Gamma Phase-amplitude Coupling Research Articles

Control of working memory by phase–amplitude coupling of human hippocampal neurons

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3–5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Functional interaction of abnormal beta and gamma oscillations on bradykinesia in parkinsonian rats

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson’s disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

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.

Transcranial magneto-acoustic stimulation improves spatial memory and modulates hippocampal neural oscillations in a mouse model of Alzheimer's disease.

In our study, we applied transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within a static magnetic field, in the APP/PS1 mouse model of Alzheimer's disease (AD) to explore the feasibility of TMAS on improving AD related spatial memory deficits and abnormal neural oscillations. The mice treated with TMAS once daily for 21 days. We recorded local field potential signals in the hippocampal CA1 region of the mice after TMAS treatment with in-vivo electrophysiology and evaluated the neural rehabilitative effect of TMAS with sharp-wave ripple (SWR), gamma oscillations during SWRs, and phase-amplitude coupling (PAC). The spatial memory function of the mice was examined by the Morris water maze (MWM) task. We found that TMAS improved the performance of MWM related spatial cognitive functions compared with AD group. Furthermore, our results implied that TMAS alleviated abnormalities in hippocampal SWRs, increased slow gamma power during SWRs, and promoted theta-slow gamma phase-amplitude coupling. These findings suggest that TMAS could have a positive influence on spatial memory through the modulation of neural oscillations. This work emphasizes the potential of TMAS to serve as a non-invasive method for Alzheimer's disease rehabilitation and promote the application of TMAS for the treatment of more neurological and brain aging diseases in the future.

Abnormally low sensorimotor α band nonlinearity serves as an effective EEG biomarker of Parkinson's disease.

Biomarkers obtained from the neurophysiological signals of patients with Parkinson's disease (PD) have objective value in assessing their motor condition for effective diagnosis, monitoring, and clinical intervention. Prominent cortical biomarkers of PD have typically been derived from various β band wave features. This study approached the topic from an alternative perspective and attempted to estimate a recently suggested measure representing α band nonlinear autocorrelative memory from a publicly available EEG dataset that involves 15 patients with earlier-stage PD (dopaminergic medication OFF and ON states) and 16 age-matched healthy controls. The cortical nonlinearity was elevated for the PD ON state compared with the OFF state for bilateral sensorimotor channels C3 and C4 (n = 26; P = 0.003). A similar statistical difference was also identified between PD OFF state and healthy subjects (n = 26; P = 0.049). Analysis over all channels revealed that the α band nonlinearity induced upon medication was constrained to sensorimotor regions. The α nonlinearity measure was compared with a well-accepted cortical biomarker of β-γ phase-amplitude coupling (PAC). They were in moderate negative correlation (r = -0.412; P = 0.036) for only healthy subjects, but not for the patients. The nonlinearity measure was found to be insusceptible to the nonstationary variations within the particular data. Our study provides further evidence that the α band nonlinearity measure can serve as a promising cortical biomarker of PD. The suggested measure can be estimated from a noninvasive low-resolution single scalp EEG channel of patients with relatively early-stage PD, who did not yet need to undergo deep brain stimulation operation.NEW & NOTEWORTHY This study suggests a nonlinearity measure that differentiates Parkinson's disease (PD) dopamine OFF-state scalp EEG data from those of dopamine ON-state patients and healthy subjects. Unlike typical PD cortical biomarkers based on β band activity, this metric shows elevation upon dopaminergic medication in the α band. We provide evidence supporting its potential as an early-stage promising PD biomarker that can be estimated from noninvasive EEG recordings with low resolution and SNR.

Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, and sevoflurane on sleep homeostasis in rats

BackgroundSleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. MethodsWe conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. ResultsDexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01). ConclusionsIn contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.

Neural Oscillation Disorder in the Hippocampal CA1 Region of Different Alzheimer's Disease Mice.

