Phase Of Low Frequency Oscillations Research Articles

Abnormal gamma phase-amplitude coupling in the parahippocampal cortex is associated with network hyperexcitability in Alzheimer's disease.

While animal models of Alzheimer's disease (AD) have shown altered gamma oscillations (∼40 Hz) in local neural circuits, the low signal-to-noise ratio of gamma in the resting human brain precludes its quantification via conventional spectral estimates. Phase-amplitude coupling (PAC) indicating the dynamic integration between the gamma amplitude and the phase of low-frequency (4-12 Hz) oscillations is a useful alternative to capture local gamma activity. In addition, PAC is also an index of neuronal excitability as the phase of low-frequency oscillations that modulate gamma amplitude, effectively regulates the excitability of local neuronal firing. In this study, we sought to examine the local neuronal activity and excitability using gamma PAC, within brain regions vulnerable to early AD pathophysiology-entorhinal cortex and parahippocampus, in a clinical population of patients with AD and age-matched controls. Our clinical cohorts consisted of a well-characterized cohort of AD patients (n = 50; age, 60 ± 8 years) with positive AD biomarkers, and age-matched, cognitively unimpaired controls (n = 35; age, 63 ± 5.8 years). We identified the presence or the absence of epileptiform activity in AD patients (AD patients with epileptiform activity, AD-EPI+, n = 20; AD patients without epileptiform activity, AD-EPI-, n = 30) using long-term electroencephalography (LTM-EEG) and 1-hour long magnetoencephalography (MEG) with simultaneous EEG. Using the source reconstructed MEG data, we computed gamma PAC as the coupling between amplitude of the gamma frequency (30-40 Hz) with phase of the theta (4-8 Hz) and alpha (8-12 Hz) frequency oscillations, within entorhinal and parahippocampal cortices. We found that patients with AD have reduced gamma PAC in the left parahippocampal cortex, compared to age-matched controls. Furthermore, AD-EPI+ patients showed greater reductions in gamma PAC than AD-EPI- in bilateral parahippocampal cortices. In contrast, entorhinal cortices did not show gamma PAC abnormalities in patients with AD. Our findings demonstrate the spatial patterns of altered gamma oscillations indicating possible region-specific manifestations of network hyperexcitability within medial temporal lobe regions vulnerable to AD pathophysiology. Greater deficits in AD-EPI+ suggests that reduced gamma PAC is a sensitive index of network hyperexcitability in AD patients. Collectively, the current results emphasize the importance of investigating the role of neural circuit hyperexcitability in early AD pathophysiology and explore its potential as a modifiable contributor to AD pathobiology.

High-Gamma Activity Is Coupled to Low-Gamma Oscillations in Precentral Cortices and Modulates with Movement and Speech.

Planning and executing motor behaviors requires coordinated neural activity among multiple cortical and subcortical regions of the brain. Phase-amplitude coupling between the high-gamma band amplitude and the phase of low frequency oscillations (theta, alpha, beta) has been proposed to reflect neural communication, as has synchronization of low-gamma oscillations. However, coupling between low-gamma and high-gamma bands has not been investigated. Here, we measured phase-amplitude coupling between low- and high-gamma in monkeys performing a reaching task and in humans either performing finger-flexion or word-reading tasks. We found significant coupling between low-gamma phase and high-gamma amplitude in multiple sensorimotor and premotor cortices of both species during all tasks. This coupling modulated with the onset of movement. These findings suggest that interactions between the low and high gamma bands are markers of network dynamics related to movement and speech generation.

