RESUMEN
A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to a subpopulation of layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to reproduce error-related spiking modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 error PCs generate theta rhythmicity with random phases. Saccades synchronized the phases of the theta-rhythm, which was magnified on errors. Contributions from error PCs to the laminar current source density (CSD) observed in SEF were negligible and could not explain the observed association between error-related spiking modulation in L3 PCs and scalp-EEG. CSD from recorded laminar field potentials in SEF was comprised of multipolar components, with monopoles indicating strong electro-diffusion, dendritic/axonal electrotonic current leakage outside SEF, or violations of the model assumptions. Our results also demonstrate the involvement of secondary cortical regions, in addition to SEF, particularly for the later Pe component. The dipolar component from the observed CSD paralleled the ERN dynamics, while the quadrupolar component paralleled the Pe. These results provide the most advanced explanation to date of the cellular mechanisms generating the ERN.
Asunto(s)
Electroencefalografía , Ritmo Teta , Animales , Células Piramidales , Lóbulo Frontal , Axones , Macaca , Potenciales EvocadosRESUMEN
Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.
Asunto(s)
Encéfalo , Potenciales Evocados , Animales , Humanos , Potenciales Evocados/fisiología , Encéfalo/fisiología , Macaca , Mapeo Encefálico , Electroencefalografía/métodosRESUMEN
Ca2+ spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+ spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+ and delayed-rectifier K+ conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (I h ), slow-inactivating K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking I h Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+ spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.SIGNIFICANCE STATEMENT A minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.
Asunto(s)
Biofisica , Modelos Neurológicos , Neocórtex/fisiología , Red Nerviosa/fisiología , Células Piramidales/fisiología , Algoritmos , Animales , Canales de Calcio Tipo L/fisiología , Señalización del Calcio/fisiología , Simulación por Computador , Canales de Potasio de Tipo Rectificador Tardío/fisiología , Dendritas/fisiología , Electroencefalografía , Potenciales Evocados/fisiología , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/fisiología , Macaca radiata , Masculino , Neocórtex/citología , Red Nerviosa/citología , Canales de Sodio/fisiologíaRESUMEN
The curtain of technical limitations impeding rat multichannel non-invasive electroencephalography (EEG) has risen. Given the importance of this preclinical model, development and validation of EEG source imaging (ESI) is essential. We investigate the validity of well-known human ESI methodologies in rats which individual tissue geometries have been approximated by those extracted from an MRI template, leading also to imprecision in electrode localizations. With the half and fifth sensitivity volumes we determine both the theoretical minimum electrode separation for non-redundant scalp EEG measurements and the electrode sensitivity resolution, which vary over the scalp because of the head geometry. According to our results, electrodes should be at least ~3 to 3.5 mm apart for an optimal configuration. The sensitivity resolution is generally worse for electrodes at the boundaries of the scalp measured region, though, by analogy with human montages, concentrates the sensitivity enough to localize sources. Cramér-Rao lower bounds of source localization errors indicate it is theoretically possible to achieve ESI accuracy at the level of anatomical structures, such as the stimulus-specific somatosensory areas, using the template. More validation for this approximation is provided through the comparison between the template and the individual lead field matrices, for several rats. Finally, using well-accepted inverse methods, we demonstrate that somatosensory ESI is not only expected but also allows exploring unknown phenomena related to global sensory integration. Inheriting the advantages and pitfalls of human ESI, rat ESI will boost the understanding of brain pathophysiological mechanisms and the evaluation of ESI methodologies, new pharmacological treatments and ESI-based biomarkers.
