Cross-frequency coupling (CFC) reflects (nonlinear) interactions between signals of different frequencies. Evidence from both patient and healthy participant studies suggests that CFC plays an essential role in neuronal computation, interregional interaction, and disease pathophysiology. The present review discusses methodological advances and challenges in the computation of CFC with particular emphasis on potential solutions to spurious coupling, inferring intrinsic rhythms in a targeted frequency band, and causal interferences. We specifically focus on the literature exploring CFC in the context of cognition/memory tasks, sleep, and neurological disorders, such as Alzheimer's disease, epilepsy, and Parkinson's disease. Furthermore, we highlight the implication of CFC in the context and for the optimization of invasive and noninvasive neuromodulation and rehabilitation. Mainly, CFC could support advancing the understanding of the neurophysiology of cognition and motor control, serve as a biomarker for disease symptoms, and leverage the optimization of therapeutic interventions, e.g., closed-loop brain stimulation. Despite the evident advantages of CFC as an investigative and translational tool in neuroscience, further methodological improvements are required to facilitate practical and correct use in cyborg and bionic systems in the field.

Gait disturbance in Parkinson’s disease (PD) can be ameliorated by sound stimulation. Given that excessive β synchronization in basal ganglia is linked to motor impairment in PD, whether the frequency nesting interactions are associated with the gait problem is far from clear. To this end, the masking phase-amplitude coupling (PAC) method was proposed to overcome the trade-off between intrinsic nonlinearity/non-stationarity and demand for predetermined frequencies, normally extracted by the filter. In this study, we analyzed LFPs recorded from 13 patients (one female) with PD during stepping with bilateral deep brain electrodes implanted in the subthalamic nucleus (STN). We found that not only high-frequency oscillation (100–300 Hz) was modulated by β (13–30 Hz) but also β and γ amplitude were modulated by their low-frequency components in δ/θ/α and δ/θ/α/β bands. These PAC values were suppressed by sound stimulation, along with an improvement in gait. We also showed that gait-related high-β (Hβ) modulation in the STN was sensitive to auditory cues, and Hβ gait-phase modulation increased with a metronome. Meanwhile, phase-locking values (PLVs) across all frequencies were significantly suppressed around contralateral heel strikes, manifesting the contralateral step as a critical gait phase in gait initiation for PD. Only the PLVs around contralateral steps were sensitive to auditory cues. Our results support masking PAC as an effective method in exploring frequency nesting interactions in LFPs and reveal the linkages between sound stimulation and couplings related to gait phases in the STN. These findings raise the possibility that nesting interactions in the STN work as feasible biomarkers in alleviating gait disorders.

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Hollow nanocone arrays are fabricated by a low-cost and efficient colloidal lithography (CL) technique. The hollow nanocone arrays are then reversed to make only the tips contact the substrate. The optical properties of the obverse and inverse hollow nanocone arrays are determined by the surrounding environment, showing different reflection spectra and structure dependence. The inverse hollow nanocone arrays show a relative index sensitivity of 70% per RIU with strict linearity. The fluorescence of fluorophore or staining cells can be facilely enhanced by placing them on the tips of the hollow nanocone arrays, while having no quenching effect. The study of the obverse and inverse hollow nanocone arrays can benefit the understanding of the effect of the environment on the plasmonic resonances. The hollow nanocone arrays are promising to serve as high-performance plasmonic sensors and versatile substrates for surface-enhanced fluorescence imaging.