Parameter identification of oscillations in power systems based on improved variational modal decomposition and HTLS-adaline method

Oscillation has become one of the important problems faced by modern power grids. Multi-types of oscillations may occur simultaneously in the power system and the oscillation frequency span is extremely large. For signals with wide-band oscillation modes, the signals in different frequency bands are first separated by a band-pass filter, and then the Improved Variational Mode Decomposition (IVMD) method with high noise robustness is used to extract each oscillating mode signal. Finally, the combinations of Hankel total least squares (HTLS) and adaptive neural network algorithm (Adaline ANN) is used to estimate the frequency, attenuation factor, amplitude and phase of low-frequency oscillations. Furthermore, the introduction of Adaline neural network solves the problem that the mode amplitude and phase are difficult to determine after IVMD processing, so that the detection accuracy is improved. Simulation and case analysis show that this method can effectively distinguish and extract different types of oscillation modes in the signal, and accurately identify the information of each mode. The IVMD-HTLS-Adaline method can effectively identify signals that have experienced severe oscillations or noise-like signals with potential oscillations.

Neuronal Oscillatory Signatures in the Developing Mouse Visual Cortex After Short-Term Monocular Deprivation.

Development and maturation in cortical networks depend on neuronal activity. For stabilization and pruning of connections, synchronized oscillations play a crucial role. A fundamental mechanism that enables coordinated activity during brain functioning is formed of synchronized neuronal oscillations in low- (delta and theta) and high- (gamma) frequency bands. The relationship between neural synchrony, cognition, and the perceptual process has been widely studied, but any possible role of neural synchrony in amblyopia has been less explored. We hypothesized that monocular deprivation (MD) during early postnatal life would lead to changes in neuronal activity that would be demonstrated by changes in phase-amplitude coupling (PAC) and altered power in specific oscillatory frequency. Our results demonstrate that functional connectivity in the visual cortex is altered by MD during adolescence. The amplitude of high-frequency oscillations is modulated by the phase of low-frequency oscillations. Demonstration of enhanced delta-gamma and theta-gamma PAC indicates that our results are relevant for a broad range of nested oscillatory markers. These markers are inherent to neuronal processing and are consistent with the hypothesized increase in the intrinsic coupling that arises from neural oscillatory phase alignment. Our results reveal distinct frequency bands exhibit altered power and coherence variations modulated by experience-driven plasticity.

Estimating Phase Amplitude Coupling between Neural Oscillations Based on Permutation and Entropy

Cross-frequency phase–amplitude coupling (PAC) plays an important role in neuronal oscillations network, reflecting the interaction between the phase of low-frequency oscillation (LFO) and amplitude of the high-frequency oscillations (HFO). Thus, we applied four methods based on permutation analysis to measure PAC, including multiscale permutation mutual information (MPMI), permutation conditional mutual information (PCMI), symbolic joint entropy (SJE), and weighted-permutation mutual information (WPMI). To verify the ability of these four algorithms, a performance test including the effects of coupling strength, signal-to-noise ratios (SNRs), and data length was evaluated by using simulation data. It was shown that the performance of SJE was similar to that of other approaches when measuring PAC strength, but the computational efficiency of SJE was the highest among all these four methods. Moreover, SJE can also accurately identify the PAC frequency range under the interference of spike noise. All in all, the results demonstrate that SJE is better for evaluating PAC between neural oscillations.

A novel beamformer-based imaging of phase–amplitude coupling (BIPAC) unveiling the inter-regional connectivity of emotional prosody processing in women with primary dysmenorrhea

Objective. Neural communication or the interactions of brain regions play a key role in the formation of functional neural networks. A type of neural communication can be measured in the form of phase–amplitude coupling (PAC), which is the coupling between the phase of low-frequency oscillations and the amplitude of high-frequency oscillations. This paper presents a beamformer-based imaging method, beamformer-based imaging of PAC (BIPAC), to quantify the strength of PAC between a seed region and other brain regions. Approach. A dipole is used to model the ensemble of neural activity within a group of nearby neurons and represents a mixture of multiple source components of cortical activity. From ensemble activity at each brain location, the source component with the strongest coupling to the seed activity is extracted, while unrelated components are suppressed to enhance the sensitivity of coupled-source estimation. Main results. In evaluations using simulation data sets, BIPAC proved advantageous with regard to estimation accuracy in source localization, orientation, and coupling strength. BIPAC was also applied to the analysis of magnetoencephalographic signals recorded from women with primary dysmenorrhea in an implicit emotional prosody experiment. In response to negative emotional prosody, auditory areas revealed strong PAC with the ventral auditory stream and occipitoparietal areas in the theta–gamma and alpha–gamma bands, which may respectively indicate the recruitment of auditory sensory memory and attention reorientation. Moreover, patients with more severe pain experience appeared to have stronger coupling between auditory areas and temporoparietal regions. Significance. Our findings indicate that the implicit processing of emotional prosody is altered by menstrual pain experience. The proposed BIPAC is feasible and applicable to imaging inter-regional connectivity based on cross-frequency coupling estimates. The experimental results also demonstrate that BIPAC is capable of revealing autonomous brain processing and neurodynamics, which are more subtle than active and attended task-driven processing.