Asunto(s)
Mapeo Encefálico/métodos , Electroencefalografía/métodos , Animales , Encéfalo/fisiología , Encefalopatías , Electrodos , Humanos , Imagen por Resonancia Magnética , Masculino , Ratas , Cuero CabelludoRESUMEN
BACKGROUND: Apoptotic neuronal death is known as programmed cell death. Inhibition of this progression might contribute to a new treatment strategy. However, methods for in vivo detection of live apoptotic cells are in need to be developed and established. CONTEXT AND PURPOSE: The purpose of this study is to develop a new method for in vivo brain imaging for live apoptotic lesions using magnetic resonance imaging (MRI). We focused on the specific accumulation of our recently developed functional magnetic nanoparticles (FMNPs) into apoptotic cells using a rat cerebral ischemia model. Sulphorhodamine B, fluorescent dye was linked to valylalanylaspartic acid fluoromethyl ketone as a pan-caspase inhibitor to form SR-FLIVO. SR-FLIVO was bound with FMNPs to develop SR-FLIVO-FMNP probe. Ischemic rat brains were scanned by 7T MRI before and after intravenous injection of SR-FLIVO-FMNP and the distribution was evaluated by subtraction images of T2* colored mapping. SR-FLIVO, intracellular FMNPs, and T2* reduction area were histologically analyzed. The distribution of SR-FLIVO-FMNP was evaluated by subtracting the T2* signal images and was significantly correlated with the histological findings by TUNEL staining. RESULTS: Our experimental results revealed several findings where our newly developed probe SR-FLIVO-FMNP was intravenously administered into ischemic rats and FLIVO expression was tracked and found in apoptotic cells in rat brains after cerebral ischemia. A remarkable T2* reduction within the ischemic lesion was recorded using MRI based SR-FLIVO-FMNP probe as a contrasting agent due to the specific probe accumulation in apoptotic cells whereas, no observation of T2* reduction within the non-ischemic lesion due to no probe accumulation in non-apoptotic cells. Histological analysis based on the correlation between FLIVO and TUNEL staining showed that almost all FLIVO-positive cells were positive for TUNEL staining. These findings suggest the possibility for establishment of in vivo targeting delivery methods to live apoptotic cells based on conjugation of magnetic and fluorescent dual functional probes. CONCLUSION: A newly developed probe SR-FLIVO-FMNP might be considered as a useful probe for in vivo apoptotic detection, and FMNPs might be a strong platform for noninvasive imaging and targeting delivery.
Asunto(s)
Apoptosis/fisiología , Isquemia Encefálica/patología , Encéfalo/patología , Compuestos Férricos/administración & dosificación , Nanopartículas de Magnetita/administración & dosificación , Animales , Medios de Contraste/administración & dosificación , Imagen por Resonancia Magnética/métodos , Masculino , Ratas , Coloración y Etiquetado/métodosRESUMEN
The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas. In this minireview, we outline a tentative microcircuit model underlying cognitive control in the agranular frontal cortex of primates. The model incorporates the main GABAergic interneuron subclasses with specific laminar arrangements and target regions on pyramidal cells. We emphasize the role of layer 5 pyramidal cells in error and conflict detection. We offer several specific questions necessary for creating a specific intrinsic microcircuit model of the agranular frontal cortex.
Asunto(s)
Lóbulo Frontal , Macaca , Animales , Lóbulo Frontal/fisiología , Células Piramidales , Interneuronas , Haplorrinos , Primates , Cognición , Corteza CerebralRESUMEN
The simultaneous recordings of neuronal and hemodynamic signals have revealed a significant involvement of high frequency bands (e.g., gamma range, 25-70 Hz) in neurovascular coupling. However, the dependence on a physiological parameter is unknown. In this study, we performed simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings in 12 Wistar rats using a conventional forepaw stimulation paradigm and concurrently monitored the systemic physiological parameters of the partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, pH, mean arterial blood pressure, and heart rate through the rat femoral artery. The high frequency bands in the artifact-free EEG signals, especially those in the gamma range, demonstrated a maximum correlation with fMRI signals in the rat somatosensory cortex. A multiple linear regression analysis demonstrated that the correlation coefficient between the gamma power and fMRI signal depended on the actual values of the physiological parameters (R(2)=0.20, p<0.05), whereas the gamma power and fMRI signal by itself were independent. Among the parameters, the heart rate had a statistically significant slope (95% CI: 0.00027-0.0016, p<0.01) in a multiple linear regression model. These results indicate that neurovascular coupling is mainly driven by gamma oscillations, as expected, but coupling or potential decoupling is strongly influenced by systemic physiological parameters, which dynamically reflect the baseline vital status of the subject.
