Phase Resetting Research Articles

Entrainment of somatosensory beta and gamma oscillations accompany improvement in tactile acuity after periodic and aperiodic repetitive sensory stimulation

Previous research showed that repetitive sensory stimulation entrains neural oscillations at the stimulation rate, facilitates long-term potentiation like perceptual learning, and improves behavioural performance. For example, short-time repetitive tactile stimulation improved tactile acuity measured with two-point or spatial orientation discrimination tests. The behavioural gain was maximal for a stimulation rate of 20 Hz, the same frequency at which repetitive somatosensory stimulation elicits a steady-state response with maximum amplitude. The current study investigated whether sensory stimulation must be strictly periodic to induce perceptual learning and whether the 20-Hz steady-state response plays a crucial role in the neural mechanisms of perceptual learning. In a crossover-designed experiment, young, healthy adults received sensory stimulation to the fingertip on three subsequent days. The stimulation was either periodic or temporally randomized (aperiodic) with the same number of stimuli. Tactile acuity was assessed with a grating orientation discrimination task, and brain activity was measured with magnetoencephalography (MEG). Stimulus type-by-session interactions were found for behavioural and brain data. Tactile acuity improved more after a session with aperiodic than periodic stimulation. Beta-band 20-Hz steady-state responses were localized in the primary somatosensory cortex contralateral to the stimulated finger and had larger amplitudes after periodic than aperiodic stimulation. Both stimulus types also elicited gamma oscillations, which increased in amplitude more with aperiodic than periodic stimulation. Sensory stimuli caused a phase reset of sensorimotor beta oscillations phase-coupled to alpha oscillations. The system of stimulus-related oscillations was discussed as underlying temporal processing. Learning may result from facilitating the temporal code. More pronounced behavioural gain with aperiodic than periodic stimulation suggests beneficial effects of temporal stimulus variability for perceptual learning.

Prelimbic cortex drives discrimination of non-aversion via amygdala somatostatin interneurons

The amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate discrimination of a non-threatening stimulus is unknown. Here, we show that somatostatin (SOM) interneurons in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues and desynchronize cell firing by blocking phase reset of theta oscillations during the safe cue. Furthermore, we show that SOM activation and desynchronization of the BLA is PL-dependent and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.

Neural dynamics driving audio-visual integration in autism.

Audio-visual (AV) integration plays a crucial role in supporting social functions and communication in autism spectrum disorder (ASD). However, behavioral findings remain mixed and, importantly, little is known about the underlying neurophysiological bases. Studies in neurotypical adults indicate that oscillatory brain activity in different frequencies subserves AV integration, pointing to a central role of (i) individual alpha frequency (IAF), which would determine the width of the cross-modal binding window; (ii) pre-/peri-stimulus theta oscillations, which would reflect the expectation of AV co-occurrence; (iii) post-stimulus oscillatory phase reset, which would temporally align the different unisensory signals. Here, we investigate the neural correlates of AV integration in children with ASD and typically developing (TD) peers, measuring electroencephalography during resting state and in an AV integration paradigm. As for neurotypical adults, AV integration dynamics in TD children could be predicted by the IAF measured at rest and by a modulation of anticipatory theta oscillations at single-trial level. Conversely, in ASD participants, AV integration/segregation was driven exclusively by the neural processing of the auditory stimulus and the consequent auditory-induced phase reset in visual regions, suggesting that a disproportionate elaboration of the auditory input could be the main factor characterizing atypical AV integration in autism.

Neural entrainment via perceptual inferences.

Entrainment depends on sequential neural phase reset by regular stimulus onset, a temporal parameter. Entraining to sequences of identical stimuli also entails stimulus feature predictability, but this component is not readily separable from temporal regularity. To test if spectral regularities concur with temporal regularities in determining the strength of auditory entrainment, we devised sound sequences that varied in conditional perceptual inferences based on deviant sound repetition probability: strong inference (100% repetition probability: If a deviant appears, then it will repeat), weak inference (75% repetition probability) and no inference (50%: A deviant may or may not repeat with equal probability). We recorded EEG data from 15 young human participants pre-attentively listening to the experimental sound sequences delivered either isochronously or anisochronously (±20% jitter), at both delta (1.67 Hz) and theta (6.67 Hz) stimulation rates. Strong perceptual inferences significantly enhanced entrainment at either stimulation rate and determined positive correlations between precision in phase distribution at the onset of deviant trials and entrained power. We conclude that both spectral predictability and temporal regularity govern entrainment via neural phase control.