Measuring Phase-Amplitude Coupling Based on the Jensen-Shannon Divergence and Correlation Matrix.

Phase-amplitude coupling (PAC) measures the relationship between the phase of low-frequency oscillations (LFO) and the amplitude of high-frequency oscillations (HFO). It plays an important functional role in neural information processing and cognition. Thus, we propose a novel method based on the Jensen-Shannon (JS) divergence and correlation matrix. The method takes the amplitude distributions of the HFO located in the corresponding phase bins of the LFO as multichannel inputs to construct a correlation matrix, where the elements are calculated based on the JS divergence between pairs of amplitude distributions. Then, the omega complexity extracted from the correlation matrix is used to estimate the PAC strength. The simulation results demonstrate that the proposed method can effectively reflect the PAC strength and slightly vary with the data length. Moreover, it outperforms five frequently used algorithms in the performance against additive white Gaussian noise and spike noise and the ability of detecting PAC in wide frequency ranges. To validate our proposed method with real data, it was applied to analyze the local field potential recorded from the dorsomedial striatum in a male Sprague-Dawley rat. It can replicate previous results obtained with other PAC metrics. In conclusion, these results suggest that our proposed method is a powerful tool for measuring the PAC between neural oscillations.

Spatial Attention and Temporal Expectation Exert Differential Effects on Visual and Auditory Discrimination.

Anticipation of an impending stimulus shapes the state of the sensory systems, optimizing neural and behavioral responses. Here, we studied the role of brain oscillations in mediating spatial and temporal anticipations. Because spatial attention and temporal expectation are often associated with visual and auditory processing, respectively, we directly contrasted the visual and auditory modalities and asked whether these anticipatory mechanisms are similar in both domains. We recorded the magnetoencephalogram in healthy human participants performing an auditory and visual target discrimination task, in which cross-modal cues provided both temporal and spatial information with regard to upcoming stimulus presentation. Motivated by prior findings, we were specifically interested in delta (1-3 Hz) and alpha (8-13 Hz) band oscillatory state in anticipation of target presentation and their impact on task performance. Our findings support the view that spatial attention has a stronger effect in the visual domain, whereas temporal expectation effects are more prominent in the auditory domain. For the spatial attention manipulation, we found a typical pattern of alpha lateralization in the visual system, which correlated with response speed. Providing a rhythmic temporal cue led to increased postcue synchronization of low-frequency rhythms, although this effect was more broadband in nature, suggesting a general phase reset rather than frequency-specific neural entrainment. In addition, we observed delta-band synchronization with a frontal topography, which correlated with performance, especially in the auditory task. Combined, these findings suggest that spatial and temporal anticipations operate via a top-down modulation of the power and phase of low-frequency oscillations, respectively.

Comparison of Wavelet and RID-Rihaczek Based Methods for Phase-Amplitude Coupling

Oscillatory phenomena and linear/nonlinear interactions across different oscillatory frequencies are commonly seen between the elements of complex systems. One particular form of interaction that is widely encountered is the modulation of the amplitude of broadband high-frequency oscillations by the phase of low-frequency oscillations, defined as phase-amplitude coupling (PAC). Conventional methods for assessing PAC mostly rely on the Hilbert transform. Previous studies have shown that this method produces biased or spurious PAC estimates as it is highly dependent on the parameters of the bandpass filter used to extract narrowband signals from broadband signals. Recently, wavelet-based methods have been proposed to address some of these limitations. In this letter, we provide a thorough comparison between wavelet-based PAC measures and our recently introduced Reduced Interference Rihaczek (RID-Rihaczek) distribution based PAC both analytically and through simulations. The proposed method is shown to yield higher frequency resolution PAC estimates compared to wavelet-based methods.