Alzheimer's disease (AD) is a well-known neurodegenerative disease that gradually induces neural network dysfunction and progressive memory deficits. Neural network activity is represented by rhythmic oscillations that influence local field potentials (LFPs). However, changes in hippocampal neural rhythmic oscillations in the early stage of AD remain largely unexplored. This study investigated neural rhythmic oscillations in 3-month-old APP/PS1 and 5x- FAD mice to assess early neural connectivity in AD. LFPs were recorded from the hippocampal CA1 region with implanted microelectrode arrays while the mice were in the awake resting stage. Welch fast Fourier transforms, continuous wavelet transforms, and phase-amplitude coupling analyses were used to compute the power density of different frequency bands and phase-amplitude modulation indices in the LFPs. Our results showed impaired theta, low gamma, and high gamma frequency band power in APP/PS1 and 5xFAD mice during the awake resting stage. AD mice also showed decreased delta, alpha, and beta frequency band power. Impaired theta-low gamma and theta-high gamma phaseamplitude coupling were observed in 5xFAD mice. This study revealed neural network activity differences in oscillation power and cross-frequency coupling in the early stage of AD, providing a new perspective for developing biomarkers for early AD diagnosis.

Increased theta-low gamma phase-amplitude coupling in resting electroencephalography after intermittent theta burst stimulation

ObjectiveIntermittent theta burst stimulation (iTBS) is based on the phase-amplitude coupling (PAC) pattern. We aimed to investigate the effect of iTBS on PAC in resting electroencephalography (EEG), which may provide insight into the underlying mechanism. MethodsTwenty-one healthy volunteers were recruited and received both active and sham neuroimaging-guided iTBS on two separate days, which was precisely delivered to the right superior temporal gyrus. On each experimental day, resting EEG was recorded before and after stimulation for each participant. PACs across electrodes and frequency bands were calculated and compared to investigate the effect of iTBS. ResultsTheta (4–6 Hz) -low gamma (45–55 Hz) PAC over the stimulation site had a significant interaction effect, which increased after the active iTBS but did not differ after the sham iTBS. No significant interaction effect occurred in other cross-frequency couplings such as delta-low gamma, alpha-low gamma, delta-high gamma, theta-high gamma, or alpha-high gamma PAC in the region of interest. ConclusioniTBS selectively modulated theta-low gamma PAC at the stimulation area, which exhibited both region- and frequency- specificity. This suggests that PAC may be a bridge connecting external neuromodulation to internal neuroplasticity.

Subjective cognitive decline exhibits alterations of resting-state phase-amplitude coupling in precuneus

ObjectiveSubjective cognitive decline (SCD) is associated with increased risks for progressing to Alzheimer’s disease (AD). This study aimed to investigate phase-amplitude coupling (PAC) in individuals with SCD and healthy controls (HCs) in the baseline year and determined the predictability of cognitive changes in the clinical follow-up. MethodsResting-state magnetoencephalographic signals in 29 HCs and 23 SCD subjects were recorded in the baseline year. The parahippocampal gyrus, posterior cingulate cortex and precuneus were selected as regions of interest (ROIs). Based on the grand-averaged comodulograms, delta–beta, delta–gamma and theta–gamma PAC values were extracted from each ROI. ResultsCompared with the HCs, the SCD group showed decreased theta–gamma PAC in the precuneus. Theta–gamma PAC of the left precuneus was associated with SCD severity and performance of immediate recall in the baseline year. The SCD group was followed for 3 years and divided into SCD-Stable and SCD-Decline groups based on scores of Mini-Mental State Examination. No significant differences in PAC of the baseline year were found between SCD-Stable and SCD-Decline groups. ConclusionsThe SCD group demonstrated reduced theta–gamma PAC in the precuneus. SignificanceSubjective perception of cognitive decline is reflected by objective alterations of brain function.

