Neuronal biomarkers of Parkinson's disease are present in healthy aging

The prevalence of Parkinson's disease (PD) increases with aging and both processes share similar cellular mechanisms and alterations in the dopaminergic system. Yet it remains to be investigated whether aging can also demonstrate electrophysiological neuronal signatures typically associated with PD. Previous work has shown that phase-amplitude coupling (PAC) between the phase of beta oscillations and the amplitude of gamma oscillations as well as beta bursts features can serve as electrophysiological biomarkers for PD. Here we hypothesize that these metrics are also present in apparently healthy elderly subjects. Using resting state multichannel EEG measurements, we show that PAC between beta oscillation and broadband gamma activity (50–150 Hz) is elevated in a group of elderly (59–77 years) compared to young volunteers (20–35 years) without PD. Importantly, the increase of PAC is statistically significant even after ruling out confounds relating to changes in spectral power and non-sinusoidal shape of beta oscillation. Moreover, a trend for a higher percentage of longer beta bursts (> 0.2 s) along with the increase in their incidence rate is also observed for elderly subjects. Using inverse modeling, we further show that elevated PAC and longer beta bursts are most pronounced in the sensorimotor areas. Moreover, we show that PAC and longer beta bursts might reflect distinct mechanisms, since their spatial patterns only partially overlap and the correlation between them is weak. Taken together, our findings provide novel evidence that electrophysiological biomarkers of PD may already occur in apparently healthy elderly subjects. We hypothesize that PAC and beta bursts characteristics in aging might reflect a pre-clinical state of PD and suggest their predictive value to be tested in prospective longitudinal studies

Neural excitability and sensory input determine intensity perception with opposing directions in initial cortical responses

Perception of sensory information is determined by stimulus features (e.g., intensity) and instantaneous neural states (e.g., excitability). Commonly, it is assumed that both are reflected similarly in evoked brain potentials, that is, larger amplitudes are associated with a stronger percept of a stimulus. We tested this assumption in a somatosensory discrimination task in humans, simultaneously assessing (i) single-trial excitatory post-synaptic currents inferred from short-latency somatosensory evoked potentials (SEPs), (ii) pre-stimulus alpha oscillations (8-13 Hz), and (iii) peripheral nerve measures. Fluctuations of neural excitability shaped the perceived stimulus intensity already during the very first cortical response (at ~20 ms) yet demonstrating opposite neural signatures as compared to the effect of presented stimulus intensity. We reconcile this discrepancy via a common framework based on the modulation of electro-chemical membrane gradients linking neural states and responses, which calls for reconsidering conventional interpretations of brain potential magnitudes in stimulus intensity encoding

Oscillatory Source Tensor Discriminant Analysis (OSTDA): A regularized tensor pipeline for SSVEP-based BCI systems

Periodic signals called Steady-State Visual Evoked Potentials (SSVEP) are elicited in the brain by flickering stimuli. They are usually detected by means of regression techniques that need relatively long trial lengths to provide feedback and/or sufficient number of calibration trials to be reliably estimated in the context of brain-computer interface (BCI). Thus, for BCI systems designed to operate with SSVEP signals, reliability is achieved at the expense of speed or extra recording time. Furthermore, regardless of the trial length, calibration free regression-based methods have been shown to suffer from significant performance drops when cognitive perturbations are present affecting the attention to the flickering stimuli. In this study we present a novel technique called Oscillatory Source Tensor Discriminant Analysis (OSTDA) that extracts oscillatory sources and classifies them using the newly developed tensor-based discriminant analysis with shrinkage. The proposed approach is robust for small sample size settings where only a few calibration trials are available. Besides, it works well with both low- and high-number-of-channel settings, using trials as short as one second. OSTDA performs similarly or significantly better than other three benchmarked state-of-the-art techniques under different experimental settings, including those with cognitive disturbances (i.e. four datasets with control, listening, speaking and thinking conditions). Overall, in this paper we show that OSTDA is the only pipeline among all the studied ones that can achieve optimal results in all analyzed conditions

Harmoni: A method for eliminating spurious interactions due to the harmonic components in neuronal data