A 6.15–10.9 Gb/s 0.58 pJ/Bit Reference-Less Half-Rate Clock and Data Recovery With “Phase Reset” Scheme

This paper presents a low power injection-locked oscillator (ILO)-type clock and data recovery (CDR) in 40 nm CMOS. An efficient ``phase reset'' scheme is proposed to periodically realign the clock phase to the rising edge of data. The frequency information is extracted by comparing the rising edge of the data and the clock after aligning the phase using a bang-bang phase detector (BBPD). Additionally, a low power injection-locked two-stage ring digitally controlled oscillator (ILDCO) is employed to provide four-phase quadrature clock and significantly reduce the power consumption. Based on the proposed architecture, the fabricated CDR consumes only 5.8 mW from a 0.9 V supply, while being able to extract the clock signal from 6.15 to 10.9 Gb/s input data with a measured jitter tolerance (JTOL) of 0.15 UIpp at the highest frequency, indicating that the CDR meets the OC-192 mask. Furthermore, the proposed CDR demonstrates a substantial improvement in the power efficiency of 0.58 pJ/bit.

Modeling (circadian).

In this chapter, we will discuss mathematical models of the master circadian rhythm in the suprachiasmatic nucleus of the hypothalamus with a particular emphasis on models that incorporate the effect of light on circadian phase resetting and melatonin suppression. We will show that limit cycle oscillators provide a better representation of the salient properties of the human circadian system than a sinusoid. We will then discuss how the phototransduction of light to the SCN has been incorporated in various models. Finally, we will introduce different theoretical and practical applications of these models and highlight areas for future model development.

Systematic review of drugs that modify the circadian system's phase-shifting responses to light exposure.

We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.

Reaction-Diffusion Dynamics of pH Oscillators in Oscillatory Forced Open Spatial Reactors.

Studying the effect of coupling and forcing of oscillators is a significant area of interest within nonlinear dynamics and has provided evidence of many interesting phenomena, such as synchronization, beating, oscillatory death, and phase resetting. Many studies have also reported along this line in reaction–diffusion systems, which are preferably explored experimentally by using open reactors. These reactors consist of one or two homogeneous (well-stirred) tanks, which provide the boundary conditions for a spatially distributed part. The spatiotemporal dynamics of this configuration in the presence of temporal oscillations in the homogeneous part has not been systematically investigated. This paper aims to explore numerically the effect of time-periodic boundary conditions on the dynamics of open reactors provided by autonomous and forced oscillations in the well-stirred part. A simple model of pH oscillators can produce various phenomena under these conditions, for example, superposition and modulation of spatiotemporal oscillations and forced bursting. The autonomous oscillatory boundary conditions can be generated by the same kinetic instabilities that result in spatiotemporal oscillations in the spatially distributed part. The forced oscillations are induced by sinusoidal modulation on the inflow concentration of the activator in the tank. The simulations confirmed that this type of forcing is more effective when the modulation period is longer than the residence time of the well-stirred part. The use of time-periodic boundary conditions may open a new perspective in the control and design of spatiotemporal phenomena in open one-side-fed and two-side-fed reactors.

Detecting attention-related rhythms: When is behavior not enough? (Commentary on van der Werf et al. 2021).

Recent research suggests that environmental sampling is a fundamentally rhythmic process (Benedetto, Morrone, & Tomassini, 2019; Fiebelkorn & Kastner, 2019; Schroeder, Wilson, Radman, Scharfman, & Lakatos, 2010). In primates, both attention-related sampling and exploratory eye movements are seemingly shaped by theta-band activity (3-8 Hz) in the large-scale network that directs both spatial attention and goal-directed eye movements (i.e., the 'attention network').

A state space modeling approach to real-time phase estimation.

Brain rhythms have been proposed to facilitate brain function, with an especially important role attributed to the phase of low-frequency rhythms. Understanding the role of phase in neural function requires interventions that perturb neural activity at a target phase, necessitating estimation of phase in real-time. Current methods for real-time phase estimation rely on bandpass filtering, which assumes narrowband signals and couples the signal and noise in the phase estimate, adding noise to the phase and impairing detections of relationships between phase and behavior. To address this, we propose a state space phase estimator for real-time tracking of phase. By tracking the analytic signal as a latent state, this framework avoids the requirement of bandpass filtering, separately models the signal and the noise, accounts for rhythmic confounds, and provides credible intervals for the phase estimate. We demonstrate in simulations that the state space phase estimator outperforms current state-of-the-art real-time methods in the contexts of common confounds such as broadband rhythms, phase resets, and co-occurring rhythms. Finally, we show applications of this approach to in vivo data. The method is available as a ready-to-use plug-in for the Open Ephys acquisition system, making it widely available for use in experiments.

Spermidine resets circadian clock phase in NIH3T3 cells.

