Strength Of Phase-amplitude Coupling Research Articles

Transcranial Ultrasound Stimulation Improves Memory Performance of Parkinsonian Mice.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism. Ultrasonography was used for 7-day stimulation of the CA1 in transgenic mice with PD. The working memory ability of the PD mice was then tested using novel object discrimination, and the local field potential and spikes in the mice CA1 were recorded at the same time as in the behavioral test. We found that ultrasound stimulation of the PD mice CA1 for 4 days: 1) significantly increased their learning and memory ability, although the learning and memory ability on the 7th day after the stimulation stopped was not significantly different from that before stimulation (P>0.05); 2) significantly increased the relative power of theta, low gamma, and high gamma frequency bands of the local field potential, and the phase amplitude coupling strength between theta and low gamma and between theta and high gamma; and 3) modulated the phase-locking angle between the spike of interneuron and theta wave to a 180°-360° rise cycle. Transcranial ultrasound stimulation can improve the learning and memory abilities of PD mice, and evoking neural oscillations in the CA1 is the potential mechanism.

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.

Effect of low-intensity transcranial ultrasound stimulation on theta and gamma oscillations in the mouse hippocampal CA1.

Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation (TUS) can eliminate hippocampal neural activity. However, until now, it has remained unclear how ultrasound modulates theta and gamma oscillations in the hippocampus under different behavioral states. In this study, we used ultrasound to stimulate the CA1 in mice in anesthesia, awake and running states, and we simultaneously recorded the local field potential of the stimulation location. We analyzed the power spectrum, phase-amplitude coupling (PAC) of theta and gamma oscillations, and their relationship with ultrasound intensity. The results showed that (i) TUS significantly enhanced the absolute power of theta and gamma oscillations under anesthesia and in the awake state. (ii) The PAC strength between theta and gamma oscillations is significantly enhanced under the anesthesia and awake states but is weakened under the running state with TUS. (iii) Under anesthesia, the relative power of theta decreases and that of gamma increases as ultrasound intensity increases, and the result under the awake state is opposite that under the anesthesia state. (iv) The PAC index between theta and gamma increases as ultrasound intensity increases under the anesthesia and awake states. The above results demonstrate that TUS can modulate theta and gamma oscillations in the CA1 and that the modulation effect depends on behavioral states. Our study provides guidance for the application of ultrasound in modulating hippocampal function.

Phase-amplitude coupling between low- and high-frequency activities as preoperative biomarker of focal cortical dysplasia subtypes

ObjectiveTo evaluate whether ictal phase-amplitude coupling (PAC) between high-frequency activity and low-frequency activity could be used as a preoperative biomarker of Focal Cortical Dysplasia (FCD) subtypes. We hypothesize that FCD seizures present unique PAC characteristics that may be linked to their specific histopathological features. MethodsWe retrospectively examined 12 children with FCD and refractory epilepsy who underwent successful epilepsy surgery. We identified ictal onsets recorded with stereo-EEG. We estimated the strength of PAC between low-frequencies and high-frequencies for each seizure by means of modulation index. Generalized mixed effect models and receiver operating characteristic (ROC) curve analysis were used to test the association between ictal PAC and FCD subtypes. ResultsIctal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ-electrodes (p < 0.005). No differences in ictal PAC were found on non-SOZ electrodes. Pre-ictal PAC registered on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9 (p < 0.05). ConclusionsThe correlations between histopathology and neurophysiology provide evidence for the contribution of ictal PAC as a preoperative biomarker of FCD subtypes. SignificanceDeveloped into a proper clinical application, such a technique may help improve clinical management and facilitate the prediction of surgical outcome in patients with FCD undergoing stereo-EEG monitoring.