Asunto(s)
Electroencefalografía , Imagen por Resonancia Magnética , Corteza Somatosensorial/fisiología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
For about six decades, primary current sources of the electroencephalogram (EEG) have been assumed dipolar in nature. In this study, we used electrophysiological recordings from anesthetized Wistar rats undergoing repeated whisker deflections to revise the biophysical foundations of the EEG dipolar model. In a first experiment, we performed three-dimensional recordings of extracellular potentials from a large portion of the barrel field to estimate intracortical multipolar moments generated either by single spiking neurons (i.e., pyramidal cells, PC; spiny stellate cells, SS) or by populations of them while experiencing synchronized postsynaptic potentials. As expected, backpropagating spikes along PC dendrites caused dipolar field components larger in the direction perpendicular to the cortical surface (49.7 ± 22.0 nA·mm). In agreement with the fact that SS cells have "close-field" configurations, their dipolar moment at any direction was negligible. Surprisingly, monopolar field components were detectable both at the level of single units (i.e., -11.7 ± 3.4 nA for PC) and at the mesoscopic level of mixed neuronal populations receiving extended synaptic inputs within either a cortical column (-0.44 ± 0.20 µA) or a 2.5-m(3)-voxel volume (-3.32 ± 1.20 µA). To evaluate the relationship between the macroscopically defined EEG equivalent dipole and the mesoscopic intracortical multipolar moments, we performed concurrent recordings of high-resolution skull EEG and laminar local field potentials. From this second experiment, we estimated the time-varying EEG equivalent dipole for the entire barrel field using either a multiple dipole fitting or a distributed type of EEG inverse solution. We demonstrated that mesoscopic multipolar components are altogether absorbed by any equivalent dipole in both types of inverse solutions. We conclude that the primary current sources of the EEG in the neocortex of rodents are not precisely represented by a single equivalent dipole and that the existence of monopolar components must be also considered at the mesoscopic level.
Asunto(s)
Electroencefalografía/instrumentación , Electroencefalografía/métodos , Modelos Neurológicos , Neocórtex/fisiología , Animales , Masculino , Microelectrodos , Ratas , Ratas Wistar , Vibrisas/fisiologíaRESUMEN
Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is now widely accepted as a prevailing tool to study brain functions. For over a decade, EEG caps with high-dense arrays of electrodes for EEG-fMRI studies in humans have been commercially available. However, simultaneous EEG and fMRI recording in rodents has been limited to only a few electrodes due mainly to two technical reasons, i.e. a small available scalp area and the proximity of the electrodes to the brain tissue. In this paper, we introduce both a new EEG mini-cap and a protocol to obtain whole scalp EEG recordings simultaneously with 7 T fMRI signals in rodents. We provide methodological protocol to evaluate a number of problems emerging from the particulars of using rodents in simultaneous EEG and fMRI recording. The quality and reproducibility of both EEG and fMRI signals were demonstrated using a conventional forepaw stimulation paradigm in Wistar rats. Based on this quantitative analysis, we conclude that simultaneous EEG-fMRI recordings are achievable in rodents without significant signal loss. In light of the contemporary transgenic models and advanced drug administration protocols in rodents, the proposed methodology could be remarkable as a futurist experimental platform.
Asunto(s)
Encéfalo/anatomía & histología , Electroencefalografía/instrumentación , Imagen por Resonancia Magnética/instrumentación , Animales , Artefactos , Temperatura Corporal , Interpretación Estadística de Datos , Estimulación Eléctrica , Electrocardiografía , Campos Electromagnéticos , Electrónica , Potenciales Evocados/fisiología , Miembro Anterior/inervación , Miembro Anterior/fisiología , Procesamiento de Imagen Asistido por Computador , Miniaturización , Fantasmas de Imagen , Ratas , Ratas Wistar , TelemetríaRESUMEN
Alongside positive blood oxygenation level-dependent (BOLD) responses associated with interictal epileptic discharges, a variety of negative BOLD responses (NBRs) are typically found in epileptic patients. Previous studies suggest that, in general, up to four mechanisms might underlie the genesis of NBRs in the brain: (i) neuronal disruption of network activity, (ii) altered balance of neurometabolic/vascular couplings, (iii) arterial blood stealing, and (iv) enhanced cortical inhibition. Detecting and classifying these mechanisms from BOLD signals are pivotal for the improvement of the specificity of the electroencephalography-functional magnetic resonance imaging (EEG-fMRI) image modality to identify the seizure-onset zones in refractory local epilepsy. This requires models with physiological interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a Windkessel model with viscoelastic compliance/inductance in combination with dynamic models of both neuronal population activity and tissue/blood O2 to classify the hemodynamic response functions (HRFs) linked to the above mechanisms in the irritative zones of epileptic patients. First, we evaluated the most relevant imprints on the BOLD response caused by variations of key model parameters. Second, we demonstrated that a general linear model is enough to accurately represent the four different types of NBRs. Third, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying the BOLD signal from irritative zones. Cross-validation indicates that these four mechanisms can be classified from realistic fMRI BOLD signals. To demonstrate proof of concept, we applied our methodology to EEG-fMRI data from five epileptic patients undergoing neurosurgery, suggesting the presence of some of these mechanisms. We concluded that a proper identification and interpretation of NBR mechanisms in epilepsy can be performed by combining general linear models and biophysically inspired models.