Unraveling Sex Differences in Affect Processing: Unique Oscillatory Signaling Dynamics in the Infralimbic Cortex and Nucleus Accumbens Shell

BackgroundNegative affect is prevalent in psychiatric diseases such as depression and addiction. Projections from the infralimbic cortex (IL) to the nucleus accumbens shell (NAcSh) are causally linked to learned negative affect as 20 Hz optogenetic stimulation of this circuit reduces conditioned taste aversion (CTA) in male but not female rats. However, the prior study did not provide insight into how innate versus learned negative affect are processed in these areas across sex. MethodsTo address this issue, local field potential activity was simultaneously recorded in the IL and NAcSh in response to intraoral infusion of rewarding (saccharin) and aversive (quinine) tastants and following induction of a CTA in male and female Sprague Dawley rats. ResultsLocal field potential oscillatory activity within each brain region to saccharin varied across sex. In males, CTA increased IL resting-state power, which was correlated with the strength of the learned aversion, and reduced beta power and IL-NAcSh coherence. In females, CTA increased gamma power in the NAcSh. Similar effects were observed in males and females after CTA in theta-low gamma phase-amplitude coupling. Finally, while quinine produced similar effects in oscillatory power across sex, females showed differences in phase-amplitude coupling within the NAcSh that may be linked to aversion resistance. ConclusionsWe revealed sex-specific hedonic processing in the IL and NAcSh and how oscillatory signaling is disrupted in learned negative affect, revealing translationally relevant insight into potential treatment strategies that can help to reduce the deleterious effects of learned negative affect in psychiatric illnesses.

Transcranial ultrasound stimulation modulates neural activities during NREM and REM depending on the stimulation phase of slow oscillations and theta waves in the hippocampus.

Modulation of the hippocampal neural activity by low-intensity transcranial ultrasound stimulation depends on the phase of theta rhythm and can also regulate sleep rhythm. However, until now, the modulatory effect of ultrasound stimulation on neural activity in different sleep states depending on the phase of local field potential stimulation in the hippocampus was unclear. To answer this question, closed-loop ultrasound stimulation was applied to in-phase (upstate)/out-of-phase slow oscillations in the hippocampus during non-rapid eye movement sleep, and to the peaks and troughs of theta oscillations in the hippocampus during wake in a mouse model. Local field potential of the hippocampus within 3-h after the ultrasound stimulation during light-on sleep cycle was recorded. We found that (i) under slow-oscillation in-phase stimulation, ultrasound stimulation upregulated the non-rapid eye movement ratio and decreased the wake ratio. Furthermore, it increased the ripple density during non-rapid eye movement and enhanced the coupling of the spindle-ripple during non-rapid eye movement as well as the theta-high gamma phase-amplitude coupling during the REM period. In addition, theta during the REM period showed a more stable oscillation mode. (ii) Under slow-oscillation out-of-phase stimulation, ultrasound stimulation increased the density of ripple during non-rapid eye movement and enhanced the theta-high gamma phase-amplitude coupling strength during REM. Furthermore, theta oscillations during REM were significantly slower and showed higher variability. (iii) Under the phase-locked peak and trough stimulation of theta oscillation, ultrasound stimulation increased the ripple density during non-rapid eye movement, weakened the coupling strength of spindle-ripple during non-rapid eye movement, and enhanced theta-high gamma phase-amplitude coupling during REM. However, theta oscillation mode was not changed significantly during REM. The above results suggest that the regulatory effect of ultrasound stimulation on neural activity in different sleep states depends on the stimulation phases of slow oscillations and theta waves in the hippocampus.

Disruption of hippocampal neuronal circuit function depends upon behavioral state in the APP/PS1 mouse model of Alzheimer’s disease

The Alzheimer’s disease-associated peptide amyloid-beta (Aβ) has been associated with neuronal hyperactivity under anesthesia, but clinical trials of anticonvulsants or neural system suppressors have, so far, failed to improve symptoms in AD. Using simultaneous hippocampal calcium imaging and electrophysiology in freely moving mice expressing human Aβ, here we show that Aβ aggregates perturbed neural systems in a state-dependent fashion, driving neuronal hyperactivity in exploratory behavior and slow wave sleep (SWS), yet suppressing activity in quiet wakefulness (QW) and REM sleep. In exploratory behavior and REM sleep, Aβ impaired hippocampal theta–gamma phase-amplitude coupling and altered neuronal synchronization with theta. In SWS, Aβ reduced cortical slow oscillation (SO) power, the coordination of hippocampal sharp wave-ripples with both the SO and thalamocortical spindles, and the coordination of calcium transients with the sharp wave-ripple. Physostigmine improved Aβ-associated hyperactivity in exploratory behavior and hypoactivity in QW and expanded the range of gamma that coupled with theta phase, but exacerbated hypoactivity in exploratory behavior. Together, these findings show that the effects of Aβ alone on hippocampal circuit function are profoundly state dependent and suggest a reformulation of therapeutic strategies aimed at Aβ induced hyperexcitability.