Electroencephalographic delta and alpha oscillations reveal phase-amplitude coupling in paediatric patients undergoing sevoflurane-based general anaesthesia

BackgroundSevoflurane-induced anaesthesia generates frontal alpha oscillations as early as 6 months of age, whereas strong delta oscillations are present at birth. In adults, delta oscillations and alpha oscillations are coupled: the phase of delta waves modulates the amplitude of alpha oscillations in a phenomenon known as phase-amplitude coupling. We hypothesise that delta-alpha phase-amplitude coupling exists in young children and is a feature of sevoflurane-based general anaesthesia distinct from emergence after anaesthesia. MethodsElectroencephalographic data from 31 paediatric patients aged 10 months to 3 yr undergoing elective surgery with sevoflurane-based anaesthesia were analysed retrospectively. Delta-alpha phase-amplitude coupling was evaluated during maintenance of anaesthesia and during emergence. ResultsDelta-alpha phase-amplitude coupling was observed in the study population. Strength of phase-amplitude coupling, represented by the delta-alpha mean amplitude vector, was greater during general anaesthesia than during emergence (Wilcoxon paired signed-rank test, Z=3.107, P=0.002). Frontal alpha amplitude during anaesthesia was not uniformly distributed across all delta phases. During general anaesthesia, alpha power was restricted to the positive phase of the delta wave (omnibus circular uniformity, general anaesthesia: P<0.001, mean phase: 114º; 99% confidence interval: 90º–139º; emergence: P=0.35, mean phase 181º, 99% confidence interval: 110º–253º). ConclusionsSevoflurane-based anaesthesia is associated with delta-alpha phase-amplitude coupling in paediatric patients. These findings improve our understanding of cortical dynamics in children undergoing general anaesthesia, which might improve paediatric intraoperative depth of anaesthesia monitoring techniques.

A hippocampal-entorhinal cortex neuronal network for dynamical mechanisms of epileptic seizure.

Temporal lobe epilepsy (TLE) is thought to be associated with neuronal hyperexcitability in the hippocampal-entorhinal cortical (EC) circuit. Due to the complexity of the hippocampal-EC network connections, the biophysical mechanisms of the different circuits in epilepsy generation and propagation are still not fully established. In this work, we propose a hippocampal-EC neuronal network model to explore the mechanism of epileptic generation. We demonstrate that enhanced excitability of pyramidal neurons in cornu ammonis 3 (CA3) can drive hippocampal-EC to produce a transition from background to seizure state and cause exaggerated phase-amplitude coupling (PAC) phenomenon of theta modulated high-frequency oscillations (HFO) in CA3, cornu ammonis 1 (CA1), dentate gyrus, and EC. Interestingly, PAC strength indirectly responds to the degree of CA3 pyramidal (PY) neuron hyperexcitability, suggesting that PAC can be used as a potential marker of seizures. Furthermore, we find that enhanced synaptic connectivity of mossy cells to granule cells and CA3 PY neurons drives the system to produce epileptic discharges. These two channels may play a key role in mossy fiber sprouting. In particular, the PAC phenomenon of delta-modulated HFO and theta-modulated HFO can be generated according to the different degrees of moss fiber sprouting. Finally, the results suggest that hyperexcitability of stellate cells in EC can lead to seizures, which supports the argument that EC can act as an independent source of seizures. Overall, these results highlight the key role of different circuits in seizures, providing a theoretical basis and new insights into the generation and propagation of TLE.

Simultaneous Gut-Brain Electrophysiology Shows Cognition and Satiety Specific Coupling

Recent studies, using high resolution magnetoencephalography (MEG) and electrogastrography (EGG), have shown that during resting state, rhythmic gastric physiological signals are linked with cortical brain oscillations. Yet, gut-brain coupling has not been investigated with electroencephalography (EEG) during cognitive brain engagement or during hunger-related gut engagement. In this study in 14 young adults (7 females, mean ± SD age 25.71 ± 8.32 years), we study gut-brain coupling using simultaneous EEG and EGG during hunger and satiety states measured in separate visits, and compare responses both while resting as well as during a cognitively demanding working memory task. We find that EGG-EEG phase-amplitude coupling (PAC) differs based on both satiety state and cognitive effort, with greater PAC modulation observed in the resting state relative to working memory. We find a significant interaction between gut satiation levels and cognitive states in the left fronto-central brain region, with larger cognitive demand based differences in the hunger state. Furthermore, strength of PAC correlated with behavioral performance during the working memory task. Altogether, these results highlight the role of gut-brain interactions in cognition and demonstrate the feasibility of these recordings using scalable sensors.

