Local contribution to the somatosensory evoked potentials in rat's thalamus.

Local Field Potential (LFP), despite its name, often reflects remote activity. Depending on the orientation and synchrony of their sources, both oscillations and more complex waves may passively spread in brain tissue over long distances and be falsely interpreted as local activity at such distant recording sites. Here we show that the whisker-evoked potentials in the thalamic nuclei are of local origin up to around 6 ms post stimulus, but the later (7-15 ms) wave is overshadowed by a negative component reaching from cortex. This component can be analytically removed and local thalamic LFP can be recovered reliably using Current Source Density analysis. We used model-based kernel CSD (kCSD) method which allowed us to study the contribution of local and distant currents to LFP from rat thalamic nuclei and barrel cortex recorded with multiple, non-linear and non-regular multichannel probes. Importantly, we verified that concurrent recordings from the cortex are not essential for reliable thalamic CSD estimation. The proposed framework can be used to analyze LFP from other brain areas and has consequences for general LFP interpretation and analysis.

PEARL-Neuro Database: EEG, fMRI, health and lifestyle data of middle-aged people at risk of dementia.

Interdisciplinary approaches are needed to understand the relationship between genetic factors and brain structure and function. Here we describe a database that includes genetic data on apolipoprotein E (APOE) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes, both of which are known to increase the risk of late-onset Alzheimer's disease, paired with psychometric (memory, intelligence, mood, personality, stress coping strategies), basic demographic and health data on a cohort of 192 healthy middle-aged (50-63) individuals. Part of the database (~79 participants) also includes blood tests (blood counts, lipid profile, HSV virus) and functional neuroimaging data (EEG/fMRI) recorded with a resting-state protocol (eyes open and eyes closed) and two cognitive tasks (multi-source interference task, MSIT; and Sternberg's memory task). The data were validated and showed overall good quality. This open-science dataset is well suited not only for research relating to susceptibility to Alzheimer's disease but also for more general questions on brain aging or can be used as part of meta-analytical multi-disciplinary projects.

Common and distinct BOLD correlates of Simon and flanker conflicts which can(not) be reduced to time-on-task effects.

The ability to identify and resolve conflicts between standard, well-trained behaviors and behaviors required by the current context is an essential feature of cognitive control. To date, no consensus has been reached on the brain mechanisms involved in exerting such control: while some studies identified diverse patterns of activity across different conflicts, other studies reported common resources across conflict tasks or even across simple tasks devoid of the conflict component. The latter reports attributed the entire activity observed in the presence of conflict to longer time spent on the task (i.e., to the so-called time-on-task effects). Here, we used an extended Multi-Source Interference Task (MSIT) which combines Simon and flanker types of interference to determine shared and conflict-specific mechanisms of conflict resolution in fMRI and their separability from the time-on-task effects. Large portions of the activity in the dorsal attention network and decreases of activity in the default mode network were shared across the tasks and scaled in parallel with increasing reaction times. Importantly, the activity in the sensory and sensorimotor cortices, as well as in the posterior medial frontal cortex (pMFC) - a key region implicated in conflict processing - could not be exhaustively explained by the time-on-task effects.

Altered granulocyte count and erythrocyte measures in middle-aged, healthy carriers of APOE and PICALM risk genes for Alzheimer's disease.