Time-Frequency Based Phase-Amplitude Coupling Measure For Neuronal Oscillations

Oscillatory activity in the brain has been associated with a wide variety of cognitive processes including decision making, feedback processing, and working memory. The high temporal resolution provided by electroencephalography (EEG) enables the study of variation of oscillatory power and coupling across time. Various forms of neural synchrony across frequency bands have been suggested as the mechanism underlying neural binding. Recently, a considerable amount of work has focused on phase-amplitude coupling (PAC)– a form of cross-frequency coupling where the amplitude of a high frequency signal is modulated by the phase of low frequency oscillations. The existing methods for assessing PAC have some limitations including limited frequency resolution and sensitivity to noise, data length and sampling rate due to the inherent dependence on bandpass filtering. In this paper, we propose a new time-frequency based PAC (t-f PAC) measure that can address these issues. The proposed method relies on a complex time-frequency distribution, known as the Reduced Interference Distribution (RID)-Rihaczek distribution, to estimate both the phase and the envelope of low and high frequency oscillations, respectively. As such, it does not rely on bandpass filtering and possesses some of the desirable properties of time-frequency distributions such as high frequency resolution. The proposed technique is first evaluated for simulated data and then applied to an EEG speeded reaction task dataset. The results illustrate that the proposed time-frequency based PAC is more robust to varying signal parameters and provides a more accurate measure of coupling strength.

Human olfactory-auditory integration requires phase synchrony between sensory cortices

Multisensory integration is particularly important in the human olfactory system, which is highly dependent on non-olfactory cues, yet its underlying neural mechanisms are not well understood. In this study, we use intracranial electroencephalography techniques to record neural activity in auditory and olfactory cortices during an auditory-olfactory matching task. Spoken cues evoke phase locking between low frequency oscillations in auditory and olfactory cortices prior to odor arrival. This phase synchrony occurs only when the participant’s later response is correct. Furthermore, the phase of low frequency oscillations in both auditory and olfactory cortical areas couples to the amplitude of high-frequency oscillations in olfactory cortex during correct trials. These findings suggest that phase synchrony is a fundamental mechanism for integrating cross-modal odor processing and highlight an important role for primary olfactory cortical areas in multisensory integration with the olfactory system.

The Effects of Transcranial Alternating Current Stimulation on the Auditory Steady-State Response and its Association with Schizotypy

Background: Evidence for impaired neural oscillations associated with particular circuits in schizophrenia (e.g. gamma oscillations [30 to 100 Hz]) has been found in the observations of reduced amplitude and phase locking factor (PLF) aspects of the 40-Hz auditory steady-state response (ASSR). As both amplitude and PFL of the 40-Hz ASSR are associated with a particular phase of low frequency oscillations, we examined in healthy control subjects the acute effects of low (theta) and high frequency (gamma) transcranial alternating current stimulation (tACS) on the 40-Hz response and its relation to schizotypy.

Identifying Phase-Amplitude Coupling in Cyclic Alternating Pattern using Masking Signals