Comparison of event-related modulation index and traditional methods for evaluating phase-amplitude coupling using simulated brain signals.

The investigation of brain oscillations and connectivity has become an important topic in the recent decade. There are several types of interactions between neuronal oscillations, and one of the most interesting among these interactions is phase-amplitude coupling (PAC). Several methods have been proposed to measure the strength of PAC, including the phase-locking value, circular-linear correlation, and modulation index. In the current study, we compared these traditional PAC methods with simulated electroencephalogram signals. Further, to assess the PAC value at each time point, we also compared two recently established methods, event-related phase-locking value and event-related circular-linear correlation, with our newly proposed event-related modulation index (ERMI). Results indicated that the ERMI has better temporal resolution and is more tolerant to noise than the other two event-related methods, suggesting the advantages of utilizing ERMI in evaluating the strength of PAC within a brain region.

Phase-locked closed-loop ultrasound stimulation modulates theta and gamma rhythms in the mouse hippocampus.

Previous studies have demonstrated that open-loop transcranial ultrasound stimulation (TUS) can modulate theta and gamma rhythms of the local field potentials (LFPs) in the mouse hippocampus; however, the manner in which closed-loop TUS with different pressures based on phase-locking of theta rhythms modulates theta and gamma rhythm remains unclear. In this study, we established a closed-loop TUS system, which can perform closed-loop TUS by predicting the peaks and troughs of the theta rhythm. Comparison of the power, sample entropy and complexity, and phase-amplitude coupling (PAC) between the theta and gamma rhythms under peak and trough stimulation of the theta rhythm revealed the following: (1) the variation in the absolute power of the gamma rhythm and the relative power of the theta rhythm under TUS at 0.6–0.8 MPa differ between peak and trough stimulation; (2) the relationship of the sample entropy of the theta and gamma rhythms with ultrasound pressure depends on peak and trough stimulation; and (3) peak and trough stimulation affect the PAC strength between the theta and gamma rhythm as a function of ultrasound pressure. These results demonstrate that the modulation of the theta and gamma rhythms by ultrasound pressure depends on peak and trough stimulation of the theta rhythm in the mouse hippocampus.

The dysfunction of mGluRIIs is involved in the disorder of hippocampal neural network in diabetic mice model.

Cognitive dysfunction is a high incidence of diabetes mellitus (DM). However, the relationship between DM-induced cognitive defect and neuronal network oscillations is still unknown. In this study, adult male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) to duplicate DM. After 12weeks, local field potentials were recorded in the perforant fiber pathway (PP) and dentate gyrus (DG) regions. Data showed that mice in the STZ group exhibited impairment of spatial learning and memory by the Morris Water Mazetest. The low gamma (LG) and high gamma (HG) power were increased in the PP and DG areas of the STZ group. Moreover, the phase synchronization and the information flow at theta and LG rhythms between the PP and DG areas were decreased, and the theta-LG phase-amplitude coupling strength was markedly reduced in the PPregion, DG region, and the PP-DG pathway in the STZ group. Additionally, the concentration of glutamate was increased by thehigh-performance liquid chromatography. Moreover, the NR2B and PSD95 expressions were markedly reduced, and the Akt/GSK-3β pathway was inhibited. Interestingly, the expressions of mGluRIIs (mGluR2 and mGluR3) were significantly decreased. The reduction of mGluRIIs may limit their function, such as restricting presynaptic glutamate release and reversing the dysfunction of NR2B via Akt/GSK-3β signaling pathway. In conclusion, our data suggest that DM alters the hippocampal neural network partly related to the dysfunction of mGluRIIs.

