Strong Phase-amplitude Coupling Research Articles

Aberrant Cortical Activity in 5xFAD Mice in Response to Social and Non-Social Olfactory Stimuli.

Neuroimaging studies investigating the behavioral and psychological symptoms of dementia (BPSD)- such as apathy, anxiety, and depression- have linked some of these symptoms with altered neural activity. However, inconsistencies in operational definitions and rating scales, limited scope of assessments, and poor temporal resolution of imaging techniques have hampered human studies. Many transgenic (Tg) mouse models of Alzheimer's disease (AD) exhibit BPSD-like behaviors concomitant with AD-related neuropathology, allowing examination of how neural activity may relate to BPSD-like behaviors with high temporal and spatial resolution. To examine task-dependent neural activity in the medial prefrontal cortex (mPFC) of AD-model mice in response to social and non-social olfactory stimuli. We previously demonstrated age-related decreases in social investigation in Tg 5xFAD females, and this reduced social investigation is evident in Tg 5xFAD females and males by 6 months of age. In the present study, we examine local field potential (LFP) in the mPFC of awake, behaving 5xFAD females and males at 6 months of age during exposure to social and non-social odor stimuli in a novel olfactometer. Our results indicate that Tg 5xFAD mice exhibit aberrant baseline and task-dependent LFP activity in the mPFC- including higher relative delta (1-4 Hz) band power and lower relative power in higher bands, and overall stronger phase-amplitude coupling- compared to wild-type controls. These results are consistent with previous human and animal studies examining emotional processing, anxiety, fear behaviors, and stress responses, and suggest that Tg 5xFAD mice may exhibit altered arousal or anxiety.

Estimating the Frequencies of Maximal Theta-Gamma Coupling in EEG during the N-Back Task: Sensitivity to Methodology and Temporal Instability

Phase-amplitude coupling (PAC) of theta and gamma rhythms of the brain has been observed in animals and humans, with evidence of its involvement in cognitive functions and brain disorders. This motivates finding individual frequencies of maximal theta-gamma coupling (TGC) and using them to adjust brain stimulation. This use implies the stability of the frequencies at least during the investigation, which has not been sufficiently studied. Meanwhile, there is a range of available algorithms for PAC estimation in the literature. We explored several options at different steps of the calculation, applying the resulting algorithms to the EEG data of 16 healthy subjects performing the n-back working memory task, as well as a benchmark recording with previously reported strong PAC. By comparing the results for the two halves of each session, we estimated reproducibility at a time scale of a few minutes. For the benchmark data, the results were largely similar between the algorithms and stable over time. However, for the EEG, the results depended substantially on the algorithm, while also showing poor reproducibility, challenging the validity of using them for personalizing brain stimulation. Further research is needed on the PAC estimation algorithms, cognitive tasks, and other aspects to reliably determine and effectively use TGC parameters in neuromodulation.

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.

Hippocampal CA1 and cortical interictal oscillations in the pilocarpine model of epilepsy

Quantitative electroencephalogram analysis has been increasingly applied to study fine changes in brain oscillations in epilepsy. Here we aimed to evaluate interictal oscillations using pilocarpine model of epilepsy to identify changes in network synchronization. We analyzed the in vivo local field potential of two cortical layers (Ctx1, Ctx2) and hippocampal CA1 (stratum oriens-Ors, pyramidale-Pyr, radiatum-Rad and lacunosum-moleculare-LM) in rats, about 5 weeks after pilocarpine injection. Animals that had status epilepticus (SE) and later spontaneous recurrent seizures (SRS) (epileptic animals) exhibited higher delta power recorded in cortical and hippocampal Ors, Rad and LM electrodes. They also had lower power of theta in Ctx1, Ctx2, Ors and LM, lower slow gamma in Ctx1, Ctx2 and Ors, and lower middle and fast gamma power in Ors. NSE animals had higher delta and lower slow gamma power in Ctx1 only, and lower theta power in Ctx1, Ctx2 and LM. Essentially, epileptic animals had higher delta coherence between Ctx1-Ors, Ctx2-Ors, Ctx2-Pyr, Pyr-Ors and stronger phase-amplitude coupling (PAC) between delta and all frequencies in Rad. NSE animals, also had higher delta coherence between Ctx1-Ors and Ctx2-Ors with no changes in PAC, suggesting some cortical network reorganization. Our data suggest an increased synchrony in cortex and CA1 of epileptic animals, particularly for delta frequency with intense delta coupling in Rad, probably an important synchronization site. Understanding the rhythms organization at non-ictal state could provide insights about network connectivity involved in ictogenesis and seizure propagation.