Neuromodulation in the developing visual cortex after long-term monocular deprivation.

Neural dynamics are altered in the primary visual cortex (V1) during critical period monocular deprivation (MD). Synchronization of neural oscillations is pertinent to physiological functioning of the brain. Previous studies have reported chronic disruption of V1 functional properties such as ocular dominance, spatial acuity, and binocular matching after long-term monocular deprivation (LTMD). However, the possible neuromodulation and neural synchrony has been less explored. Here, we investigated the difference between juvenile and adult experience-dependent plasticity in mice from intracellular calcium signals with fluorescent indicators. We also studied alterations in local field potentials power bands and phase-amplitude coupling (PAC) of specific brain oscillations. Our results showed that LTMD in juveniles causes higher neuromodulatory changes as seen by high-intensity fluorescent signals from the non-deprived eye (NDE). Meanwhile, adult mice showed a greater response from the deprived eye (DE). LTMD in juvenile mice triggered alterations in the power of delta, theta, and gamma oscillations, followed by enhancement of delta-gamma PAC in the NDE. However, LTMD in adult mice caused alterations in the power of delta oscillations and enhancement of delta-gamma PAC in the DE. These markers are intrinsic to cortical neuronal processing during LTMD and apply to a wide range of nested oscillatory markers.

Altered gamma oscillations and beta–gamma coupling in drug-naive first-episode major depressive disorder: Association with sleep and cognitive disturbance

ObjectiveGamma oscillations contribute to the pathogenesis mechanisms of major depressive disorder (MDD) have been proposed, but gamma activity is not well characterized. This study is the first attempt to investigate the altered gamma oscillations in first-episode MDD, particularly the beta–gamma coupling, and to determine the potential symptomatic relationship with the identified gamma dysregulation. MethodsResting electroencephalography was recorded for 43 drug-naive first-episode MDD and 57 healthy control (HC) subjects. Integrated analysis of relative spectral power, weighted phase lag index, and phase–amplitude coupling (PAC) were utilized to reveal the alterations of gamma activities. Pearson's correlation was implemented to identify the relationship between altered gamma activities and the clinical depressive symptoms, which were categorized into four factors: anxiety somatization, retardation, cognitive disturbance, and sleep disturbance. ResultsCompared with HC subjects, MDD patients showed not only significantly decreased gamma powers in the left temporal and the bilateral occipital regions but also weakened gamma connectivity between the left hemisphere and the right frontal region. Furthermore, attenuated beta–gamma PAC of MDD patients was observed in the left temporal regions. Importantly, the suppression of left occipital mid- and high gamma oscillations were negatively correlated with sleep disturbance, while the deficits in left temporal beta–mid-gamma PAC and beta–high gamma PAC showed negative correlations with cognitive disturbance. LimitationsImportant limitations are the small sample size and the possible inclusion of bipolar depression in the MDD group. ConclusionsOur findings provide the first evidence that in first-episode MDD, aberrant gamma powers and beta–gamma coupling are associated with sleep and cognitive impairments, respectively, deepening our understanding of the physiological mechanisms underlying sleep and cognitive symptoms in first-episode MDD. Altered gamma oscillations emerge as promising biomarkers for diagnosing MDD.