Assessing differential representation of hand movements in multiple domains using stereo-electroencephalographic recordings

Invasive brain-computer interfaces (BCI) have made great progress in the reconstruction of fine hand movement parameters for paralyzed patients, where superficial measurement modalities including electrocorticography (ECoG) and micro-array recordings are mostly used. However, these recording techniques typically focus on the signals from the sensorimotor cortex, leaving subcortical regions and other cortical regions related to the movements largely unexplored. As an intracranial recording technique for the presurgical assessments of brain surgery, stereo-encephalography (SEEG) inserts depth electrodes containing multiple contacts into the brain and thus provides the unique opportunity for investigating movement-related neural representation throughout the brain. Although SEEG samples neural signals with high spatial-temporal resolutions, its potential of being used to build BCIs has just been realized recently, and the decoding of SEEG activity related to hand movements has not been comprehensively investigated yet. Here, we systematically evaluated the factors influencing the performance of movement decoding using SEEG signals recorded from 32 human subjects performing a visually-cued hand movement task. Our results suggest that multiple regions in both lateral and depth directions present significant neural selectivity to the task, whereas the sensorimotor area, including both precentral and postcentral cortex, carries the richest discriminative neural information for the decoding. The posterior parietal and prefrontal cortex contribute gradually less, but still rich sources for extracting movement parameters. The insula, temporal and occipital cortex also contains useful task-related information for decoding. Under the cortex layer, white matter presents decodable neural patterns but yields a lower accuracy (42.0 ± 0.8%) than the cortex on average (44.2 ± 0.8%, p<0.01). Notably, collectively using neural signals from multiple task-related areas can significantly enhance the movement decoding performance by 6.9% (p<0.01) on average compared to using a single region. Among the different spectral components of SEEG activity, the high gamma and delta bands offer the most informative features for hand movements reconstruction. Additionally, the phase-amplitude coupling strength between these two frequency ranges correlates positively with the performance of movement decoding. In the temporal domain, maximum decoding accuracy is first reached around 2 s after the onset of movement commands. In sum, this study provides valuable insights for the future motor BCIs design employing both SEEG recordings and other recording modalities.

Delineation of the epileptogenic zone by Phase-amplitude coupling in patients with Bottom of Sulcus Dysplasia

PurposeThe removal of the bottom of sulcus dysplasia (BOSD) often includes the gyral crown; however, this method has been controversial. We hypothesized that the epileptogenic zone of the BOSD does not include the gyral crown. To reveal the depth and extent of the epileptogenic zone of the BOSD, we applied the two electrophysiological modalities: (1) the occurrence rate (OR) of high-frequency oscillations (HFOs) and (2) modulation index (MI), reflecting the strength of phase-amplitude coupling between HFOs and slow oscillations. MethodsWe investigated the ripples [80–200 Hz] and fast ripples [200–300 Hz]) in HFOs and MI (HFOs [80–300 Hz] and slow oscillations [3–4 Hz]). We opened the sulcus at the BOSD and implanted the subdural electrodes directly over the MRI visible lesion. All patients (n = 3) underwent lesionectomy and the gyral crown was preserved. ResultsPathological findings demonstrated focal cortical dysplasia type IIb and seizure freedom was achieved. The OR of the HFOs was not significantly different between the BOSD and the gyral crown. In contrast, the MI between HFOs and slow oscillations in the BOSD was significantly higher than that in the gyral crown. ConclusionHigh MI values distinguished the epileptogenic BOSD from the non-epileptogenic gyral crowns. MI could be a more informative biomarker of epileptogenicity than the OR of HFOs in a subset of patients with the BOSD.

Abnormal brain activity in fronto-central regions in mental disorders with suicide: An EEG Study.