RESUMEN
PURPOSE OF REVIEW: This review discusses our current understanding of the neurovascular coupling in the neocortex with particular emphasis on brain oscillations. RECENT FINDINGS: After two decades of developments in neuroimaging, we do not know thus far how blood perfusion is regulated regionally in our brain, a statement endorsed by the existing uncertainty about the strategies it employs for dynamic housekeeping and oxidative metabolism readjustment during evoked and ongoing processing. What is more, we have no clear idea why such a regulation is inhomogeneous for the entire neocortex, with special distinctions in those brain areas belonging to what has been named the resting default networks. In the light of recent findings about blood supplying mechanisms during brain oscillations, we have to regrettably admit that further experiments need yet to be carried out to have a better understanding of the neurovascular coupling in the cerebral cortex of mammals. SUMMARY: Understanding the neurovascular coupling, and hence the associated blood oxygenation level-dependent signal, will help us to design revolutionary therapies for several brain disorders as well as to establish new protocols for their diagnosis through neuroimaging. The brain oscillations provide us an ideal scenario for that end.
Asunto(s)
Relojes Biológicos/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Circulación Cerebrovascular/fisiología , Red Nerviosa/irrigación sanguínea , Red Nerviosa/fisiología , Animales , Encéfalo/metabolismo , Potenciales Evocados/fisiología , Humanos , Red Nerviosa/anatomía & histología , Fosforilación OxidativaRESUMEN
Wireless implantable neural interfaces can record high-resolution neuropotentials without constraining patient movement. Existing wireless systems often require intracranial wires to connect implanted electrodes to an external head stage or/and deploy an application-specific integrated circuit (ASIC), which is battery-powered or externally power-transferred, raising safety concerns such as infection, electronics failure, or heat-induced tissue damage. This work presents a biocompatible, flexible, implantable neural recorder capable of wireless acquisition of neuropotentials without wires, batteries, energy harvesting units, or active electronics. The recorder, fabricated on a thin polyimide substrate, features a small footprint of 9 mm × 8 mm × 0.3 mm and is composed of passive electronic components. The absence of active electronics on the device leads to near zero power consumption, inherently avoiding the catastrophic failure of active electronics. We performed both in vitro validation in a tissue-simulating phantom and in vivo validation in an epileptic rat. The fully passive wireless recorder was implanted under rat scalp to measure neuropotentials from its contact electrodes. The implanted wireless recorder demonstrated its capability to capture low voltage neuropotentials, including somatosensory evoked potentials (SSEPs), and interictal epileptiform discharges (IEDs). Wirelessly recorded SSEP and IED signals were directly compared to those from wired electrodes to demonstrate the efficacy of the wireless data. In addition, a convoluted neural network-based machine learning algorithm successfully achieved IED signal recognition accuracy as high as 100 and 91% in wired and wireless IED data, respectively. These results strongly support the fully passive wireless neural recorder's capability to measure neuropotentials as low as tens of microvolts. With further improvement, the recorder system presented in this work may find wide applications in future brain machine interface systems.