APOE­Îµ4 genotype (apolipoprotein E, epsilon 4) is the strongest genetic risk factor for Alzheimer's disease (AD). Despite years of research, it is still not known how it contributes to dementia development. APOE has been implicated in many AD pathology mechanisms, like Aß clearance, brain metabolism, changes within microglia and other glial functions and inflammatory processes. In fact, immunological/inflammatory processes are recently discussed as an important factor in Alzheimer's development and granulocyte profiles changes are reported in patients. However, the exact link between the immune system and risk­genes is unknown. In particular, it is not known whether and how they interact throughout the lifetime, before the disease onset. The aim of the study was to investigate the relationship between granulocyte count and the APOE/PICALM genes in healthy individuals with an increased genetic risk of AD. An exploratory analysis regarding other blood cells was also conducted. Blood samples were collected from 77 healthy middle­aged (50-63 years old) participants, who were also asked to complete a health and life­style questionnaires. Groups with different AD risk­genes were compared. Differences in granulocyte profiles were found in healthy carriers of AD risk­genes who had slightly elevated eosinophil levels as compared to non-risk carriers. An exploratory analysis showed some alteration in mean corpuscular hemoglobin content and concentration (MCH/MCHC) levels between risk­carriers subgroups and non-risk carriers. No other differences in blood count or lipoprotein profile were found between healthy APOE/PICALM risk­carriers and non-risk carriers. Longitudinal studies will reveal if and how those changes contribute to the development of AD pathology.

In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface.

In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain-computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today's major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

The Nencki-Symfonia electroencephalography/event-related potential dataset: Multiple cognitive tasks and resting-state data collected in a sample of healthy adults.

BACKGROUND: One of the goals of neuropsychology is to understand the brain mechanisms underlying aspects of attention and cognitive control. Several tasks have been developed as a part of this body of research, however their results are not always consistent. A reliable comparison of the data and a synthesis of study conclusions has been precluded by multiple methodological differences. Here, we describe a publicly available, high-density electroencephalography (EEG) dataset obtained from 42 healthy young adults while they performed 3 cognitive tasks: (i) an extended multi-source interference task; (ii) a 3-stimuli oddball task; (iii) a control, simple reaction task; and (iv) a resting-state protocol. Demographic and psychometric information are included within the dataset. DATASET VALIDATION: First, data validation confirmed acceptable quality of the obtained EEG signals. Typical event-related potential (ERP) waveforms were obtained, as expected for attention and cognitive control tasks (i.e., N200, P300, N450). Behavioral results showed the expected progression of reaction times and error rates, which confirmed the effectiveness of the applied paradigms. CONCLUSIONS: This dataset is well suited for neuropsychological research regarding common and distinct mechanisms involved in different cognitive tasks. Using this dataset, researchers can compare a wide range of classical EEG/ERP features across tasks for any selected subset of electrodes. At the same time, 128-channel EEG recording allows for source localization and detailed connectivity studies. Neurophysiological measures can be correlated with additional psychometric data obtained from the same participants. This dataset can also be used to develop and verify novel analytical and classification approaches that can advance the field of deep/machine learning algorithms, recognition of single-trial ERP responses to different task conditions, and detection of EEG/ERP features for use in brain-computer interface applications.

Modular Data Acquisition System for Recording Activity and Electrical Stimulation of Brain Tissue Using Dedicated Electronics.

In this paper, we present a modular Data Acquisition (DAQ) system for simultaneous electrical stimulation and recording of brain activity. The DAQ system is designed to work with custom-designed Application Specific Integrated Circuit (ASIC) called Neurostim-3 and a variety of commercially available Multi-Electrode Arrays (MEAs). The system can control simultaneously up to 512 independent bidirectional i.e., input-output channels. We present in-depth insight into both hardware and software architectures and discuss relationships between cooperating parts of that system. The particular focus of this study was the exploration of efficient software design so that it could perform all its tasks in real-time using a standard Personal Computer (PC) without the need for data precomputation even for the most demanding experiment scenarios. Not only do we show bare performance metrics, but we also used this software to characterise signal processing capabilities of Neurostim-3 (e.g., gain linearity, transmission band) so that to obtain information on how well it can handle neural signals in real-world applications. The results indicate that each Neurostim-3 channel exhibits signal gain linearity in a wide range of input signal amplitudes. Moreover, their high-pass cut-off frequency gets close to 0.6Hz making it suitable for recording both Local Field Potential (LFP) and spiking brain activity signals. Additionally, the current stimulation circuitry was checked in terms of the ability to reproduce complex patterns. Finally, we present data acquired using our system from the experiments on a living rat's brain, which proved we obtained physiological data from non-stimulated and stimulated tissue. The presented results lead us to conclude that our hardware and software can work efficiently and effectively in tandem giving valuable insights into how information is being processed by the brain.