Suicide is a global health problem, and early and accurate identification of suicide attempt individuals has very important clinical significance. Thus the exploration of neurobiological mechanisms underlying suicidal behavior is crucial for systematically preventing suicide. However, the neurophysiological biomarkers for identifying affective disorders with suicidal attempt are remain unknown. Here, we recruited 28 patients with mental disorders from Tianjin Anding Hospital, and the subjects were divided into suicide attempt group (SA=14) and non suicide attempt group (NSA=14) according to whether they had attempted suicide. We also recruited 14 healthy subjects matched with age and sex ratio as healthy control group (HC=14). By recording the electroencephalogram(EEG) data of 60 electrodes in resting state for eight minutes (four minutes with open eyes and four minutes with close eyes), the absolute power of five frequency bands( delta(0.5-4Hz), theta(4-8Hz), alpha(8-13Hz), beta (13-30Hz), gamma(30-65Hz)) were analyzed to explore the changes of brain rhythm. And then the Modulation index (MI) was calculated to quantify the intensity of phase amplitude coupling (PAC) between different frequency bands in different brain regions, so as to observe the mechanism of neuronal synchronization in different frequency bands. We found that the absolute power of SA group was significantly higher than NSA group and HC group in delta (P<0.05), beta (P<0.05) and gamma (P<0.05) bands. The PAC strength between beta and gamma was calculated and it showed that the PAC strength of SA group was significantly weaker than NSA group in fronto-central regions, indicating that decreased synchronization between neurons could bring about brain function impairment. These findings suggest that the brain electrical activity in the fronto-central regions of the SA group may be damaged, which may lead to an increased suicidal risk in mental disoders. The EEG activity in delta, beta, gamma band and PAC in fronto-central regions may be used as a potential clinical biomarker for preventing suicide.

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.

EEG Phase-Amplitude Coupling Strength and Phase Preference: Association with Age over the First Three Years after Birth.

Phase-amplitude coupling (PAC), the coupling of the phase of slower electrophysiological oscillations with the amplitude of faster oscillations, is thought to facilitate dynamic integration of neural activity in the brain. Although the brain undergoes dramatic change and development during the first few years of life, how PAC changes through this developmental period has not been extensively studied. Here, we examined PAC through electroencephalography (EEG) data collected during an awake, eyes-open EEG collection paradigm in 98 children between the ages of three months and three years. We employed non-parametric clustering methods to identify areas of significant PAC across a range of frequency pairs and electrode locations, and examined how PAC strength and phase preference develops in these areas. We found that PAC, primarily between the α-β and γ frequencies, was positively correlated with age from early infancy to early childhood (p = 2.035 × 10−6). Additionally, we found γ over anterior electrodes coupled with the rising phase of the α-β waveform, while γ over posterior electrodes coupled with the falling phase of the α-β waveform; this regionalized phase preference became more prominent with age. This opposing trend may reflect each region’s specialization toward feedback or feedforward processing, respectively, suggesting opportunities for back translation in future studies.

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome

BackgroundPhelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS.MethodsHere, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity.ResultsWe find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011).ConclusionsIncreased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials.

Disc1 gene down-regulation impaired synaptic plasticity and recognition memory via disrupting neural activity in mice

The gene of Disrupted-in-schizophrenia 1 (Disc1) is closely related to mental diseases with cognitive deficits, but there are few studies on the changes in neural oscillations and recognition memory. Neural oscillations plays a key role in the nervous system in a dynamic form, which is closely related to advanced cognitive activities such as information processing and memory consolidation. Hence, we aimed to investigate if Disc1 knockdown disrupted the normal pattern of neural activities in the mouse hippocampus network, and determined if quantitative neural oscillation approach could be a potential diagnostic tool for mental disorders. In the study, we reported that Disc1 gene, downregulated by short-hairpin RNA (shRNA), not only induced anxiety-like behavior and sociability impairment but also damaged both synaptic plasticity and recognition memory in mice. Moreover, Disc1 knockdown mice exhibited evidently abnormal power spectral distributions, reduced phase synchronizations, and decreased phase-amplitude coupling strength compared to that of normal animals. In addition, transcriptome analyses showed that there were clearly transcriptional changes in Disc1 knockdown mice. Altogether, our findings suggest that the abnormal pattern of neural activities in the hippocampus network disrupts information processing and finally leads to the impairments of synaptic plasticity and recognition in Disc1 knockdown mice, which are possibly associated with the obstruction of neurotransmitter transmission. Importantly, the data imply that the analysis of neural oscillation pattern provides a potential diagnosis approach for mental disorders.

Objective interictal electrophysiology biomarkers optimize prediction of epilepsy surgery outcome.