Judiciously classifying phase-A subtypes in cyclic alternating pattern (CAP) is critical for investigating sleep dynamics. Phase-amplitude coupling (PAC), one of the representative forms of neural rhythmic interaction, is defined as the amplitude of high-frequency activities modulated by the phase of low-frequency oscillations. To examine PACs under more or less synchronized conditions, we propose a nonlinear approach, named the masking phase-amplitude coupling (MPAC), to quantify physiological interactions between high (α/lowβ) and low (δ) frequency bands. The results reveal that the coupling intensity is generally the highest in subtype A1 and lowest in A3. MPACs among various physiological conditions/disorders (p < 0.0001) and sleep stages (p < 0.0001 except S4) are tested. MPACs are found significantly stronger in light sleep than deep sleep (p < 0.0001). Physiological conditions/disorders show similar order in MPACs. Phase-amplitude dependence between δ and α/lowβ oscillations are examined as well. δ phase tent to phase-locked to α/lowβ amplitude in subtype A1 more than the rest. These results suggest that an elevated δ-α/lowβ MPACs can reflect some synchronization in CAP. Therefore, MPAC can be a potential tool to investigate neural interactions between different time scales, and δ-α/lowβ MPAC can serve as a feasible biomarker for sleep microstructure.

Prestimulus EEG Power Predicts Conscious Awareness But Not Objective Visual Performance.

Prestimulus oscillatory neural activity has been linked to perceptual outcomes during performance of psychophysical detection and discrimination tasks. Specifically, the power and phase of low frequency oscillations have been found to predict whether an upcoming weak visual target will be detected or not. However, the mechanisms by which baseline oscillatory activity influences perception remain unclear. Recent studies suggest that the frequently reported negative relationship between α power and stimulus detection may be explained by changes in detection criterion (i.e., increased target present responses regardless of whether the target was present/absent) driven by the state of neural excitability, rather than changes in visual sensitivity (i.e., more veridical percepts). Here, we recorded EEG while human participants performed a luminance discrimination task on perithreshold stimuli in combination with single-trial ratings of perceptual awareness. Our aim was to investigate whether the power and/or phase of prestimulus oscillatory activity predict discrimination accuracy and/or perceptual awareness on a trial-by-trial basis. Prestimulus power (3–28 Hz) was inversely related to perceptual awareness ratings (i.e., higher ratings in states of low prestimulus power/high excitability) but did not predict discrimination accuracy. In contrast, prestimulus oscillatory phase did not predict awareness ratings or accuracy in any frequency band. These results provide evidence that prestimulus α power influences the level of subjective awareness of threshold visual stimuli but does not influence visual sensitivity when a decision has to be made regarding stimulus features. Hence, we find a clear dissociation between the influence of ongoing neural activity on conscious awareness and objective performance.

The Detection of Phase Amplitude Coupling during Sensory Processing.

There is increasing interest in understanding how the phase and amplitude of distinct neural oscillations might interact to support dynamic communication within the brain. In particular, previous work has demonstrated a coupling between the phase of low frequency oscillations and the amplitude (or power) of high frequency oscillations during certain tasks, termed phase amplitude coupling (PAC). For instance, during visual processing in humans, PAC has been reliably observed between ongoing alpha (8–13 Hz) and gamma-band (>40 Hz) activity. However, the application of PAC metrics to electrophysiological data can be challenging due to numerous methodological issues and lack of coherent approaches within the field. Therefore, in this article we outline the various analysis steps involved in detecting PAC, using an openly available MEG dataset from 16 participants performing an interactive visual task. Firstly, we localized gamma and alpha-band power using the Fieldtrip toolbox, and extracted time courses from area V1, defined using a multimodal parcelation scheme. These V1 responses were analyzed for changes in alpha-gamma PAC, using four common algorithms. Results showed an increase in alpha (7–13 Hz)–gamma (40–100 Hz) PAC in response to the visual grating stimulus, though specific patterns of coupling were somewhat dependent upon the algorithm employed. Additionally, post-hoc analyses showed that these results were not driven by the presence of non-sinusoidal oscillations, and that trial length was sufficient to obtain reliable PAC estimates. Finally, throughout the article, methodological issues and practical guidelines for ongoing PAC research will be discussed.

Temporal-spatial characteristics of phase-amplitude coupling in electrocorticogram for human temporal lobe epilepsy.

