Neuroscience Letters

Microtubules (MTs) are essential cytoskeletal structures in neurons that generate electrical oscillations in the frequency range of mammalian brain waves. However, the role of these MT oscillations in brain function remains largely unknown. Here, we sought to gain insight into MT electrical oscillatory activity from different brain regions with specific functions, the hippocampus and the neocortex from the adult rat brain. We obtained local field potentials (LFP) from the frozen brain regions under non-depolarized (high external NaCl) and depolarized (high external KCl) saline solutions, observing spontaneous oscillations under both conditions. The electrical oscillations of the brain tissue had different amplitudes in the absence (0 mV) or presence (100 mV) of holding potential and were inhibited by the MT stabilizer paclitaxel. A frequency domain spectral analysis of the time records revealed the presence of two major peaks at approximately [~]38 Hz and [~]93 Hz in both preparations. However, the energy contribution of each peak was different in the hippocampus compared to neocortex. Coupled with our electron microscopy observations, these data suggest that rat brain MTs produce electrical oscillations with specific properties in the various regions of the mammalian brain, which could be partially related as their intra-axonal distributions. MT oscillations may be implicated in the wave coherence of brain activity, supporting their contribution to the concept of a brain central oscillator that drives its function.

Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p[&le;]0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p[&le;]0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.

BackgroundThe cellular prion protein (PrPC) has been associated with numerous cellular processes, such as cell differentiation and neurotransmission. Moreover, it was recently demonstrated that some functions were misattributed to PrPC since results were obtained from mouse models with genetic artifacts. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, like learning and memory, using the new strictly co-isogenic Prnp0/0 mouse (PrnpZH3/ZH3). Behavioral and operant conditioning tests were performed to evaluate memory and learning capabilities. In vivo electrophysiological recordings were carried out at CA3-CA1 synapses in living behaving mice, and spontaneous neuronal firing and network formation were monitored in primary neuronal cultures of PrnpZH3/ZH3 vs. wild-type mice. ResultsResults showed decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures. ConclusionIn conclusion, PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion might evoke a susceptible epileptogenic brain that would fail to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.

Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairment, but its neural mechanisms are not well known. Excitation (E) / inhibition (I) imbalance is considered as a key neurobiological mechanism of ASD, and several electroencephalography (EEG)-based E/I balance metrics have been proposed in the previous studies. The goal of the present research was to focus on these metrics abstracted from the speech perception task to investigate their relation to language/communication in autistic youths. We used a high-density 128-channel EEG to register neural responses during speech perception task in the sex- and age-matched groups of youths with ASD (N = 162) and typically developing (TD) controls (N = 144), aged 7-18 years old. The results revealed alterations in the E/I measures in the ASD group, pointing to a higher level of excitation or neural noise in the cortex as well as broadband reduction of spectral power during speech perception. A greater neural noise reflected in the reduction of aperiodic exponent and offset was associated with lower verbal communication skills in youths with ASD. The findings suggested that the higher noisiness in the cortical systems may be a relevant marker to monitor in relation to language/communication in ASD.

An axiomatic view in contemporary neuroscience is that EEG components such as event-related brain potentials (ERPs) and oscillations are directly interpretable as manifestations of biological processes that support sensory, motor, and cognitive constructs of interest. This premise justifies and propels research programs in laboratories worldwide, but with a substantial social and economic cost, warranted by the potential for basic-science discovery and the resulting bench-to-bedside transfer for health and disease. But a different premise would be more fruitful. This article proposes that EEG components in psychophysiological experiments relate to cognition indirectly through their more direct relationship with oculomotor action. The common experimental design that includes a baseline ocular fixation period preceding stimulus presentation provides an excellent template with which to develop the present proposal. Electrophysiological and eye-tracking evidence (3 published and 3 new data sets: 6 experiments, Ntotal = 204, in the context of face and affective picture viewing, reading, listening, rest, and microsleep) demonstrates how and why common conclusions, and reliance on them in clinical practice/treatment efficacy and drug development studies, are at best premature. Results indicate that the oculomotor system plays a mediating role between such EEG phenomena and cognition. Present evidence supports a complementary view of how EEG can shape the development of a broader thought horizon in psychophysiological theory and practice.