Irregular light-dark cycles desynchronize the circadian clock via hormonal and neuronal pathways and increase the risk of various diseases. This study demonstrated that a single pulse of spermidine-a polyamine-strongly induced circadian phase advances in the presence or absence of dexamethasone (a synthetic glucocorticoid) in NIH3T3 cells transfected with the Bmal1 promotor-driven luciferase reporter gene. The spermidine-induced phase advances were 2-3 fold greater than were the dexamethasone-induced shifts. The phase resetting effect of spermidine occurred in a dose- and time-dependent manner and was not blocked by RU486, an antagonist of glucocorticoid receptors. Spermidine treatment modulated the expression of clock genes within 60 min, which was sooner than changes in the expression of autophagy-related genes. These findings suggested that spermidine is a potent modulator of the circadian phase, acting through glucocorticoid receptor-independent pathways, and may be useful for treating diseases related to circadian desynchrony.

Generation of Direct-, Retrograde-, and Source-Wave Gaits in Multi-Legged Locomotion in a Decentralized Manner via Embodied Sensorimotor Interaction.

Multi-legged animals show several types of ipsilateral interlimb coordination. Millipedes use a direct-wave gait, in which the swing leg movements propagate from posterior to anterior. In contrast, centipedes use a retrograde-wave gait, in which the swing leg movements propagate from anterior to posterior. Interestingly, when millipedes walk in a specific way, both direct and retrograde waves of the swing leg movements appear with the waves' source, which we call the source-wave gait. However, the gait generation mechanism is still unclear because of the complex nature of the interaction between neural control and dynamic body systems. The present study used a simple model to understand the mechanism better, primarily how local sensory feedback affects multi-legged locomotion. The model comprises a multi-legged body and its locomotion control system using biologically inspired oscillators with local sensory feedback, phase resetting. Each oscillator controls each leg independently. Our simulation produced the above three types of animal gaits. These gaits are not predesigned but emerge through the interaction between the neural control and dynamic body systems through sensory feedback (embodied sensorimotor interaction) in a decentralized manner. The analytical description of these gaits' solution and stability clarifies the embodied sensorimotor interaction's functional roles in the interlimb coordination.

Neural activity in the human anterior thalamus during natural vision

In natural vision humans and other primates explore environment by active sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and in the medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brain’s circuitry that is modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using recordings in the human thalamus of three surgical patients during natural vision, we found that saccades and visual stimulus onset both modulate neural activity, but with distinct field potential morphologies. Specifically, we found that fixation-locked field potentials had a component that preceded saccade onset. It was followed by an early negativity around 50 ms after fixation onset which is significantly faster than any response to visual stimulus presentation. The timing of these events suggests that the ANT is predictively modulated before the saccadic eye movement. We also found oscillatory phase concentration, peaking at 3–4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80–180 Hz), both locked to fixation onset supporting the idea that neural oscillations in these nuclei are reorganized to a low excitability state right after fixation onset. These findings show that during real-world natural visual exploration neural dynamics in the human ANT is influenced by visual and oculomotor events, which supports the idea that ANT, apart from their contribution to episodic memory, also play a role in natural vision.

Phase Resetting in the Anterior Cingulate Cortex Subserves Childhood Attention and Is Impaired by Epilepsy.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8hours sleep at night, four meals during a 16hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n=16 males, mean age±SD=23.4±2.3years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n=25, 14 females, 36.3±8.9years) across four protocols; two with abrupt 8hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8hour advance (1.6hours/day over 5days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7hours and -4.2hours, respectively, compared to -6.6hours and -4.7hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1hours) but not the gradual (+2.1hours) protocol, compared to +3.1hours and +2.8hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

A neurobiologically inspired mapping and navigating framework for mobile robots

To improve the cognitive ability of the mobile robot in an unknown environment, this paper proposes an episodic memory based self-organizing learning (EM-SOL) framework for robotic experiences learning, cognitive map building and navigation. This EM-SOL framework uses the spatial cells in the hippocampus and entorhinal cortex to path integrate the robotic kinesthetic cues for dead reckoning, and meanwhile extracts the visual cues to activate state neurons for state recognition. By updating the state neurons network, this framework constructs the robotic episodic memory to store these particular experiences created along the exploration process, and achieves the robotic self-organizing learning. The framework based map building method can optimize the cumulative error by introducing the spatial cells phase reset mechanism, and build an episodic-cognitive map that describes not only the topology relationship but also the cognition relationship between these particular experiences in the environment. Furthermore, a combined topological and metric vector navigation method is presented, which can locate the robot relative to its previous experiences in the memory space, anticipate a preferred global path to the target, and guide the mobile robot to navigate to the target accurately. Finally, the proposed EM-SOL framework based methods are evaluated in both the physical environments and the standard KITTI dataset. The results show that the mobile robot can keep on learning to adapt to the changes in an unknown environment, construct valid episodic memory to store these particular learned experiences, build an episodic-cognitive map and execute the target navigation task with high efficiency and accuracy.