Neural activity of the epileptic human brain contains low- and high-frequency oscillations in different frequency bands, some of which have been used as reliable biomarkers of the epileptogenic brain areas. However, the relationship between the low- and high-frequency oscillations in different cortical areas during the period from pre-seizure to post-seizure has not been completely clarified. We recorded electrocorticogram data from the temporal lobe and hippocampus of seven patients with temporal lobe epilepsy. The modulation index based on the Kullback-Leibler distance and the phase-amplitude coupling co-modulogram were adopted to quantify the coupling strength between the phase of low-frequency oscillations (0.2-10Hz) and the amplitude of high-frequency oscillations (11-400Hz) in different seizure epochs. The time-varying phase-amplitude modulogram was used to analyze the phase-amplitude coupling pattern during the entire period from pre-seizure to post-seizure in both the left and right temporal lobe and hippocampus. Channels with strong modulation index were compared with the seizure onset channels identified by the neurosurgeons and the resection channels in the clinical surgery. The phase-amplitude coupling strength (modulation index) increased significantly in the mid-seizure epoch and decrease significantly in seizure termination and post-seizure epochs (p<0.001). The strong phase-amplitude-modulating low- and high-frequency oscillations in the mid-seizure epoch were mainly δ, θ, and α oscillations and γ and ripple oscillations, respectively. The phase-amplitude modulation and strength varied among channels and was asymmetrical in the left and right temporal cortex and hippocampus. The "fall-max" phase-amplitude modulation pattern, i.e., high-frequency amplitudes were largest in the low-frequency phase range [-π, 0], which corresponded to the falling edges of low-frequency oscillations, appeared in the middle period of the seizures at epileptic focus channels. Channels with strong modulation index appeared on the corresponding left or right temporal cortex of surgical resection and overlapped with the clinical resection zones in all patients. The "fall-max" pattern between the phase of low-frequency oscillation and amplitude of high-frequency oscillation that appeared in the middle period of the seizures is a reliable biomarker in epileptogenic cortical areas. The modulation index can be used as a good tool for lateralization and localization for the epileptic focus in patients with epilepsy. Phase-amplitude coupling can provide meaningful reference for accurate resection of epileptogenic focus and provide insight into the underlying neural dynamics of the epileptic seizure in patients with temporal lobe epilepsy.

High-frequency neural activity predicts word parsing in ambiguous speech streams.

During speech listening, the brain parses a continuous acoustic stream of information into computational units (e.g., syllables or words) necessary for speech comprehension. Recent neuroscientific hypotheses have proposed that neural oscillations contribute to speech parsing, but whether they do so on the basis of acoustic cues (bottom-up acoustic parsing) or as a function of available linguistic representations (top-down linguistic parsing) is unknown. In this magnetoencephalography study, we contrasted acoustic and linguistic parsing using bistable speech sequences. While listening to the speech sequences, participants were asked to maintain one of the two possible speech percepts through volitional control. We predicted that the tracking of speech dynamics by neural oscillations would not only follow the acoustic properties but also shift in time according to the participant's conscious speech percept. Our results show that the latency of high-frequency activity (specifically, beta and gamma bands) varied as a function of the perceptual report. In contrast, the phase of low-frequency oscillations was not strongly affected by top-down control. Whereas changes in low-frequency neural oscillations were compatible with the encoding of prelexical segmentation cues, high-frequency activity specifically informed on an individual's conscious speech percept.

Movement-related dynamics of cortical oscillations in Parkinson's disease and essential tremor.

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.

Untangling Cortico-Striatal Connectivity and Cross-Frequency Coupling in L-DOPA-Induced Dyskinesia.

We simultaneously recorded local field potentials (LFPs) in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analyzed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80-Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the control state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients

Objective. Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs). Methods. Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase–amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5–4 Hz) and theta- (4–8 Hz) modulation of HFOs (30–450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed. Main results. MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected tissue suggesting that the resected tissue was not appropriate, which was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel Class I patient. Significance. LFO-modulated HFOs can be used to identify ROIs in extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more accurate localization of the EZ. These ROIs may result in better surgical outcomes when used to compliment the SOZs identified by clinicians for resection.