Early-life stress is known to impair neurodevelopment. Prior work from our group showed that prolonged physical and emotional separation necessitated by the medical needs of preterm infants (born <37 weeks) is associated with lower electroencephalogram (EEG) power in frontal areas, and that trend can be reversed by an intervention that enhances the physical and emotional contact between preterm infant and mother. Here we sought to model the changes in preterm infant frontal EEG power in a rodent model. We examined effects of daily maternal separation (MS) on frontal cortex electrophysiological (electrocorticography [EcoG]) activity in neonatal rats. We also explored the effects of dam-pup behavioral interactions on EcoG activity. From postnatal days (P) 2-10, rat pups were separated daily from their dam and isolated from their littermates for 3 hours. Control rats were normally reared. On P10, pups were implanted with telemetry devices and an electrode placed on the left frontal dura. EcoG activity was recorded during daily sessions over the next four days while pups remained in the home cage, as well as in response to a pup-dam isolation-reunion paradigm at P12. EcoG power was computed in 1 Hz frequency bins between 1-100 Hz. Dam and pup behavioral interactions during recording sessions were coded and synchronized to EcoG data. MS pups showed lower EcoG power during dam-pup interactions. These data parallel human and provide evidence of lower fronto-cortical activity as an early marker of early-life stress and possible mechanism for long-term effects of maternal separation on neurobehavioral development.

Epilepsy, the condition of recurrent unprovoked seizures resulting from a wide variety of causes, is one of the worlds most prominent brain syndrome. Seizures which are an expression of neuronal network dysfunction occur in a positive feedback loop of concomitant factors where seizures generate more seizures, including also neuro-inflammatory responses. Among other pathways involved in inflammatory responses, the JAK/STAT signaling pathway has been proposed to prevent epilepsy. In this work we tested on a model of temporal lobe epilepsy in-vitro, the hypothesis that acute inhibition of STAT3-phosphorylation - during epileptogenesis, can prevent structural damages in the hippocampal circuits, and the imprinting both of neural epileptic activity and inflammatory glial states. We performed calcium imaging of spontaneous circuits dynamics in organotypic hippocampal slices previously exposed to hyper-excitable conditions through the blockage of GABAergic synaptic transmission. Epileptogenic conditions lead to imprinted epileptic dynamics in the circuits in terms of higher frequency of neuronal firing and circuits synchronizations, higher correlated activity in neuronal pairs and decreased complexity in synchronization patterns. Acute inhibition of the STAT3-phosphorylation during epileptogenesis, prevented the imprinting of epileptic activity patterns, general cell loss, GABAergic cells loss and the persistence of inflammatory reactive glial states. This work provides further evidence that inhibiting the STAT3 signaling pathway under epileptogenesis can prevent patho-topological reorganization of neuro-glial circuits.

GABAA receptor (GABAAR) - mediated inhibition participates in the control of cortical excitability, and its impairment likely contributes to the pathologic excitability changes that have been associated with multiple neurological disorders. Therefore, there is a need for its direct evaluation in the human brain, and the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) might represent the optimal tool. TMS-evoked brain potentials (TEPs) capture the spread of activity across the stimulated brain network, and since this process at least partially depends on the GABAAR-mediated inhibition, TEPs may constitute relevant biomarkers of local GABAAergic function. Here, we aimed to assess the effect of GABAARs activation using TEPs, and to identify TEP components that are sensitive to the state of GABAAergic inhibition. In 20 healthy subjects, we recorded TEPs evoked by sub- and supra-threshold stimulation of the primary motor cortex (M1), motor-evoked potentials (MEPs) and resting-state EEG (RS-EEG). GABAARs were activated (1) pharmacologically by oral administration of alprazolam compared to placebo within each subject, and (2) physiologically using a sub-threshold conditioning stimulus to characterize the effect of short-latency intracortical inhibition (SICI). In supra-threshold TEPs, alprazolam suppressed the amplitude of components N17, N100 and P180, and increased component N45. The pharmacological modulation of N17 correlated with the change observed in MEPs and with the alprazolam-induced increase of lower {beta}-band RS-EEG. Only a reduction of N100 and P180 was found in sub-threshold TEPs. TEP SICI manifested as a reduction of N17, P60 and N100, and its effect on N17 correlated with the alprazolam-induced N17 suppression and {beta} increase. Our results indicate that N17 of supra-threshold TEPs could serve as a non-invasive biomarker of local cortical excitability reflecting the state of GABAAR-mediated inhibition in the sensorimotor network. Furthermore, the alprazolam-induced increase of {beta}-band oscillations possibly corresponds to the increased inhibitory neurotransmission within this network.

