Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

Differential effects of haloperidol on neural oscillations during wakefulness and sleep.

The electrical activity of the brain, characterized by its frequency components, reflects a complex interplay between periodic (oscillatory) and aperiodic components. These components are associated with various neurophysiological processes, such as the excitation-inhibition balance (aperiodic activity) or interregional communication (oscillatory activity). However, we do not fully understand whether these components are truly independent or if different neuromodulators affect them in different ways. The dopaminergic system has a critical role for cognition and motivation, being a potential modulator of these power spectrum components. To improve our understanding of these questions, we investigated the differential effects of this system on these components using electrocorticogram recordings in cats, which show clear oscillations and aperiodic 1/f activity. Specifically, we focused on the effects of haloperidol (a D2 receptor antagonist) on oscillatory and aperiodic dynamics during wakefulness and sleep. By parameterizing the power spectrum into these two components, our findings reveal a robust modulation of oscillatory activity by the D2 receptor across the brain. Surprisingly, aperiodic activity was not significantly affected and exhibited inconsistent changes across the brain. This suggests a nuanced interplay between neuromodulation and the distinct components of brain oscillations, providing insights into the selective regulation of oscillatory dynamics in awake states.

Dexamethasone attenuates low-frequency brainwave disturbances following acute seizures induced by pentylenetetrazol in Wistar rats.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Brain connectivity analysis in preictal phases of seizure induced by pentylenetetrazol in rats.

Abnormal patterns of brain connectivity characterize epilepsy. However, little is known about these patterns during the stages preceding a seizure induced by pentylenetetrazol (PTZ). To investigate brain connectivity in male Wistar rats during the preictal phase of PTZ-induced seizures (60 mg/kg), we recorded local field potentials in the primary motor (M1) cortex, the ventral anterior (VA) nucleus of the thalamus, the hippocampal CA1 area, and the dentate gyrus (DG) during the baseline period and after PTZ administration. While there were no changes in power density between the baseline and preictal periods, we observed an increase in directional functional connectivity in theta from the hippocampal formation to M1 and VA, as well as in middle gamma from DG to CA1 and from CA1 to M1, and also in slow gamma from M1 to CA1. These findings are supported by increased phase coherence between DG-M1 in theta and CA1-M1 in middle gamma, as well as enhanced phase-amplitude coupling of delta-middle gamma in M1 and delta-fast gamma in CA1. Interestingly, we also noted a slight decrease in phase synchrony between CA1 and VA in slow gamma. Together, these results demonstrate increased functional connectivity between brain regions during the PTZ-induced preictal period, with this increase being particularly driven by the hippocampal formation.

An appraisal to Hans Berger by the time of his 150th birthday: the human EEG and tales of blood flow, heat and brain waves.

More than 100 years of research have passed by and still the human electroencephalogram (EEG) remains a puzzle to be solved. Starting from his studies on plethysmography until his theories on brain thermodynamics, Hans Berger was able to refine his method of recording cortical signs with the apparatus at his disposal in an ordinary neuropsychiatric yard towards an early account of human EEG. This review is an appraisal of his contribution to the field of modern neurophysiology.

Mais de 100 anos se passaram e o eletroencefalograma humano (EEG) continua sendo um enigma a ser desvendado. A partir de seus estudos sobre pletismografia até suas teorias sobre termodinâmica cerebral, Hans Berger conseguiu refinar seu método de registro da atividade elétrica cortical com os equipamentos a sua disposição em uma ala psiquiátrica comum produzindo uma descrição acurada do EEG humano. Esta revisão é um breve resumo de sua contribuição para o campo da neurofisiologia moderna.

Effect of reward and punishment on no-risk decision-making in young men: An EEG study.

Decision-making is a process that allows adapting behavior in response to feedback to achieve a goal. Previous studies have suggested that the cerebral cortex shows different activation patterns in response to feedback. However, the effects of reward and punishment on learning contexts and decision-making are not clear. Thus, this experiment compared the effects of reward and punishment on behavior and the electroencephalographic activity of cortical areas related to decision-making in a no-risk context. Twenty healthy males were asked to perform a decision-making task under two conditions in which the goal was to finish in the shortest time possible. In the reward condition, the more points the participant accumulated the sooner the task ended, while in the punishment condition, the more points accumulated the longer the task lasted. Lower reaction times were found in the reward condition, characterized by a higher absolute power of the slow bands in almost all the cortices recorded. Changes in the interhemispheric correlation were also obtained in the comparison of the two feedback conditions. Results suggest that changes in the type of feedback affect cortical functionality and behavioral execution during decision-making, with the reward being related to a quick emotional response strategy and punishment associated with slower and, likely, more reasoned responses.