What we can and what we cannot see with extracellular multielectrodes.

Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable. We demonstrate this in the general setting of previously proposed kernel Current Source Density method and illustrate it with simplified examples as well as using evoked potentials from the barrel cortex obtained with a Neuropixels probe and with compatible model data. We show that with conceptual separation of the estimation space from experimental setup one can recover sources not accessible to standard methods.

Cholinergic and Noradrenergic Modulation of Corticothalamic Synaptic Input From Layer 6 to the Posteromedial Thalamic Nucleus in the Rat.

Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using an in vitro slice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by "pseudominimal" stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic α-2 agonist clonidine, α-1 agonist phenylephrine, or ß-receptor agonist isoproterenol showed that the modulation may partly rely on α-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM.

Distinct circuits in rat central amygdala for defensive behaviors evoked by socially signaled imminent versus remote danger.

Animals display a rich repertoire of defensive responses adequate to the threat proximity. In social species, these reactions can be additionally influenced by the behavior of fearful conspecifics. However, the majority of neuroscientific studies on socially triggered defensive responses focuses on one type of behavior, freezing. To study a broader range of socially triggered reactions and underlying mechanisms, we directly compared two experimental paradigms, mimicking occurrence of the imminent versus remote threat. Observation of a partner currently experiencing aversive stimulation evokes passive defensive responses in the observer rats. Similar interaction with a partner that has just undergone the aversive stimulation prompts animals to increase active exploration. Although the observers display behaviors similar to those of the aversively stimulated demonstrators, their reactions are not synchronized in time, suggesting that observers' responses are caused by the change in their affective state rather than mimicry. Using opsins targeted to behaviorally activated neurons, we tagged central amygdala (CeA) cells implicated in observers' responses to either imminent or remote threat and reactivated them during the exploration of a novel environment. The manipulation revealed that the two populations of CeA cells promote passive or active defensive responses, respectively. Further experiments confirmed that the two populations of cells at least partially differ in expression of molecular markers (protein kinase C-δ [PKC-δ] and corticotropin-releasing factor [CRF]) and connectivity patterns (receiving input from the basolateral amygdala or from the anterior insula). The results are consistent with the literature on single subjects' fear conditioning, suggesting that similar neuronal circuits control defensive responses in social and non-social contexts.

Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia.

Wake-related ketamine-dependent high frequency oscillations (HFO) can be recorded in local field potentials (LFP) from cortical and subcortical regions in rodents. The mechanisms underlying their generation and occurrence in higher mammals are unclear. Unfortunately, anesthetic doses of pure ketamine attenuate HFO, which has precluded their investigation under anesthesia. Here, we show ketamine-xylazine (KX) anesthesia is associated with a prominent 80-130 Hz rhythm in the olfactory bulb (OB) of rats, whereas 30-65 Hz gamma power is diminished. Simultaneous LFP and thermocouple recordings revealed the 80-130 Hz rhythm was dependent on nasal respiration. This rhythm persisted despite surgical excision of the piriform cortex. Silicon probes spanning the dorsoventral aspect of the OB revealed this rhythm was strongest in ventral areas and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed dependency on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, a similar rhythm occurred in the OB of KX-anesthetized cats, which shared key features with our rodent studies. We conclude that the activity we report here is driven by nasal airflow, local excitatory-inhibitory interactions, and conserved in higher mammals. Additionally, KX anesthesia is a convenient model to investigate further the mechanisms underlying wake-related ketamine-dependent HFO.

Resting-state EEG activity predicts frontoparietal network reconfiguration and improved attentional performance.