Rhythmic brain activity has been implicated in many brain functions and it is sensible to neuromodulation, but so far very few studies have investigated this activity on the cellular level in vitro in human tissue samples. In this study we revealed and characterized a novel rhythmic network activity in human neocortex. Intracellular patch-clamp recordings showed that giant depolarizing potentials (GDPs) were frequently found in human cortical neurons. GDPs appeared in a low frequency band ([~] 0.3 Hz) similar to that described for slow oscillations in vivo and displayed large amplitudes and long decay times. Under the same experimental conditions, no rhythmic activity was found in L2/3 of the rat neocortex. GDPs were predominantly observed in a subset of L2/3 interneurons considered to be large basket cells based on previously described morphological features. In addition, GDPs are highly sensitive to norepinephrine (NE) and acetylcholine (ACh), two neuromodulators known to modulate low frequency oscillations. NE increased the frequency of the GDPs by enhancing {beta}-adrenergic receptor activity while ACh decreased GDP frequency through M4 muscarinic receptor-activation. Multi-electrode array (MEA) recordings demonstrated that NE promoted synchronous oscillatory network activity while the application of ACh led to a desynchronization of neuronal activity. Our data indicate that the human neocortex is more prone to generate slow wave activity, which was reflected by more pronounced GDPs in L2/3 large basket cells. The distinct modulation of GDPs and slow wave activity by NE and ACh exerts a specific modulatory control over the human neocortex.

BackgroundDeep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been preliminarily investigated as a potential treatment for dementia. The degeneration of NBM cholinergic neurons is a pathological feature of many forms of dementia. Although stimulation of the NBM has been demonstrated to improve learning, the ideal parameters for NBM stimulation have not been elucidated. This study assesses the differential effects of varying stimulation patterns and duration on learning in a dementia rat model. Methods192-IgG-saporin (or vehicle) was injected into the NBM to produce dementia in rats. Next, all rats underwent unilateral implantation of a DBS electrode in the NBM. The experimental groups consisted of i-normal, ii-untreated demented, and iii-demented rats receiving NBM DBS. The stimulation paradigms included testing different modes (tonic and burst) and durations (1-hr, 5-hrs, and 24-hrs/day) over 10 daily sessions. Memory was assessed pre- and post-stimulation using two established learning paradigms: novel object recognition (NOR) and auditory operant chamber learning. ResultsBoth normal and stimulated rats demonstrated improved performance in NOR and auditory learning as compared to the unstimulated demented group. The burst stimulation groups performed better than the tonic stimulated group. Increasing the daily stimulation duration to 24-hr did not further improve cognitive performance in an auditory recognition task and degraded the results on a NOR task as compared with 5-hr. ConclusionThe present findings suggest that naturalistic NBM burst DBS may offer a potential effective therapy for treating dementia and suggests potential strategies for the reevaluation of current human NBM stimulation paradigms.

Acquired epilepsies, characterized by abnormal increase in hypersynchronous network activity, can be precipitated by various factors including brain injuries which cause neuronal loss and increases in network excitability. Electrical coupling between neurons, mediated by gap junctions, has been shown to enhance synchronous neuronal activity and promote excitotoxic neurodegeneration. Consequently, neuronal gap junctional coupling has been proposed to contribute to development of epilepsy. Parvalbumin expressing interneurons (PV-INs), noted for their roles in powerful perisomatic inhibition and network oscillations, have gap junctions formed exclusively by connexin 36 subunits which show changes in expression following seizures, and in human and experimental epilepsy. However, only a fraction of the connexin hemichannels form functional connections, leaving open the critical question of whether functional gap junctional coupling between neurons is altered during development of epilepsy. Using a pilocarpine induced status epilepticus (SE) model of acquired temporal lobe epilepsy in rat, this study examined changes in electrical coupling between PV-INs in the hippocampal dentate gyrus one week after SE. Contrary to expectations, SE selectively reduced the probability of electrical coupling between PV-INs without altering coupling coefficient. Both coupling frequency and coupling coefficient between non-parvalbumin interneurons remained unchanged after SE. The early and selective decrease in functional electrical coupling between dentate PV-INs after SE may represent a compensatory mechanism to limit excitotoxic damage of fast-spiking interneurons and network synchrony during epileptogenesis.