Spectral Power Density analysis of the resting-state as a marker of the central effects of opioid use in fibromyalgia.

Spectral power density (SPD) indexed by electroencephalogram (EEG) recordings has recently gained attention in elucidating neural mechanisms of chronic pain syndromes and medication use. We compared SPD variations between 15 fibromyalgia (FM) women in use of opioid in the last three months (73.33% used tramadol) with 32 non-users. EEG data were obtained with Eyes Open (EO) and Eyes Closed (EC) resting state. SPD peak amplitudes between EO-EC were smaller in opioid users in central theta, central beta, and parietal beta, and at parietal delta. However, these variations were positive for opioid users. Multivariate analyses of variance (ANOVAs) revealed that EO-EC variations in parietal delta were negatively correlated with the disability due to pain, and central and parietal beta activity variations were positively correlated with worse sleep quality. These clinical variables explained from 12.5 to 17.2% of SPD variance. In addition, central beta showed 67% sensitivity / 72% specificity and parietal beta showed 73% sensitivity/62% specificity in discriminating opioid users from non-users. These findings suggest oscillations in EEG might be a sensitive surrogate marker to screen FM opioid users and a promising tool to understand the effects of opioid use and how these effects relate to functional and sleep-related symptoms.

Early NMDA Receptor Ablation in Interneurons Causes an Activity-Dependent E/I Imbalance in vivo in Prefrontal Cortex Pyramidal Neurons of a Mouse Model Useful for the Study of Schizophrenia.

Altered Excitatory/Inhibitory (E/I) balance of cortical synaptic inputs has been proposed as a central pathophysiological factor for psychiatric neurodevelopmental disorders, including schizophrenia (SZ). However, direct measurement of E/I synaptic balance have not been assessed in vivo for any validated SZ animal model. Using a mouse model useful for the study of SZ we show that a selective ablation of NMDA receptors (NMDAr) in cortical and hippocampal interneurons during early postnatal development results in an E/I imbalance in vivo, with synaptic inputs to pyramidal neurons shifted towards excitation in the adult mutant medial prefrontal cortex (mPFC). Remarkably, this imbalance depends on the cortical state, only emerging when theta and gamma oscillations are predominant in the network. Additional brain slice recordings and subsequent 3D morphological reconstruction showed that E/I imbalance emerges after adolescence concomitantly with significant dendritic retraction and dendritic spine re-localization in pyramidal neurons. Therefore, early postnatal ablation of NMDAr in cortical and hippocampal interneurons developmentally impacts on E/I imbalance in vivo in an activity-dependent manner.

The Effects of Neurofeedback on Aging-Associated Cognitive Decline: A Systematic Review.

For more than a decade, neurofeedback interventions have been applied with the goal of improving cognitive functions in older adults. Some of these studies have been reviewed, but only in combination with experiments conducted in young adults or with studies seeking to modify functions not related to cognition. The purpose of the present review is to assess whether neurofeedback interventions benefit cognition in elderly adults. We included all neurofeedback studies conducted in older adults, whether healthy or affected by a clinical condition, that attempted to ameliorate any domain of cognition, with no restrictions by publication date. Fourteen studies were eligible for this review. Neurofeedback improved memory in healthy and unhealthy participants mainly when the theta and sensorimotor rhythm (SMR) frequencies were trained. In addition, other cognitive domains benefited from this intervention. Conversely, neurofeedback had no effect on attention processes. Although different studies used markedly different methods, almost all of them reported positive effects of neurofeedback in at least one cognitive domain. New interventions under consideration should be tested using placebo-controlled, double-blind experimental designs with follow-up evaluations.

New insights on the ventral attention network: Active suppression and involuntary recruitment during a bimodal task.