Neural dynamics differentially encode phrases and sentences during spoken language comprehension

Human language stands out in the natural world as a biological signal that uses a structured system to combine the meanings of small linguistic units (e.g., words) into larger constituents (e.g., phrases and sentences). However, the physical dynamics of speech (or sign) do not stand in a one-to-one relationship with the meanings listeners perceive. Instead, listeners infer meaning based on their knowledge of the language. The neural readouts of the perceptual and cognitive processes underlying these inferences are still poorly understood. In the present study, we used scalp electroencephalography (EEG) to compare the neural response to phrases (e.g., the red vase) and sentences (e.g., the vase is red), which were close in semantic meaning and had been synthesized to be physically indistinguishable. Differences in structure were well captured in the reorganization of neural phase responses in delta (approximately <2 Hz) and theta bands (approximately 2 to 7 Hz),and in power and power connectivity changes in the alpha band (approximately 7.5 to 13.5 Hz). Consistent with predictions from a computational model, sentences showed more power, more power connectivity, and more phase synchronization than phrases did. Theta-gamma phase-amplitude coupling occurred, but did not differ between the syntactic structures. Spectral-temporal response function (STRF) modeling revealed different encoding states for phrases and sentences, over and above the acoustically driven neural response. Our findings provide a comprehensive description of how the brain encodes and separates linguistic structures in the dynamics of neural responses. They imply that phase synchronization and strength of connectivity are readouts for the constituent structure of language. The results provide a novel basis for future neurophysiological research on linguistic structure representation in the brain, and, together with our simulations, support time-based binding as a mechanism of structure encoding in neural dynamics.

Prefrontal theta phase-dependent rTMS-induced plasticity of cortical and behavioral responses in human cortex

BackgroundPrefrontal theta oscillations are involved in neuronal information transfer and retention. Phases along the theta cycle represent varied excitability states, whereby high-excitability states correspond to high-frequency neuronal activity and heightened capacity for plasticity induction, as demonstrated in animal studies. Human studies corroborate this model and suggest a core role of prefrontal theta activity in working memory (WM).Objective/Hypothesis: We aimed at modulating prefrontal neuronal excitability and WM performance in healthy humans, using real-time EEG analysis for triggering repetitive transcranial magnetic stimulation (rTMS) theta-phase synchronized to the left dorsomedial prefrontal cortex. Methods16 subjects underwent 3 different rTMS interventions on separate days, with pulses triggered according to the individual's real-time EEG activity: 400 rTMS gamma-frequency (100 Hz) triplet bursts applied during either the negative peak of the prefrontal theta oscillation, the positive peak, or at random phase. Changes in cortical excitability were assessed with EEG responses following single-pulse TMS, and behavioral effects by using a WM task. ResultsNegative-peak rTMS increased single-pulse TMS-induced prefrontal theta power and theta-gamma phase-amplitude coupling, and decreased WM response time. In contrast, positive-peak rTMS decreased prefrontal theta power, while no changes were observed after random-phase rTMS. ConclusionFindings point to the feasibility of EEG-TMS technology in a theta–gamma phase–amplitude coupling mode for effectively modifying WM networks in human prefrontal cortex, with potential for therapeutic applications.

Theta low-gamma phase amplitude coupling in the human orbitofrontal cortex increases during a conflict-processing task

Objective. The human orbitofrontal cortex (OFC) is involved in automatic response inhibition and conflict processing, but the mechanism of frequency-specific power changes that control these functions is unknown. Theta and gamma activity have been independently observed in the OFC during conflict processing, while theta–gamma interactions in other brain areas have been noted primarily in studies of memory. Within the OFC, it is possible that theta–gamma phase amplitude coupling (PAC) drives conflict processing. This study aims to characterize the coupled relationship between theta and gamma frequency bands in the OFC during conflict processing using a modified Stroop task. Approach. Eight epilepsy patients implanted with OFC stereotactic electroencephalography electrodes participated in a color-word modified Stroop task. PAC between theta phase and gamma amplitude was assessed to determine the timing and magnitude of neural oscillatory changes. Group analysis was conducted using a non-parametric cluster-permutation t-test on coherence values. Main results. Theta-low gamma (LG) PAC significantly increased in five out of eight patients during successful trials of the incongruent condition compared with the congruent condition. Significant increases in theta-LG PAC were most prominent during cue processing 200–800 ms after cue presentation. On group analysis, trial-averaged mean theta-LG PAC was statistically significantly greater in the incongruent condition compared to the congruent condition (p < 0.001, Cohen’s d = 0.51). Significance. For the first time, we report that OFC theta phase and LG amplitude coupling increases during conflict resolution. Given the delayed onset after cue presentation, OFC theta-LG PAC may contribute to conflict processing after conflict detection and before motor response. This explanation follows the hypothesis that global theta waves modulate local gamma signals. Understanding this relationship within the OFC will help further elucidate the neural mechanisms of human conflict resolution.