BackgroundFragile X syndrome (FXS) is the leading monogenic cause of Autism. No broadly effective support option currently exists for FXS, and drug development has suffered many failures in clinical trials based on promising preclinical findings. Thus, effective translational biomarkers of treatment outcomes are needed. Recently, electroencephalography (EEG) has been proposed as a translational biomarker in FXS. Recent years have seen an exciting emergence of novel EEG signal analyses from FXS patients. However, there is a notable gap in corresponding analyses conducted on animal models of the disorder. Being X-linked, FXS is more prevalent in males than females, and there exist significant phenotype differences between males and females with FXS. Recent studies involving male FXS participants and rodent models have identified an increase in absolute gamma EEG power, while alpha power is found to be either decreased or unchanged. However, there is not enough research on female FXS patients or models. In addition, studying EEG activity in both young and adult FXS patients or rodent models is crucial for better understanding of the disorders effects on brain development. Therefore, using the well established fmr1 knockout (KO) mouse model of FXS, we aim to compare EEG signal between female wild-type (WT) and female model mice at both juvenile and adult ages. MethodsFrontal-parietal differential EEG was recorded using a stand-alone Open-Source Electrophysiology Recording system for Rodents (OSERR). EEG activity was recorded in three different conditions: a) in the subjects home cage, and in the arenas for b) light -dark test and c) open field test. Absolute and relative EEG power as well as peak alpha frequency, theta-beta ratio, phase-amplitude and amplitude-amplitude coupling, and EEG signal complexity were computed for each condition. ResultsIn our study, we found absolute alpha, beta, gamma and total EEG power is increased in the female model compared to WT controls at the juvenile and adult ages. Alongside, relative theta power is decreased in the model. Additionally, phase-amplitude and amplitude-amplitude coupling is altered in the model. Furthermore, peak alpha frequency is increase, and theta-beta ratio is decreased in the model. Lastly, no change in EEG signal complexity is found. Discussion and ConclusionConsistent with most findings from FXS patients and rodent models, our results demonstrated an increase in gamma power in fmr1KO female mice, reinforcing gamma power as a robust and reliable EEG phenotype across FXS models. Additionally, theta-gamma cross frequency amplitude coupling is inversely coupled in female FXS model, which is similar to what has been reported in FXS patients. Overall, our findings reveal that not all EEG biomarkers observed in FXS patients are replicated in the female FXS model. For example, peak alpha frequency, theta-beta ratio, and brain signal complexity showed discrepancies between the mouse models and FXS patients. Additionally, when compared to previously reported EEG changes in male FXS mouse models, our results highlight the presence of a potential sex-based difference in EEG phenotypes at both juvenile and adult stages of fmr1 KO mouse models. Together, our study indicates that certain EEG parameters may be more translatable between rodent models and FXS patients than others and underscore the importance of considering sex and developmental stage as a critical factor when using EEG as a biomarker in FXS research.

The neurobiological basis of ADHD and its subtypes remains unclear, with inconsistent findings from studies using electrophysiology and neuroimaging. Some studies suggest ADHD-I is a distinct disorder, but there is also evidence of similar neural basis in ADHD-I and ADHD-C subtypes. This study investigates the neural basis of ADHD and its subtypes using a subnetwork modularity approach based on graph theoretical analysis of EEG data from 35 children aged 7-11. EEG was recorded in the eyes open condition and preprocessed. After preprocessing, data was analyzed using LORETA algorithm to estimate current densities in 84 regions of interest (ROIs) in the cortex and calculate functional connectivity between these ROIs in different EEG frequency bands. Then, we evaluated modularity of five functional brain networks (default mode, central control, salience, visual, and sensorimotor) using Newman modularity algorithm. Further, we evaluated edge betweenness centrality to assess communications between these functional brain networks. The study found that different brain networks have modularity in certain frequency bands, and ADHD groups showed reduced modularity of the visual network compared to normal groups in the alpha1 band (8-10 Hz). The communication between the visual network and other brain networks, except the salience network, was also reduced in ADHD groups (in the alpha1 band). However, there were no significant differences in the modularity of brain networks and communication among them between two ADHD subtypes. The results suggest a novel mechanism for ADHD involving lower intrinsic modularity in the visual network, disturbed communication between the visual network and other networks, and potential impact on the function of control and sensorimotor networks. Further, our results suggest that there may be a common neural basis for both subtypes, involving a shared disturbance in the modularity and connectivity of the ventral network. This supports the idea that ADHD-I and ADHD-C are subtypes within the same category and contradicts previous studies that suggest they are separate disorders.