Detection of unexpected, yet relevant events is essential in daily life. fMRI studies have revealed the involvement of the ventral attention network (VAN), including the temporo-parietal junction (TPJ), in such process. In this MEG study with 34 participants (17 women), we used a bimodal (visual/auditory) attention task to determine the neuronal dynamics associated with suppression of the activity of the VAN during top-down attention and its recruitment when information from the unattended sensory modality is involuntarily integrated. We observed an anticipatory power increase of alpha/beta oscillations (12-20 Hz, previously associated with functional inhibition) in the VAN following a cue indicating the modality to attend. Stronger VAN power increases were associated with better task performance, suggesting that the VAN suppression prevents shifting attention to distractors. Moreover, the TPJ was synchronized with the frontal eye field in that frequency band, indicating that the dorsal attention network (DAN) might participate in such suppression. Furthermore, we found a 12-20 Hz power decrease and enhanced synchronization, in both the VAN and DAN, when information between sensory modalities was congruent, suggesting an involvement of these networks when attention is involuntarily enhanced due to multisensory integration. Our results show that effective multimodal attentional allocation includes the modulation of the VAN and DAN through upper-alpha/beta oscillations. Altogether these results indicate that the suppressing role of alpha/beta oscillations might operate beyond sensory regions.

Acute Effects of Two Different Species of Amyloid-ß on Oscillatory Activity and Synaptic Plasticity in the Commissural CA3-CA1 Circuit of the Hippocampus.

Recent evidence indicates that soluble amyloid-ß (Aß) species induce imbalances in excitatory and inhibitory transmission, resulting in neural network functional impairment and cognitive deficits during early stages of Alzheimer's disease (AD). To evaluate the in vivo effects of two soluble Aß species (Aß 25-35 and Aß 1-40) on commissural CA3-to-CA1 (cCA3-to-CA1) synaptic transmission and plasticity, and CA1 oscillatory activity, we used acute intrahippocampal microinjections in adult anaesthetized male Wistar rats. Soluble Aß microinjection increased cCA3-to-CA1 synaptic variability without significant changes in synaptic efficiency. High-frequency CA3 stimulation was rendered inefficient by soluble Aß intrahippocampal injection to induce long-term potentiation and to enhance synaptic variability in CA1, contrasting with what was observed in vehicle-injected subjects. Although soluble Aß microinjection significantly increased the relative power of γ-band and ripple oscillations and significantly shifted the average vector of θ-to-γ phase-amplitude coupling (PAC) in CA1, it prevented θ-to-γ PAC shift induced by high-frequency CA3 stimulation, opposite to what was observed in vehicle-injected animals. These results provide further evidence that soluble Aß species induce synaptic dysfunction causing abnormal synaptic variability, impaired long-term plasticity, and deviant oscillatory activity, leading to network activity derailment in the hippocampus.

Modulation in phase and frequency of neural oscillations during epileptiform activity induced by neonatal Zika virus infection in mice.

Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZIKV) infection. Through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. The index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. Furthermore, by comparing ZIKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.

Effects of mindfulness on psychological and psychophysiological responses during self-paced walking.

The aim of the present study was to investigate the effects of an audio-guided mindfulness (MF) single session on psychological and psychophysiological responses during an outdoor walking task. Twenty-four participants (12 females and 12 males; Mage  = 23.6, SD = 3.9 years) were required to walk 200 m at a pace of their choosing. Two experimental conditions (mindfulness meditation and mindlessness [ML] meditation) and a control condition (CO) were administered. Electrical activity in the brain was measured by the use of a portable electroencephalography (EEG) system during walking. Fast Fourier Transform was used to decompose the EEG samples into theta (5-7 Hz), alpha (8-14 Hz), and beta (15-29 Hz) frequencies. Brain connectivity analysis between frontal and temporo-parietal electrode sites was conducted to explore functional interactions through the use of spectral coherence. Affective and perceptual responses were measured by the use of single-item scales and questionnaires. The present findings indicate that MF was sufficiently potent to reallocate attention toward task-related thoughts, downregulate perceived activation, and enhance affective responses to a greater degree than the other two conditions. Conversely, ML was sufficient to increase the use of dissociative thoughts, make participants less aware of their physical sensations and emotions, induce a more negative affective state, and upregulate perceived activation to a greater extent than MF and CO. The brain mechanisms that underlie the effects of MF on exercise appear to be associated with the enhanced inter-hemispheric connectivity of high-frequency waves between right frontal and left temporo-parietal areas of the cortex.