Asunto(s)
Electroencefalografía/métodos , Potenciales Evocados Somatosensoriales , Algoritmos , Animales , Materiales Biocompatibles/química , Encéfalo/metabolismo , Electrodos Implantados , Electroencefalografía/instrumentación , Aprendizaje Automático , Ratas Wistar , Tecnología Inalámbrica/instrumentaciónRESUMEN
α-Fe2O3 Magnetic nanoparticles (MNPs) have been synthesized, functionalized at silica that ends up with -NH2 group to form FMNPs. Conjugation of FMNPs with a fluorescently-labeled poly-caspase inhibitor valylalanylaspartic acid fluoromethyl ketone (SR-FLICA) which serves as a pan-caspase inhibitor was carried out to form finally a hybrid probe SR-FLICA-FMNPs. This probe could be used as a multimodal magneto-fluorescent platform for live apoptotic cells monitoring using MR and fluorescence imaging techniques. Characterization results of the as-synthesized MNPs and functionalized FMNPs by SEM, TEM, N2 isotherm, XRD and magnetic VSM showed that, a controlled morphological structure of MNPs could be synthesized with cubic-shaped, ferromagnetic, base-centered orthorhombic space group R3c and average size of 45.8⯱â¯3.2 and 50.3⯱â¯1.6â¯nm for MNPs and FMNPs, respectively. Phantom MRI experimental results of the examined MNPs and FMNPs confirmed the concentration dependency nature of T2 signal reduction. In addition, in vitro and in vivo sensing studies on our conjugated hybrid multifunctional probe SR-FLICA-FMNPs using 9â¯L gliosarcoma cells confirmed that; it could positively intact within the astrocytes and the nuclei of the apoptotic cells taking into account the starting material's cytotoxicity. Several histo-chemical protocols could be examined to confirm such behavior. Confocal and fluorescence microscopes' results of the histological stained apoptotic cells confirmed positive and specific expressions of our designed probe. MRI monitoring results of apoptotic rat models after focal brain transient cerebral ischemia showed a remarkable time-dependent reduction of T2* weighted signal up to 4â¯h indicating that our newly designed hybrid probe has long blood circulation and could be used as a future contrasting agent. Moreover, the distribution of our probe was evaluated by subtracting the T2* signal images before and after injection with SR-FLICA-FMNPs and was significantly correlated with the histological findings by staining via terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling. Moreover, clearance study confirmed that; our magneto-fluorescent hybrid probe could be cleared through liver Kupffer cells. Thus; the newly developed SR-FLICA-FMNPs could be considered as a future multifunctional probe for in vitro and in vivo apoptotic cells monitoring.
Asunto(s)
Apoptosis , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patología , Colorantes Fluorescentes/química , Nanopartículas de Magnetita/química , Animales , Línea Celular Tumoral , Supervivencia Celular , Rastreo Celular , Eritrocitos/metabolismo , Hemólisis , Humanos , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/ultraestructura , Ratas Sprague-Dawley , Relación Señal-Ruido , Propiedades de Superficie , Factores de TiempoRESUMEN
Understanding the link between neurobiology and cognition requires that neuroscience moves beyond mere structure-function correlations. An explicit systems perspective is needed in which putative mechanisms of how brain function is constrained by brain structure are mathematically formalized and made accessible for experimental investigation. Such a systems approach critically rests on a better understanding of brain connectivity in its various forms. Since 2002, frontier topics of connectivity and neural system analysis have been discussed in a multidisciplinary annual meeting, the Brain Connectivity Workshop (BCW), bringing together experimentalists and theorists from various fields. This article summarizes some of the main discussions at the two most recent workshops, 2006 at Sendai, Japan, and 2007 at Barcelona, Spain: (i) investigation of cortical micro- and macrocircuits, (ii) models of neural dynamics at multiple scales, (iii) analysis of "resting state" networks, and (iv) linking anatomical to functional connectivity. Finally, we outline some central challenges and research trajectories in computational systems neuroscience for the next years.
Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Modelos Neurológicos , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Neurociencias/tendencias , Animales , Biología Computacional/tendencias , Simulación por Computador , Humanos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiologíaRESUMEN
Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones, have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones-independent of them being epileptogenic-are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILß1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.
RESUMEN
Here we present a new methodology that investigates the intrinsic structural and hemodynamic characteristics of in vivo brain tissue, in a non-contact fashion, and can be easily incorporated in an intra-operative environment. Within this methodology, relative total diffuse reflectance spectra (RTD(λ)) were acquired from targets using a hybrid spectroscopy imaging system. A spectral interpretation algorithm was subsequently applied to RTD(λ) to retrieve optical properties related to the compositional and structural characteristics of each target. Estimation errors of the proposed methodology were computationally evaluated using a Monte Carlo simulation model for photon migration under various conditions. It was discovered that this new methodology could handle moderate noise and achieve very high accuracy, but only if the refractive index of the target is known. The accuracy of the technique was also validated using a series of tissue phantom studies, and consistent and accurate estimates of µs'(λ)/µa(λ) were obtained from all the phantoms tested. Finally, a small-scale animal study was conducted to demonstrate the clinical utility of the reported method, wherein a forepaw stimulation model was utilized to induce transient hemodynamic responses in somatosensory cortices. With this approach, significant stimulation-related changes (p < 0.001) in cortical hemodynamic and structural characteristics were successfully measured.