Measuring transient phase-amplitude coupling using local mutual information

Here we demonstrate the suitability of a local mutual information measure for estimating the temporal dynamics of cross-frequency coupling (CFC) in brain electrophysiological signals. In CFC, concurrent activity streams in different frequency ranges interact and transiently couple. A particular form of CFC, phase-amplitude coupling (PAC), has raised interest given the growing amount of evidence of its possible role in healthy and pathological brain information processing. Although several methods have been proposed for PAC estimation, only a few have addressed the estimation of the temporal evolution of PAC, and these typically require a large number of experimental trials to return a reliable estimate. Here we explore the use of mutual information to estimate a PAC measure (MIPAC) in both continuous and event-related multi-trial data. To validate these two applications of the proposed method, we first apply it to a set of simulated phase-amplitude modulated signals and show that MIPAC can successfully recover the temporal dynamics of the simulated coupling in either continuous or multi-trial data. Finally, to explore the use of MIPAC to analyze data from human event-related paradigms, we apply it to an actual event-related human electrocorticographic (ECoG) data set that exhibits strong PAC, demonstrating that the MIPAC estimator can be used to successfully characterize amplitude-modulation dynamics in electrophysiological data.

Phase-amplitude coupling and epileptogenesis in an animal model of mesial temporal lobe epilepsy

Polyrhythmic coupling of oscillatory components in electrophysiological signals results from the interactions between neuronal sub-populations within and between cell assemblies. Since the mechanisms underlying epileptic disorders should affect such interactions, abnormal level of cross-frequency coupling is expected to provide a signal marker of epileptogenesis. We measured phase-amplitude coupling (PAC), a form of cross-frequency coupling between neural oscillations, in a rodent model of mesial temporal lobe epilepsy. Sprague-Dawley rats (n = 4, 250–300 g) were injected with pilocarpine (380 mg/kg, i.p) to induce a status epilepticus (SE) that was stopped after 1 h with diazepam (5 mg/kg, s.c.) and ketamine (50 mg/kg, s.c.). Control animals (n = 6) did not receive any injection or treatment. Three days after SE, all animals were implanted with bipolar electrodes in the hippocampal CA3 subfield, entorhinal cortex, dentate gyrus and subiculum. Continuous video/EEG recordings were performed 24/7 at a sampling rate of 2 kHz, over 15 consecutive days. Pilocarpine-treated animals showed interictal spikes (5.25 (±2.5) per minute) and seizures (n = 32) that appeared 7 (±0.8) days after SE. We found that CA3 was the seizure onset zone in most epileptic animals, with stronger ongoing PAC coupling between seizures than in controls (Kruskal-Wallis test: chi2 (1,36) = 46.3, Bonferroni corrected, p < 0.001). Strong PAC in CA3 occurred between the phase of slow-wave oscillations (<1 Hz) and the amplitude of faster rhythms (50–180 Hz), with the strongest bouts of high-frequency activity occurring preferentially on the ascending phase of the slow wave. We also identified that cross-frequency coupling in CA3 (rho = 0.44, p < 0.001) and subiculum (rho = 0.41, p < 0.001) was positively correlated with the daily number of seizures. Overall, our study demonstrates that cross-frequency coupling may represent a signal marker in epilepsy and suggests that this methodology could be transferred to clinical scalp MEG and EEG recordings.

Detection of Epileptic Seizures Using Phase-Amplitude Coupling in Intracranial Electroencephalography.

Seizure detection using intracranial electroencephalography (iEEG) contributes to improved treatment of patients with refractory epilepsy. For that purpose, a feature of iEEG to characterize the ictal state with high specificity and sensitivity is necessary. We evaluated the use of phase–amplitude coupling (PAC) of iEEG signals over a period of 24 h to detect the ictal and interictal states. PAC was estimated by using a synchronisation index (SI) for iEEG signals from seven patients with refractory temporal lobe epilepsy. iEEG signals of the ictal state was characterised by a strong PAC between the phase of β and the amplitude of high γ. Furthermore, using SI values, the ictal state was successfully detected with significantly higher accuracy than by using the amplitude of high γ alone. In conclusion, PAC accurately distinguished the ictal state from the interictal state.

Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle.

Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7s on, 18s off) and standard cycle (30s on, 300s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8Hz) and high gamma (75-150Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy.

Phase-sensitive laser detection by frequency-shifted optical feedback

For further interferometric application on diffusive target, the phase fluctuation of a solid-state laser submitted to frequency shifted optical feedback is analyzed both theoretically and experimentally. As a drawback of the laser high sensitivity to optical feedback, the phase fluctuations induced by a strong phase-amplitude coupling noise are several orders of magnitude higher than the standard interferometric phase noise induced by the laser frequency width (Schawlow-Townes limit). Nevertheless, by sending a few milliwatts output power microchip laser beam on a diffusive target with an effective reflectivity of ${10}^{\ensuremath{-}9}$, a target displacement precision of $0.1\phantom{\rule{0.3em}{0ex}}\mathrm{\AA{}}∕\sqrt{\mathrm{Hz}}$ has been experimentally determined.

Linewidth of a semiconductor laser operating near threshold

The linewidth of a single-mode semiconductor laser operating in the threshold region has been studied both theoretically and experimentally. Due to strong phase-amplitude coupling in a semiconductor laser, its linewidth versus current characteristics exhibit a local minimum below threshold and a local maximum just about threshold. This implies a limitation in the minimum optical bandwidth achievable in a resonant-type semiconductor laser optical amplifier. The theoretical prediction has been verified experimentally on a conventional DFB semiconductor laser. >