Theta activity and phase resetting during perception of French homophonous utterances

ABSTRACT Speech perception involves segmenting a continuous stream of speech into its word components. This can be challenging in the case of homophonous utterances only differing in non-contrastive subphonemic features. Yet, the speech perception system seems able to discriminate subphonemic deviation in homophonous utterances, since it has been shown to elicit a mismatch response (MMN). Here, we focused on the oscillatory correlates, namely phase resetting and power, of non-contrastive subphonemic deviation processing in language. An oddball task that considered natural intraspeaker variability was used. Subphonemic deviance elicited intertrial phase coherence (ITC) differences in the theta band at Fz during the time window of the MMN. No differences in power were found. This suggests that the processing of subphonemic deviation in speech signals, reflected by the MMN, might rely on mechanisms of phase resetting. ITC might facilitate the synchronous firing of functional networks involved in the processing of subphonemic deviance.

Adaptive intensity transformation-based phase retrieval with high accuracy and fast convergence.

Phase-retrieval (PR) receivers can reconstruct complex-valued signals from two de-correlated intensity measurements, without the assistance of any optical carriers. However, both the calculation complexity with hundreds of iterations and the limited PR accuracy prevent it from being applied to high-speed photonic interconnections. Here we propose and demonstrate a PR receiver based on adaptive intensity transformation, with the capability of both fast convergence and high accuracy. Then we numerically reconstruct 56 GBaud QPSK signals after the 80 km standard single-mode fiber transmission by using our proposed PR receiver with only 50 iterations. In comparison with the recently reported PR receiver with the phase reset, our proposed PR receiver can reduce the required optical signal-to-noise ratio by 1.95 and 1.89 dB, in terms of 20% soft-decision and 7% hard-decision forward-error correction, respectively.

Prefrontal Theta-Phase Synchronized Brain Stimulation With Real-Time EEG-Triggered TMS

BackgroundTheta-band neuronal oscillations in the prefrontal cortex are associated with several cognitive functions. Oscillatory phase is an important correlate of excitability and phase synchrony mediates information transfer between neuronal populations oscillating at that frequency. The ability to extract and exploit the prefrontal theta rhythm in real time in humans would facilitate insight into neurophysiological mechanisms of cognitive processes involving the prefrontal cortex, and development of brain-state-dependent stimulation for therapeutic applications.ObjectivesWe investigate individual source-space beamforming-based estimation of the prefrontal theta oscillation as a method to target specific phases of the ongoing theta oscillations in the human dorsomedial prefrontal cortex (DMPFC) with real-time EEG-triggered transcranial magnetic stimulation (TMS). Different spatial filters for extracting the prefrontal theta oscillation from EEG signals are compared and additional signal quality criteria are assessed to take into account the dynamics of this cortical oscillation.MethodsTwenty two healthy participants were recruited for anatomical MRI scans and EEG recordings with 18 composing the final analysis. We calculated individual spatial filters based on EEG beamforming in source space. The extracted EEG signal was then used to simulate real-time phase-detection and quantify the accuracy as compared to post-hoc phase estimates. Different spatial filters and triggering parameters were compared. Finally, we validated the feasibility of this approach by actual real-time triggering of TMS pulses at different phases of the prefrontal theta oscillation.ResultsHigher phase-detection accuracy was achieved using individualized source-based spatial filters, as compared to an average or standard Laplacian filter, and also by detecting and avoiding periods of low theta amplitude and periods containing a phase reset. Using optimized parameters, prefrontal theta-phase synchronized TMS of DMPFC was achieved with an accuracy of ±55°.ConclusionThis study demonstrates the feasibility of triggering TMS pulses during different phases of the ongoing prefrontal theta oscillation in real time. This method is relevant for brain state-dependent stimulation in human studies of cognition. It will also enable new personalized therapeutic repetitive TMS protocols for more effective treatment of neuropsychiatric disorders.

Frequency-dependent effects of EEG phase resetting on reaction time

There is trial-to-trial variability in the reaction time to stimulus presentation. Since this variability exists even in an identical stimulus condition, it reflects the internal neural dynamics of the brain. To understand the neural dynamics that influence the reaction time, we conducted an electroencephalogram (EEG) experiment in which participants were asked to press a response button as quickly as possible when a stimulus was visually presented. Phase-locking factor analysis revealed that phase resetting in two frequency bands, which appeared 0.2 s after the stimulus presentation, characterized the reaction time. The combination of the theta band phase resetting in the left parietal region and the delta band phase resetting mainly in the posterior region was associated with the fastest reaction time, whereas delta band phase resetting without theta band phase resetting was associated with the faster reaction time. The results indicated that there were frequency-dependent effects in the relationships between the EEG phase resetting and reaction time.