISF, or STROBE) was active for 30 seconds followed immediately by the next. Results: Entrainment of 40 Hz neural activity were significantly higher signal-to-noise ratio during exposure to ISF (mean: 3.03, 95% CI 2.07 to 3.99) and STROBE (mean: 12.04, 95% CI 10.18 to 13.87) compared to CON. Additionally STROBE had a higher entrainment than ISF (mean: 9.01, 95% CI 7.16 to 12.14). Conclusion: This study presents a novel method of 40 Hz entrainment using ISF. This enables the possibility of future randomized placebo-controlled clinical trials with acceptable double blinding due to the essentially imperceivable flicker, which is expected to substantially reduce discomfort compared to interventions with stroboscopic flicker.

Laser printing with a spatial light modulator (SLM) has several advantages over conventional raster-writing and dot-matrix display (DMD) writing: multiple pixel exposure, high power endurance and existing software for computer generated holograms (CGH). We present a technique for the design and manufacturing of plasmonic metasurfaces based on ultrafast laser printing with an SLM. As a proof of principle, we have used this technique to laser print a plasmonic metalens as well as high resolution plasmonic color decorations. The high throughput holographic resonant laser printing (HRLP) approach enables on-demand mass-production of customized metasurfaces.

Background: Recent studies suggested induction of 40 Hz neural activity as a potential treatment for Alzheimer’s disease (AD). However, prolonged exposure to flickering light raises adherence and safety concerns, encouraging investigation of tolerable light stimulation protocols. Objective: To investigate the safety, feasibility, and exploratory measures of efficacy. Methods: This two-stage randomized placebo-controlled double-blinded clinical trial, recruited first cognitive healthy participants (n = 3/2 active/placebo), and subsequently patients with mild-to-moderate AD (n = 5/6, active/placebo). Participants were randomized 1:1 to receive either active intervention with 40 Hz Invisible Spectral Flicker (ISF) or placebo intervention with color and intensity matched non-flickering white light. Results: Few and mild adverse events were observed. Adherence was above 86.1% of intended treatment days, with participants remaining in front of the device for >51.3 min (60 max) and directed gaze >34.9 min. Secondary outcomes of cognition indicate a tendency towards improvement in the active group compared to placebo (mean: –2.6/1.5, SD: 6.58/6.53, active/placebo) at week 6. Changes in hippocampal and ventricular volume also showed no tendency of improvement in the active group at week 6 compared to placebo. At week 12, a potential delayed effect of the intervention was seen on the volume of the hippocampus in the active group compared to placebo (mean: 0.34/–2.03, SD: 3.26/1.18, active/placebo), and the ventricular volume active group (mean: –0.36/2.50, SD: 1.89/2.05, active/placebo), compared to placebo. Conclusion: Treatment with 40 Hz ISF offers no significant safety or adherence concerns. Potential impact on secondary outcomes must be tested in larger scale clinical trials.

We report on a polarization-dependent plasmonic aluminumbased high-density metasurface operating at blue wavelengths. The fabricated sub-wavelength structures, tailored in size and geometry, possess strong, localized, plasmonic resonances able to control linear polarization. Best performance is achieved by rotating an elongated rectangular structure of length 180 nm and width 110 nm inside a square lattice of period 250 nm. In the case of 45 degrees rotation of the structure with respect to the lattice, the normal-incidence reflectance drops around the resonance wavelength of 457 nm from about 60 percent to below 2 percent. A. 106, 19227-19232 (2009). 9. X. Zhu, S. Xiao, L. Shi, X. Liu, J. Zi, O. Hansen, and N. A. Mortensen, "A stretch-tunable plasmonic structure with a polarization-dependent response," Opt. Express 20, 5237 (2012). 10. W. Chen, M. Tymchenko, P. Gopalan, X. Ye, Y. Wu, M. Zhang, C. B. Murray, A. Alu, and C. R. Kagan, "Largearea nanoimprinted colloidal Au nanocrystal-based nanoantennas for ultrathin polarizing plasmonic metasurfaces," Nano Lett. 15, 5254-5260 (2015). 11.

Alzheimer's disease (AD) not only takes an emotional toll on the individual with the disease, their families, relatives, and caretakers, it also has immense socioeconomic consequences on the health care system and society. Moreover, the socioeconomic consequences are expected to increase significantly, thus reducing the social and economic cost of AD is of high importance. Recently, exposure to 40 Hz stroboscopic light therapy, for one hour a day, resulted in slowing the progression of AD in mice and has a considerable potential for treatment in humans. However, exposure to such stroboscopic light carries its own consequences being that it is difficult to implement in a patient's daily routine, irksome to use, and can cause visual discomfort which may result in a lack of patient adherence. Here, we demonstrate a novel technology based on controlling multiple single-color LEDs to produce white light where its spectral composition alternates at a given modulation frequency without visible flicker. We coin this technique as Invisible Spectral Flicker (ISF). We present 40 Hz invisible spectral flicker light as a potential alternative in reducing discomfort compared to 40 Hz stroboscopic light, whilst still entraining oscillations in various areas of the brain. Furthermore, we demonstrate a distinct way to generate a 40 Hz metameric light source with the presented color mixing scheme, and validate that the CIE 1931 (x, y) coordinates match for two different spectral power distributions. Finally, we illustrate the light characteristics of seven 40 Hz color fusion light sources and two 40 Hz stroboscopic light sources. The technology presented here will lead to new, and hopefully improved, designs of light therapy systems for the treatment of Alzheimer's and dementia.