Task-specific signatures in the expert brain: Differential correlates of translation and reading in professional interpreters.

Insights on the neurocognitive particularities of expert individuals have benefited from language studies on professional simultaneous interpreters (PSIs). Accruing research indicates that behavioral advantages in this population are restricted to those skills that are directly taxed during professional practice (e.g., translation as opposed to reading), but little is known about the neural signatures of such selective effects. To illuminate the issue, we recruited 17 PSIs and 15 non-interpreter bilinguals and compared behavioral and electrophysiological markers of word reading and translation from and into their native and non-native languages (L1 and L2, respectively). PSIs exhibited greater delta-theta (1-8 â€‹Hz) power across all tasks over varying topographies, but these were accompanied by faster performance only in the case of translation conditions. Moreover, neural differences in PSIs were most marked for L2-L1 translation (the dominant interpreting direction in their market), which exhibited maximally widespread modulations that selectively correlated with behavioral outcomes. Taken together, our results suggest that interpreting experience involves distinct neural signatures across reading and translation mechanisms, but that these are systematically related with processing efficiency only in domains that face elevated demands during everyday practice (i.e., L2-L1 translation). These findings can inform models of simultaneous interpreting, in particular, and expert cognitive processing, in general.

Oscilopatología en Trastornos del Espectro Autista / Oscillopathology in Autist Spectrum Disorder

Language as a vehicle for human development has an important impact on social processes which are decisive in the establishment of optimal living conditions. Modern studies have found that skills that make of language an activity of complex multisensory integration are determined by the oscillation rhythms of the different brain waves described from neurosciences. In the literature has described an abnormal pattern of oscillations, responsible for communicative deficiencies in individuals with Autist Spectrum Disorders and beside with social deficits, resulting in a typically characteristic profile. Brain waves show an impact on the mental states that be high cognitive demand as learning, communication and speech understanding, widespread difficulties in this population. The recent findings presented here and product of a judicious bibliographic review, are characterized within speech therapy making it possible to land the intervention processes to the linguistic and cognitive needs of these individuals, using biological mechanisms and resulting in possible procedures of greater relevance and effectiveness, that improve user's life quality and motivate speech therapy and similar professionals to expand their knowledge in this interesting field.

Brain Arrhythmias Induced by Amyloid Beta and Inflammation: Involvement in Alzheimer's Disease and Other Inflammation-related Pathologies.

A variety of neurological diseases, including Alzheimer's disease (AD), involve amyloid beta (Aß) accumulation and/or neuroinflammation, which can alter synaptic and neural circuit functions. Consequently, these pathological conditions induce changes in neural network rhythmic activity (brain arrhythmias), which affects many brain functions. Neural network rhythms are involved in information processing, storage and retrieval, which are essential for memory consolidation, executive functioning and sensory processing. Therefore, brain arrhythmias could have catastrophic effects on circuit function, underlying the symptoms of various neurological diseases. Moreover, brain arrhythmias can serve as biomarkers for a variety of brain diseases. The aim of this review is to provide evidence linking Aß and inflammation to neural network dysfunction, focusing on alterations in brain rhythms and their impact on cognition and sensory processing. I reviewed the most common brain arrhythmias characterized in AD, in AD transgenic models and those induced by Aß. In addition, I reviewed the modulations of brain rhythms in neuroinflammatory diseases and those induced by immunogens, interleukins and microglia. This review reveals that Aß and inflammation produce a complex set of effects on neural network function, which are related to the induction of brain arrhythmias and hyperexcitability, both closely related to behavioral alterations. Understanding these brain arrhythmias can help to develop therapeutic strategies to halt or prevent these neural network alterations and treat not only the arrhythmias but also the symptoms of AD and other inflammation-related pathologies.

Bifurcation structure determines different phase-amplitude coupling patterns in the activity of biologically plausible neural networks.

