Sample records for localized brain activity
-
Real-time fMRI: a tool for local brain regulation.
Caria, Andrea; Sitaram, Ranganatha; Birbaumer, Niels
2012-10-01
Real-time fMRI permits simultaneous measurement and observation of brain activity during an ongoing task. One of the most challenging applications of real-time fMRI in neuroscientific and clinical research is the possibility of acquiring volitional control of localized brain activity using real-time fMRI-based neurofeedback protocols. Real-time fMRI allows the experimenter to noninvasively manipulate brain activity as an independent variable to observe the effects on behavior. Real-time fMRI neurofeedback studies demonstrated that learned control of the local brain activity leads to specific changes in behavior. Here, the authors describe the implementation and application of real-time fMRI with particular emphasis on the self-regulation of local brain activity and the investigation of brain-function relationships. Real-time fMRI represents a promising new approach to cognitive neuroscience that could complement traditional neuroimaging techniques by providing more causal insights into the functional role of circumscribed brain regions in behavior.
-
Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John
2015-01-01
A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119
-
Hierarchy of Information Processing in the Brain: A Novel 'Intrinsic Ignition' Framework.
Deco, Gustavo; Kringelbach, Morten L
2017-06-07
A general theory of brain function has to be able to explain local and non-local network computations over space and time. We propose a new framework to capture the key principles of how local activity influences global computation, i.e., describing the propagation of information and thus the broadness of communication driven by local activity. More specifically, we consider the diversity in space (nodes or brain regions) over time using the concept of intrinsic ignition, which are naturally occurring intrinsic perturbations reflecting the capability of a given brain area to propagate neuronal activity to other regions in a given brain state. Characterizing the profile of intrinsic ignition for a given brain state provides insight into the precise nature of hierarchical information processing. Combining this data-driven method with a causal whole-brain computational model can provide novel insights into the imbalance of brain states found in neuropsychiatric disorders. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.
2013-01-01
Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495
-
Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D
2013-10-01
To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.
-
Optogenetic mapping of brain circuitry
NASA Astrophysics Data System (ADS)
Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In
2012-10-01
Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.
-
NASA Astrophysics Data System (ADS)
Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong
2017-12-01
Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.
-
NASA Astrophysics Data System (ADS)
Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.
2017-06-01
Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.
-
Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.
2015-01-01
Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162
-
Rajabioun, Mehdi; Nasrabadi, Ali Motie; Shamsollahi, Mohammad Bagher
2017-09-01
Effective connectivity is one of the most important considerations in brain functional mapping via EEG. It demonstrates the effects of a particular active brain region on others. In this paper, a new method is proposed which is based on dual Kalman filter. In this method, firstly by using a brain active localization method (standardized low resolution brain electromagnetic tomography) and applying it to EEG signal, active regions are extracted, and appropriate time model (multivariate autoregressive model) is fitted to extracted brain active sources for evaluating the activity and time dependence between sources. Then, dual Kalman filter is used to estimate model parameters or effective connectivity between active regions. The advantage of this method is the estimation of different brain parts activity simultaneously with the calculation of effective connectivity between active regions. By combining dual Kalman filter with brain source localization methods, in addition to the connectivity estimation between parts, source activity is updated during the time. The proposed method performance has been evaluated firstly by applying it to simulated EEG signals with interacting connectivity simulation between active parts. Noisy simulated signals with different signal to noise ratios are used for evaluating method sensitivity to noise and comparing proposed method performance with other methods. Then the method is applied to real signals and the estimation error during a sweeping window is calculated. By comparing proposed method results in different simulation (simulated and real signals), proposed method gives acceptable results with least mean square error in noisy or real conditions.
-
Ling, Changying; Verbny, Yakov I.; Banks, Matthew I.; Sandor, Matyas; Fabry, Zsuzsanna
2012-01-01
The activation of Ag-specific T cells locally in the CNS could potentially contribute to the development of immune-mediated brain diseases. We addressed whether Ag-specific T cells could be stimulated in the CNS in the absence of peripheral lymphoid tissues by analyzing Ag-specific T cell responses in organotypic brain slice cultures. Organotypic brain slice cultures were established 1 h after intracerebral OVA Ag microinjection. We showed that when OVA-specific CD8+ T cells were added to Ag-containing brain slices, these cells became activated and migrated into the brain to the sites of their specific Ags. This activation of OVA-specific T cells was abrogated by the deletion of CD11c+ cells from the brain slices of the donor mice. These data suggest that brain-resident CD11c+ cells stimulate Ag-specific naive CD8+ T cells locally in the CNS and may contribute to immune responses in the brain. PMID:18523307
-
Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C
2016-06-22
In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain. Copyright © 2016 the authors 0270-6474/16/366704-14$15.00/0.
-
Instantaneous brain dynamics mapped to a continuous state space.
Billings, Jacob C W; Medda, Alessio; Shakil, Sadia; Shen, Xiaohong; Kashyap, Amrit; Chen, Shiyang; Abbas, Anzar; Zhang, Xiaodi; Nezafati, Maysam; Pan, Wen-Ju; Berman, Gordon J; Keilholz, Shella D
2017-11-15
Measures of whole-brain activity, from techniques such as functional Magnetic Resonance Imaging, provide a means to observe the brain's dynamical operations. However, interpretation of whole-brain dynamics has been stymied by the inherently high-dimensional structure of brain activity. The present research addresses this challenge through a series of scale transformations in the spectral, spatial, and relational domains. Instantaneous multispectral dynamics are first developed from input data via a wavelet filter bank. Voxel-level signals are then projected onto a representative set of spatially independent components. The correlation distance over the instantaneous wavelet-ICA state vectors is a graph that may be embedded onto a lower-dimensional space to assist the interpretation of state-space dynamics. Applying this procedure to a large sample of resting-state and task-active data (acquired through the Human Connectome Project), we segment the empirical state space into a continuum of stimulus-dependent brain states. Upon observing the local neighborhood of brain-states adopted subsequent to each stimulus, we may conclude that resting brain activity includes brain states that are, at times, similar to those adopted during tasks, but that are at other times distinct from task-active brain states. As task-active brain states often populate a local neighborhood, back-projection of segments of the dynamical state space onto the brain's surface reveals the patterns of brain activity that support many experimentally-defined states. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?