Neuronal in vitro cultures are pivotal for studying brain electrophysiological function and dysfunction. Neuronal activity and communication are regulated by extracellular ion concentrations. Therefore, cell culture medium ion concentrations should ideally mimic those of cerebrospinal fluid (CSF) - considered as the milieu for brain cells in vivo. In this study, we demonstrate that commonly used cell culture media, including Neurobasal (+/- A), Neurobasal Plus, and BrainPhys media, do not accurately replicate human CSF ion concentrations. Using human iPSC-derived neuronal networks on microelectrode arrays, we show that the abnormally high potassium concentrations present in all tested cell culture media induce acute epileptiform activity, similar to that elicited by the convulsive drug 4- aminopyridine. These findings raise a critical question: How can human in vitro neuronal activity be defined as physiological and reliably distinguished from pathophysiological activity, if the routinely used ion concentrations in in vitro experiments are causing aberrant neuronal activity? SummaryThe neuronal activity in neuronal in vitro culture relies on extracellular ion concentrations, which should mimic cerebrospinal fluid (CSF). This study shows that common cell culture media and widely used artificial CSF composition in neuroscience research fail to replicate CSF ion levels, causing non-physiological and rather pathological neuronal activity.

Alzheimers disease (AD) is a multifactorial disorder that affects cognitive functioning, behavior, and neuronal properties. The neuronal dysfunction is primarily responsible for cognitive decline in AD patients, with many causal factors including plaque accumulation of A{beta}42. Neural hyperactivity induced by A{beta}42 deposition cause abnormalities in neural networks, leading to alterations in synaptic activity and interneuron dysfunction. Even though neuroimaging techniques elucidated the underlying mechanism in the neural connectivity, precise understanding in cellular level is still elusive. Previously, a few multielectrode array studies examined the neuronal network modulation in vitro cultures revealing relevance of ion channels and the chemical modulators in the presence of A{beta}42. In this study, we investigated neuronal connectivity and dynamic changes with high density multielectrode array, particularly in relation to network-wide parameter changes over time. By comparing the neuronal network between normal and A{beta}42 treated neuronal cultures, it was possible to discover the direct pathological effect of the A{beta}42 oligomer altering the network characteristics. The application of graph theory and center of activity trajectory analysis assessed the consolidation and disassociation of neural networks under A{beta}42 oligomer exposure over time. This result can enhance our understanding of how neural networks are affected during AD progression.

Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show the anterior cingulate cortex, perirhinal cortex, and cerebellum of male and female MMPs, are structurally asymmetrical. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. The anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal lobe exhibited distinct patterns of cortical gyration between left and right side. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry.

Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in the brain. The role of this growth factor in neuronal plasticity, in health and disease, has been extensively studied. However, mechanisms of epigenetic regulation of Bdnf gene expression in epilepsy are still elusive. In our previous work, using a rat model of neuronal activation upon kainate-induced seizures, we observed a repositioning of Bdnf alleles from the nuclear periphery towards the nuclear center. This change of Bdnf intranuclear position was associated with transcriptional gene activity. In the present study, using the same neuronal activation model, we analyzed the relation between the percentage of the Bdnf allele at the nuclear periphery and clinical and morphological traits of epilepsy. We observed that the decrease of the percentage of the Bdnf allele at the nuclear periphery correlates with stronger mossy fiber sprouting - an aberrant form of excitatory circuits formation. Moreover, using in vitro hippocampal cultures we showed that Bdnf repositioning is a consequence of the transcriptional activity. Inhibition of RNA polymerase II activity in primary cultured neurons with Actinomycin D completely blocked Bdnf gene transcription and repositioning observed after neuronal excitation. Interestingly, we observed that histone deacetylases inhibition with Trichostatin A induced a slight increase of Bdnf gene transcription and its repositioning even in the absence of neuronal excitation. Presented results provide novel insight into the role of BDNF in epileptogenesis. Moreover, they strengthen the statement that this particular gene is a good candidate to search for a new generation of antiepileptic therapies.