Cortical oscillatory dysrhythmias in visual snow syndrome: a magnetoencephalography study.

Visual snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions such as tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously, we hypothesized that visual snow syndrome may be characterized by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8–13 Hz) power and increases in gamma-band power (40–70 Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localized to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p > 0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p = 0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings, suggesting that in visual snow syndrome, the visual cortex is hyperexcitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha–gamma phase–amplitude coupling, p < 0.05, indicating a potential excitation–inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down ‘noise-cancellation’ mechanisms. Overall, these results suggest that rhythmical brain activity in the primary visual cortex is both hyperexcitable and disorganized in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia.

Decreased Phase-Amplitude Coupling Between the mPFC and BLA During Exploratory Behaviour in Chronic Unpredictable Mild Stress-Induced Depression Model of Rats.

Depression is a common neuropsychiatric illness observed worldwide, and reduced interest in exploration is one of its symptoms. The control of dysregulated medial prefrontal cortex (mPFC) over the basolateral amygdala (BLA) is related to depression. However, the oscillation interaction in the mPFC-BLA circuit has remained elusive. Therefore, this study used phase–amplitude coupling (PAC), which provides complicated forms of information transmission by the phase of low-frequency rhythm, modulating the amplitude of high-frequency rhythm, and has a potential application for the treatment of neurological disease. The chronic unpredictable mild stress (CUMS) was used to prepare the rat models of depression. Moreover, multichannel in vivo recording was applied to obtain the local field potentials (LFPs) of the mPFC, the BLA in rats in control, and CUMS groups, while they explored the open field. The results showed prominent coupling between the phase of theta oscillation (4–12 Hz) in the mPFC and the amplitude of high-gamma oscillation (70–120 Hz) in the BLA. Compared to the control group, this theta–gamma PAC was significantly decreased in the CUMS group, which was accompanied by the diminished exploratory behaviour. The results indicate that the coupling between the phase of theta in the mPFC and the amplitude of gamma in the BLA is involved in exploratory behaviour, and this decreased coupling may inhibit exploratory behaviour of rats exposed to CUMS.

Epileptogenic Zone Location of Temporal Lobe Epilepsy by Cross-Frequency Coupling Analysis.

Epilepsy is a chronic brain disease with dysfunctional brain networks, and electroencephalography (EEG) is an important tool for epileptogenic zone (EZ) identification, with rich information about frequencies. Different frequency oscillations have different contributions to brain function, and cross-frequency coupling (CFC) has been found to exist within brain regions. Cross-channel and inter-channel analysis should be both focused because they help to analyze how epilepsy networks change and also localize the EZ. In this paper, we analyzed long-term stereo-electroencephalography (SEEG) data from 17 patients with temporal lobe epilepsy. Single-channel and cross-channel CFC features were combined to establish functional brain networks, and the network characteristics under different periods and the localization of EZ were analyzed. It was observed that theta–gamma phase amplitude coupling (PAC) within the electrodes in the seizure region increased during the ictal (p < 0.05). Theta–gamma and delta–gamma PAC of cross-channel were enhanced in the early and mid-late ictal, respectively. It was also found that there was a strong cross-frequency coupling state between channels of EZ in the functional network during the ictal, along with a more regular network than interictal. The accuracy rate of EZ localization was 82.4%. Overall, the combination of single-channel and multi-channel cross-band coupling analysis can help identify seizures and localize EZ for temporal lobe epilepsy. Rhythmic coupling reveals a relationship between the functional network and the seizure status of epilepsy.