Mounting evidence indicates that resting-state EEG activity is related to various cognitive functions. To trace physiological underpinnings of this relationship, we investigated EEG and behavioral performance of 36 healthy adults recorded at rest and during visual attention tasks: visual search and gun shooting. All measures were repeated two months later to determine stability of the results. Correlation analyses revealed that within the range of 2-45 Hz, at rest, beta-2 band power correlated with the strength of frontoparietal connectivity and behavioral performance in both sessions. Participants with lower global beta-2 resting-state power (gB2rest) showed weaker frontoparietal connectivity and greater capacity for its modifications, as indicated by changes in phase correlations of the EEG signals. At the same time shorter reaction times and improved shooting accuracy were found, in both test and retest, in participants with low gB2rest compared to higher gB2rest values. We posit that weak frontoparietal connectivity permits flexible network reconfigurations required for improved performance in everyday tasks.

EEG-neurofeedback training of beta band (12-22Hz) affects alpha and beta frequencies - A controlled study of a healthy population.

The frequency-function relation of various EEG bands has inspired EEG-neurofeedback procedures intending to improve cognitive abilities in numerous clinical groups. In this study, we administered EEG-neurofeedback (EEG-NFB) to a healthy population to determine the efficacy of this procedure. We evaluated feedback manipulation in the beta band (12-22Hz), known to be involved in visual attention processing. Two groups of healthy adults were trained to either up- or down-regulate beta band activity, thus providing mutual control. Up-regulation training induced increases in beta and alpha band (8-12Hz) amplitudes during the first three sessions. Group-independent increases in the activity of both bands were observed in the later phase of training. EEG changes were not matched by measured behavioural indices of attention. Parallel changes in the two bands challenge the idea of frequency-specific EEG-NFB protocols and suggest their interdependence. Our study exposes the possibility (i) that the alpha band is more prone to manipulation, and (ii) that changes in the bands' amplitudes are independent from specified training. We therefore encourage a more comprehensive approach to EEG-neurofeedback training embracing physiological and/or operational relations among various EEG bands.

Beware: Recruitment of Muscle Activity by the EEG-Neurofeedback Trainings of High Frequencies.

EEG-neurofeedback (NFB) became a very popular method aimed at improving cognitive and behavioral performance. However, the EMG frequency spectrum overlies the higher EEG oscillations and the NFB trainings focusing on these frequencies is hindered by the problem of EMG load in the information fed back to the subjects. In such a complex signal, it is highly probable that the most controllable component will form the basis for operant conditioning. This might cause different effects in the case of various training protocols and therefore needs to be carefully assessed before designing training protocols and algorithms. In the current experiment a group of healthy adults (n = 14) was trained by professional trainers to up-regulate their beta1 (15-22 Hz) band for eight sessions. The control group (n = 18) underwent the same training regime but without rewards for increasing beta. In half of the participants trained to up-regulate beta1 band (n = 7) a systematic increase in tonic EMG activity was identified offline, implying that muscle activity became a foundation for reinforcement in the trainings. The remaining participants did not present any specific increase of the trained beta1 band amplitude. The training was perceived effective by both trainers and the trainees in all groups. These results indicate the necessity of proper control of muscle activity as a requirement for the genuine EEG-NFB training, especially in protocols that do not aim at the participants' relaxation. The specificity of the information fed back to the participants should be of highest interest to all therapists and researchers, as it might irreversibly alter the results of the training.

The Do's and Don'ts of Neurofeedback Training: A Review of the Controlled Studies Using Healthy Adults.