Cross-frequency synchronization (CFS) has been proposed as a mechanism for integrating spatially and spectrally distributed information in the brain. However, investigating CFS in Magneto- and Electroencephalography (MEG/EEG) is hampered by the presence of spurious neuronal interactions due to the non-sinusoidal waveshape of brain oscillations. Such waveshape gives rise to the presence of oscillatory harmonics mimicking genuine neuronal oscillations. Until recently, however, there has been no methodology for removing these harmonics from neuronal data. In order to address this long-standing challenge, we introduce a novel method (called HARMOnic miNImization - Harmoni) that removes the signal components which can be harmonics of a non-sinusoidal signal. Harmoni’s working principle is based on the presence of CFS between harmonic components and the fundamental component of a non-sinusoidal signal. We extensively tested Harmoni in realistic EEG simulations. The simulated couplings between the source signals represented genuine and spurious CFS and within-frequency phase synchronization. Using diverse evaluation criteria, including ROC analyses, we showed that the within- and cross-frequency spurious interactions are suppressed significantly, while the genuine activities are not affected. Additionally, we applied Harmoni to real resting-state EEG data revealing intricate remote connectivity patterns which are usually masked by the spurious connections. Given the ubiquity of non-sinusoidal neuronal oscillations in electrophysiological recordings, Harmoni is expected to facilitate novel insights into genuine neuronal interactions in various research fields, and can also serve as a steppingstone towards the development of further signal processing methods aiming at refining within- and cross-frequency synchronization in electrophysiological recordings

Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age

While many structural and biochemical changes in the brain have been previously associated with aging, the findings concerning electrophysiological signatures, reflecting functional properties of neuronal networks, remain rather controversial. To try resolve this issue, we took advantage of a large population study (N=1703) and comprehensively investigated the association of multiple EEG biomarkers (power of alpha and theta oscillations, individual alpha peak frequency (IAF), the slope of 1/f power spectral decay), aging, and aging and cognitive performance. Cognitive performance was captured with three factors representing processing speed, episodic memory, and interference resolution. Our results show that not only did IAF decline with age but it was also associated with interference resolution over multiple cortical areas. To a weaker extent, 1/f slope of the PSD showed age-related reductions, mostly in frontal brain regions. Finally, alpha power was negatively associated with the speed of processing in the right frontal lobe, despite the absence of age-related alterations. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered when investigating the association between age, neuronal activity, and cognitive performance

Higher order spectral regression discriminant analysis (HOSRDA): A tensor feature reduction method for ERP detection

Tensors are valuable tools to represent Electroencephalogram (EEG) data. Tucker decomposition is the most used tensor decomposition in multidimensional discriminant analysis and tensor extension of Linear Discriminant Analysis (LDA), called Higher Order Discriminant Analysis (HODA), is a popular tensor discriminant method used for analyzing Event Related Potentials (ERP). In this paper, we introduce a new tensor-based feature reduction technique, named Higher Order Spectral Regression Discriminant Analysis (HOSRDA), for use in a classification framework for ERP detection. The proposed method (HOSRDA) is a tensor extension of Spectral Regression Discriminant Analysis (SRDA) and casts the eigenproblem of HODA to a regression problem. The formulation of HOSRDA can open a new framework for adding different regularization constraints in higher order feature reduction problem. Additionally, when the dimension and number of samples is very large, the regression problem can be solved via efficient iterative algorithms. We applied HOSRDA on data of a P300 speller from BCI competition III and reached average character detection accuracy of 96.5% for the two subjects. HOSRDA outperforms almost all of other reported methods on this dataset. Additionally, the results of our method are fairly comparable with those of other methods when 5 and 10 repetitions are used in the P300 speller paradigm

中研院地科所建築物強震資料分析及強地動觀測網地震資料在地震危害度分析中之應用

Cross-frequency coupling (CFC) between neuronal oscillations reflects an integration of spatially and spectrally distributed information in the brain. Here, we propose a novel framework for detecting such interactions in Magneto- and Electroencephalography (MEG/EEG), which we refer to as Nonlinear Interaction Decomposition (NID). In contrast to all previous methods for separation of cross-frequency (CF) sources in the brain, we propose that the extraction of nonlinearly interacting oscillations can be based on the statistical properties of their linear mixtures. The main idea of NID is that nonlinearly coupled brain oscillations can be mixed in such a way that the resulting linear mixture has a non-Gaussian distribution. We evaluate this argument analytically for amplitude-modulated narrow-band oscillations which are either phase-phase or amplitude-amplitude CF coupled. We validated NID extensively with simulated EEG obtained with realistic head modelling. The method extracted nonlinearly interacting components reliably even at SNRs as small as dB. Additionally, we applied NID to the resting-state EEG of 81 subjects to characterize CF phase-phase coupling between alpha and beta oscillations. The extracted sources were located in temporal, parietal and frontal areas, demonstrating the existence of diverse local and distant nonlinear interactions in resting-state EEG data. All codes are available publicly via GitHub