Phase-amplitude cross frequency coupling (PAC) is a rather ubiquitous phenomenon that has been observed in a variety of physical domains; however, the mechanisms underlying the emergence of PAC and its functional significance in the context of neural processes are open issues under debate. In this work we analytically demonstrate that PAC phenomenon naturally emerges in mean-field models of biologically plausible networks, as a signature of specific bifurcation structures. The proposed analysis, based on bifurcation theory, allows the identification of the mechanisms underlying oscillatory dynamics that are essentially different in the context of PAC. Specifically, we found that two PAC classes can coexist in the complex dynamics of the analyzed networks: 1) harmonic PAC which is an epiphenomenon of the nonsinusoidal waveform shape characterized by the linear superposition of harmonically related spectral components, and 2) nonharmonic PAC associated with "true" coupled oscillatory dynamics with independent frequencies elicited by a secondary Hopf bifurcation and mechanisms involving periodic excitation/inhibition (PEI) of a network population. Importantly, these two PAC types have been experimentally observed in a variety of neural architectures confounding traditional parametric and nonparametric PAC metrics, like those based on linear filtering or the waveform shape analysis, due to the fact that these methods operate on a single one-dimensional projection of an intrinsically multidimensional system dynamics. We exploit the proposed tools to study the functional significance of the PAC phenomenon in the context of Parkinson's disease (PD). Our results show that pathological slow oscillations (e.g. ß band) and nonharmonic PAC patterns emerge from dissimilar underlying mechanisms (bifurcations) and are associated to the competition of different BG-thalamocortical loops. Thus, this study provides theoretical arguments that demonstrate that nonharmonic PAC is not an epiphenomenon related to the pathological ß band oscillations, thus supporting the experimental evidence about the relevance of PAC as a potential biomarker of PD.

Delayed creatine supplementation counteracts reduction of GABAergic function and protects against seizures susceptibility after traumatic brain injury in rats.

Traumatic brain injury (TBI) is a devastating disease frequently followed by behavioral disabilities including post-traumatic epilepsy (PTE). Although reasonable progress in understanding its pathophysiology has been made, treatment of PTE is still limited. Several studies have shown the neuroprotective effect of creatine in different models of brain pathology, but its effects on PTE is not elucidated. Thus, we decided to investigate the impact of delayed and chronic creatine supplementation on susceptibility to epileptic seizures evoked by pentylenetetrazol (PTZ) after TBI. Our experimental data revealed that 4 weeks of creatine supplementation (300 mg/kg, p.o.) initiated 1 week after fluid percussion injury (FPI) notably increased the latency to first myoclonic and tonic-clonic seizures, decreased the time spent in tonic-clonic seizure, seizure intensity, epileptiform discharges and spindle oscillations induced by a sub-convulsant dose of PTZ (35 mg/kg, i.p.). Interestingly, this protective effect persists for 1 week even when creatine supplementation is discontinued. The anticonvulsant effect of creatine was associated with its ability to reduce cell loss including the number of parvalbumin positive (PARV+) cells in CA3 region of the hippocampus. Furthermore, creatine supplementation also protected against the reduction of GAD67 levels, GAD activity and specific [3H]flunitrazepam binding in the hippocampus. These findings showed that chronic creatine supplementation may play a neuroprotective role on brain excitability by controlling the GABAergic function after TBI, providing a possible new strategy for the treatment of PTE.

A hemodynamic network involving the insula, the cingulate, and the basal forebrain correlates with EEG synchronization phases of sleep instability.

The cyclic alternating pattern (CAP) encompasses the pseudoperiodic appearance of synchronized brain waves and rhythms and is considered a regulator of the nonrapid eye movement (NREM) sleep vigilance level, reflecting sleep instability. To determine the brain regions responsible for this phenomenon, we scored and analyzed sleep functional magnetic resonance imaging data acquired with simultaneous electroencephalography (EEG-fMRI). Group analysis revealed a set of brain areas showing statistically significant blood oxygen-level dependent signal correlated positively with the synchronization phase of the CAP, most prominent being the insula, the middle cingulate gyrus, and the basal forebrain. These areas may form a network acting as a synchronization pacemaker, controlling the level of NREM sleep vigilance and the sleeper's arousability.