The goal of EEG neurofeedback (EEG-NFB) training is to induce changes in the power of targeted EEG bands to produce beneficial changes in cognitive or motor function. The effectiveness of different EEG-NFB protocols can be measured using two dependent variables: (1) changes in EEG activity and (2) behavioral changes of a targeted function (for therapeutic applications the desired changes should be long-lasting). To firmly establish a causal link between these variables and the selected protocol, similar changes should not be observed when appropriate control paradigms are used. The main objective of this review is to evaluate the evidence, reported in the scientific literature, which supports the validity of various EEG-NFB protocols. Our primary concern is to highlight the role that uncontrolled nonspecific factors can play in the results generated from EEG-NFB studies. Nonspecific factors are often ignored in EEG-NFB designs or the data are not presented, which means conclusions should be interpreted cautiously. As an outcome of this review we present a do's and don'ts list, which can be used to develop future EEG-NFB methodologies, based on the small set of experiments in which the proper control groups have excluded non-EEG-NFB related effects. We found two features which positively correlated with the expected changes in power of the trained EEG band(s): (1) protocols which focused on training a smaller number of frequency bands and (2) a bigger number of electrodes used for neurofeedback training. However, we did not find evidence in support of the positive relationship between power changes of a trained frequency band(s) and specific behavioral effects.

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention.

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation.

Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus.

Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first-order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher-order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first-order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo-cortical loop. We thus demonstrate a way in which the thalamo-cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.

Retinal origin of electrically evoked potentials in response to transcorneal alternating current stimulation in the rat.

PURPOSE: Little is known about the physiological mechanisms underlying the reported therapeutic effects of transorbital alternating current stimulation (ACS) in vision restoration, or the origin of the recorded electrically evoked potentials (EEPs) during such stimulation. We examined the issue of EEP origin and electrode configuration for transorbital ACS and characterized the physiological responses to CS in different structures of the visual system. METHODS: We recorded visually evoked potentials (VEPs) and EEPs from the rat retina, visual thalamus, tectum, and visual cortex. The VEPs were evoked by light flashes and EEPs were evoked by electric stimuli delivered by two electrodes placed either together on the same eye or on the eyeball and in the neck. Electrically evoked potentials and VEPs were recorded before and after bilateral intraorbital injections of tetrodotoxin that blocked retinal ganglion cell activity. RESULTS: Tetrodotoxin abolished VEPs at all levels in the visual pathway, confirming successful blockage of ganglion cell activity. Tetrodotoxin also abolished EEPs and this effect was independent of the stimulating electrode configurations. CONCLUSIONS: Transorbital electrically evoked responses in the visual pathway, irrespective of reference electrode placement, are initiated by activation of the retina and not by passive conductance and direct activation of neurons in other visual structures. Thus, placement of stimulating electrodes exclusively around the eyeball may be sufficient to achieve therapeutic effects.

Common atlas format and 3D brain atlas reconstructor: infrastructure for constructing 3D brain atlases.

One of the challenges of modern neuroscience is integrating voluminous data of diferent modalities derived from a variety of specimens. This task requires a common spatial framework that can be provided by brain atlases. The first atlases were limited to two-dimentional presentation of structural data. Recently, attempts at creating 3D atlases have been made to offer navigation within non-standard anatomical planes and improve capability of localization of different types of data within the brain volume. The 3D atlases available so far have been created using frameworks which make it difficult for other researchers to replicate the results. To facilitate reproducible research and data sharing in the field we propose an SVG-based Common Atlas Format (CAF) to store 2D atlas delineations or other compatible data and 3D Brain Atlas Reconstructor (3dBAR), software dedicated to automated reconstruction of three-dimensional brain structures from 2D atlas data. The basic functionality is provided by (1) a set of parsers which translate various atlases from a number of formats into the CAF, and (2) a module generating 3D models from CAF datasets. The whole reconstruction process is reproducible and can easily be configured, tracked and reviewed, which facilitates fixing errors. Manual corrections can be made when automatic reconstruction is not sufficient. The software was designed to simplify interoperability with other neuroinformatics tools by using open file formats. The content can easily be exchanged at any stage of data processing. The framework allows for the addition of new public or proprietary content.