Synchrony of oscillatory brain activity has been postulated to be a binding mechanism for cognitive and motor functions. Spectral analysis of human electrocorticogram (ECoG) in sensorimotor cortex has shown that power density of gamma band activity (30-60 Hz) increased and that of alpha-beta band activity (10-20 Hz) decreased during performance of manipulative visuomotor tasks, indicating that amplitude modulation of the gamma band activity occurred in relation to the task performance. Amplitude modulation may provide evidence for synchrony of local neuronal assembly. However, it does not implement the binding mechanisms for distributed networks that are necessary for cognitive and motor functions. To prove that oscillatory activity mediates a binding mechanism, phase modulation of oscillatory activity in a wide range area should be shown. We performed coherence analysis of the ECoG signals in sensorimotor cortex to study if synchrony of the gamma band activity between these areas occurs in relation to manipulative task performance. The ECoGs were recorded from 14 sites in sensorimotor cortex including hand-arm areas with subdural grid electrodes in four subjects. Coherence estimates in all pair-wise sites were calculated in different frequency bands with 10 Hz widths from 10 to 80 Hz. In all subjects, coherence estimates increased in the lower gamma band (20-50 Hz) during the performance of the manipulative tasks. But coherence in the alpha-beta band (10-20 Hz) also increased even though amplitude modulation did not occur in this frequency band. Coherence estimates increased in site pairs within and between sensory and motor areas, many separated by intervening sites. This interregional synchrony of the alpha-beta and the lower gamma activities may play a role in integration of sensorimotor information. Task-dependent increases in coherence estimates, i.e., greater increases during performance of the manipulative tasks than during the simple tasks, suggest another role of synchrony in attention mechanism. Time-series coherence analysis showed that phase modulation occurred in different timings for activities in the alpha-beta and the lower gamma bands. For the activity in higher gamma band (50-80 Hz), power density increased but coherence estimates decreased. Thus, only amplitude modulation occurred in this frequency band. Altogether these results suggest that oscillatory activities in different frequency bands may reflect different functional roles by modulating neural activity in different ways.

The main challenge in the clinical assessment of Psychogenic Non-Epileptic Seizures (PNES) is the lack of an electroencephalographic marker in the electroencephalography (EEG) readout. Although decades of EEG studies have focused on detecting cortical brain function underlying PNES, the principle of PNES remains poorly understood. To address this problem, electric potentials generated by large populations of neurons were collected during the resting state to be processed after that by Power Spectrum Density (PSD) for possible analysis of PNES signatures. Additionally, the integration of distributed information of regular and synchronized multi-scale communication within and across inter-regional brain areas has been observed using functional connectivity tools like Phase Lag Index (PLI) and graph-derived metrics. A cohort study of 20 PNES and 19 Healthy Control subjects (HC) were enrolled. The major finding is that PNES patients exhibited significant differences in alpha-power spectrum in brain regions related to cognitive operations, attention, working memory, and movement regulation. Noticeably, we observed that there exists an altered oscillatory activity and a widespread inter-regional phase desynchronization. This indicates changes in global efficiency, node betweenness, shortest path length, and small worldness in the delta, theta, alpha, and beta frequency bands. Finally, our findings look into new evidence of the intrinsic organization of functional brain networks that reflects a dysfunctional level of integration of local activity across brain regions, which can provide new insights into the pathophysiological mechanisms of PNES.

Agrammatic aphasia is an acquired language disorder characterized by slow, non-fluent speech that include primarily content words. It is well-documented that people with agrammatism (PWA) have difficulty with production of verbs and verb morphology, but it is unknown whether these deficits occur at the single word-level, or are the result of a sentence-level impairment. The first aim of this paper is to determine the linguistic level that verb morphology impairments exist at by using magnetoencephalography (MEG) scanning to analyze neural response to two language tasks (one word-level, and one sentence-level). It has also been demonstrated that PWA benefit from a morphosemantic intervention for verb morphology deficits, but it is unknown if this therapy induces neuroplastic changes in the brain. The second aim of this paper is to determine whether or not neuroplastic changes occur after treatment, and explore the neural mechanisms by which this improvement occurs.