Researchers have looked for rapidly- and objectively-measurable electrophysiology biomarkers that accurately localize the epileptogenic zone. Promising candidates include interictal high-frequency oscillation and phase-amplitude coupling. Investigators have independently created the toolboxes that compute the high-frequency oscillation rate and the severity of phase-amplitude coupling. This study of 135 patients determined what toolboxes and analytic approaches would optimally classify patients achieving post-operative seizure control. Four different detector toolboxes computed the rate of high-frequency oscillation at ≥80 Hz at intracranial EEG channels. Another toolbox calculated the modulation index reflecting the strength of phase-amplitude coupling between high-frequency oscillation and slow-wave at 3–4 Hz. We defined the completeness of resection of interictally-abnormal regions as the subtraction of high-frequency oscillation rate (or modulation index) averaged across all preserved sites from that averaged across all resected sites. We computed the outcome classification accuracy of the logistic regression-based standard model considering clinical, ictal intracranial EEG and neuroimaging variables alone. We then determined how well the incorporation of high-frequency oscillation/modulation index would improve the standard model mentioned above. To assess the anatomical variability across non-epileptic sites, we generated the normative atlas of detector-specific high-frequency oscillation and modulation index. Each atlas allowed us to compute the statistical deviation of high-frequency oscillation/modulation index from the non-epileptic mean. We determined whether the model accuracy would be improved by incorporating absolute or normalized high-frequency oscillation/modulation index as a biomarker assessing interictally-abnormal regions. We finally determined whether the model accuracy would be improved by selectively incorporating high-frequency oscillation verified to have high-frequency oscillatory components unattributable to a high-pass filtering effect. Ninety-five patients achieved successful seizure control, defined as International League against Epilepsy class 1 outcome. Multivariate logistic regression analysis demonstrated that complete resection of interictally-abnormal regions additively increased the chance of success. The model accuracy was further improved by incorporating z-score normalized high-frequency oscillation/modulation index or selective incorporation of verified high-frequency oscillation. The standard model had a classification accuracy of 0.75. Incorporation of normalized high-frequency oscillation/modulation index or verified high-frequency oscillation improved the classification accuracy up to 0.82. These outcome prediction models survived the cross-validation process and demonstrated an agreement between the model-based likelihood of success and the observed success on an individual basis. Interictal high-frequency oscillation and modulation index had a comparably additive utility in epilepsy presurgical evaluation. Our empirical data support the theoretical notion that the prediction of post-operative seizure outcomes can be optimized with the consideration of both interictal and ictal abnormalities.

Epileptogenic modulation index and synchronization in hypsarrhythmia of West syndrome secondary to perinatal arterial ischemic stroke

ObjectivePerinatal arterial ischemic stroke (PAIS) is associated with epileptic spasms of West syndrome (WS) and long term Focal epilepsy (FE). The mechanism of epileptogenic network generation causing hypsarrhythmia of WS is unknown. We hypothesized that Modulation index (MI) [strength of phase-amplitude coupling] and Synchronization likelihood (SL) [degree of connectivity] could interrogate the epileptogenic network in hypsarrhythmia of WS secondary to PAIS. MethodsWe analyzed interictal scalp electroencephalography (EEG) in 10 WS and 11 FE patients with unilateral PAIS. MI between gamma (30–70 Hz) and slow waves (3–4 Hz) was calculated to measure phase-amplitude coupling. SL between electrode pairs was analyzed in 9-frequency bands (5-delta, theta, alpha, beta, gamma) to examine inter- and intra-hemispheric connectivity. ResultsMI was higher in affected hemispheres in WS (p = 0.006); no differences observed in FE. Inter-hemispheric SL of 3-delta, theta, alpha, beta, gamma bands was significantly higher in WS (p < 0.001). In WS, modified Z-Score of intra-hemispheric SL values in 3-delta, theta, alpha, beta and gamma in the affected hemispheres were significantly higher than those in the unaffected hemispheres (p < 0.001) as well as 0.5–4 Hz (p = 0.004). ConclusionsThe significantly higher modulation in affected hemisphere and stronger inter- and intra-hemispheric connectivity generate hypsarrhythmia of WS secondary to PAIS. SignificanceEpileptogenic cortical-subcortical transcallosal networks from affected hemisphere post-PAIS provokes infantile spasms.