RESUMEN
The construction of three-dimensional images of the primary current density (PCD) produced by neuronal activity is a problem of great current interest in the neuroimaging community, though being initially formulated in the 1970s. There exist even now enthusiastic debates about the authenticity of most of the inverse solutions proposed in the literature, in which low resolution electrical tomography (LORETA) is a focus of attention. However, in our opinion, the capabilities and limitations of the electro and magneto encephalographic techniques to determine PCD configurations have not been extensively explored from a theoretical framework, even for simple volume conductor models of the head. In this paper, the electrophysiological inverse problem for the spherical head model is cast in terms of reproducing kernel Hilbert spaces (RKHS) formalism, which allows us to identify the null spaces of the implicated linear integral operators and also to define their representers. The PCD are described in terms of a continuous basis for the RKHS, which explicitly separates the harmonic and non-harmonic components. The RKHS concept permits us to bring LORETA into the scope of the general smoothing splines theory. A particular way of calculating the general smoothing splines is illustrated, avoiding a brute force discretization prematurely. The Bayes information criterion is used to handle dissimilarities in the signal/noise ratios and physical dimensions of the measurement modalities, which could affect the estimation of the amount of smoothness required for that class of inverse solution to be well specified. In order to validate the proposed method, we have estimated the 3D spherical smoothing splines from two data sets: electric potentials obtained from a skull phantom and magnetic fields recorded from subjects performing an experiment of human faces recognition.
Asunto(s)
Mapeo Encefálico , Imagenología Tridimensional , Modelos Biológicos , Algoritmos , Simulación por Computador , Electroencefalografía , Cabeza/anatomía & histología , Humanos , MagnetoencefalografíaRESUMEN
In order to elucidate the relationships between hierarchical structures within the neocortical neuropil and the information carried by an ensemble of neurons encompassing a single voxel, it is essential to predict through volume conductor modeling LFPs representing average extracellular potentials, which are expressed in terms of interstitial potentials of individual cells in networks of gap-junctionally connected astrocytes and synaptically connected neurons. These relationships have been provided and can then be used to investigate how the underlying neuronal population activity can be inferred from the measurement of the BOLD signal through electrovascular coupling mechanisms across the blood-brain barrier. The importance of both synaptic and extrasynaptic transmission as the basis of electrophysiological indices triggering vascular responses between dendritic and astrocytic networks, and sequential configurations of firing patterns in composite neural networks is emphasized. The purpose of this review is to show how fMRI data may be used to draw conclusions about the information transmitted by individual neurons in populations generating the BOLD signal.
Asunto(s)
Astrocitos/fisiología , Dendritas/fisiología , Imagen por Resonancia Magnética , Modelos Neurológicos , Red Nerviosa/fisiología , Neuronas/citología , Animales , Astrocitos/citología , Encéfalo/citología , Encéfalo/fisiología , Humanos , Aprendizaje/fisiología , Matemática , Redes Neurales de la Computación , Dinámicas no Lineales , Valor Predictivo de las PruebasRESUMEN
GOAL: We aim to evaluate the mechanisms underlying the neurovascular/metabolic coupling in the epileptogenic cortices of rats with chronic focal epilepsy. METHODS: We performed and analyzed intracranial recordings obtained from the seizure-onset zones during ictal periods on epileptic rats, and then, used these data to fit a metabolically coupled balloon model. Normal rats undergoing forepaw stimulation were used as control. RESULTS: We found a significant higher contribution from high local field potential frequency bands to the cerebral blood flow (CBF) responses in the epileptogenic cortices during ictal neuronal activities. The hemodynamic responses associated with ictal activities were distance-dependent with regard to the seizure focus, though varied in profiles from those obtained from acute seizure models. Parameters linking the CBF and relative concentration of deoxyhemoglobin to neuronal activity in the biophysical model were significantly different between epileptic and normal rats. CONCLUSION: We found that the coefficient associated with the strength of the functional hyperemic response was significantly larger in the epileptogenic cortices, and changes in hemoglobin concentration associated with ictal activity reflected the existence of a significantly higher baseline for oxygen metabolism in the epileptogenic cortices. SIGNIFICANCE: Introducing methods to estimate these physiological parameters would enhance our understanding of the neurovascular/metabolic coupling in epileptic brains and improve the localization accuracy on irritative zones and seizure-onset zones through neuroimaging techniques.