Lesku, John A; Vyssotski, Alexei L; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C
2011-08-22
The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.
-
Hu, Y; Wilson, G S
1997-10-01
A successfully developed enzyme-based lactate microsensor with rapid response time allows the direct and continuous in vivo measurement of lactic acid concentration with high temporal resolution in brain extracellular fluid. The fluctuations coupled to neuronal activity in extracellular lactate concentration were explored in the dentate gyrus of the hippocampus of the rat brain after electrical stimulation of the perforant pathway. Extracellular glucose and oxygen levels were also detected simultaneously by coimplantation of a fast-response glucose sensor and an oxygen electrode, to provide novel information of trafficking of energy substances in real time related to local neuronal activity. The results first give a comprehensive picture of complementary energy supply and use of lactate and glucose in the intact brain tissue. In response to acute neuronal activation, the brain tissue shifts immediately to significant energy supply by lactate. A local temporary fuel "reservoir" is established behind the blood-brain barrier, evidenced by increased extracellular lactate concentration. The pool can be depleted rapidly, up to 28% in 10-12 s, by massive, acute neuronal use after stimulation and can be replenished in approximately 20 s. Glutamate-stimulated astrocytic glycolysis and the increase of regional blood flow may regulate the lactate concentration of the pool in different time scales to maintain local energy homeostasis.
-
Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li
2013-01-01
Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378
-
Localization of synchronous cortical neural sources.
Zerouali, Younes; Herry, Christophe L; Jemel, Boutheina; Lina, Jean-Marc
2013-03-01
Neural synchronization is a key mechanism to a wide variety of brain functions, such as cognition, perception, or memory. High temporal resolution achieved by EEG recordings allows the study of the dynamical properties of synchronous patterns of activity at a very fine temporal scale but with very low spatial resolution. Spatial resolution can be improved by retrieving the neural sources of EEG signal, thus solving the so-called inverse problem. Although many methods have been proposed to solve the inverse problem and localize brain activity, few of them target the synchronous brain regions. In this paper, we propose a novel algorithm aimed at localizing specifically synchronous brain regions and reconstructing the time course of their activity. Using multivariate wavelet ridge analysis, we extract signals capturing the synchronous events buried in the EEG and then solve the inverse problem on these signals. Using simulated data, we compare results of source reconstruction accuracy achieved by our method to a standard source reconstruction approach. We show that the proposed method performs better across a wide range of noise levels and source configurations. In addition, we applied our method on real dataset and identified successfully cortical areas involved in the functional network underlying visual face perception. We conclude that the proposed approach allows an accurate localization of synchronous brain regions and a robust estimation of their activity.
-
Chowdhury, Rasheda Arman; Lina, Jean Marc; Kobayashi, Eliane; Grova, Christophe
2013-01-01
Localizing the generators of epileptic activity in the brain using Electro-EncephaloGraphy (EEG) or Magneto-EncephaloGraphy (MEG) signals is of particular interest during the pre-surgical investigation of epilepsy. Epileptic discharges can be detectable from background brain activity, provided they are associated with spatially extended generators. Using realistic simulations of epileptic activity, this study evaluates the ability of distributed source localization methods to accurately estimate the location of the generators and their sensitivity to the spatial extent of such generators when using MEG data. Source localization methods based on two types of realistic models have been investigated: (i) brain activity may be modeled using cortical parcels and (ii) brain activity is assumed to be locally smooth within each parcel. A Data Driven Parcellization (DDP) method was used to segment the cortical surface into non-overlapping parcels and diffusion-based spatial priors were used to model local spatial smoothness within parcels. These models were implemented within the Maximum Entropy on the Mean (MEM) and the Hierarchical Bayesian (HB) source localization frameworks. We proposed new methods in this context and compared them with other standard ones using Monte Carlo simulations of realistic MEG data involving sources of several spatial extents and depths. Detection accuracy of each method was quantified using Receiver Operating Characteristic (ROC) analysis and localization error metrics. Our results showed that methods implemented within the MEM framework were sensitive to all spatial extents of the sources ranging from 3 cm(2) to 30 cm(2), whatever were the number and size of the parcels defining the model. To reach a similar level of accuracy within the HB framework, a model using parcels larger than the size of the sources should be considered.
-
Chowdhury, Rasheda Arman; Lina, Jean Marc; Kobayashi, Eliane; Grova, Christophe
2013-01-01
Localizing the generators of epileptic activity in the brain using Electro-EncephaloGraphy (EEG) or Magneto-EncephaloGraphy (MEG) signals is of particular interest during the pre-surgical investigation of epilepsy. Epileptic discharges can be detectable from background brain activity, provided they are associated with spatially extended generators. Using realistic simulations of epileptic activity, this study evaluates the ability of distributed source localization methods to accurately estimate the location of the generators and their sensitivity to the spatial extent of such generators when using MEG data. Source localization methods based on two types of realistic models have been investigated: (i) brain activity may be modeled using cortical parcels and (ii) brain activity is assumed to be locally smooth within each parcel. A Data Driven Parcellization (DDP) method was used to segment the cortical surface into non-overlapping parcels and diffusion-based spatial priors were used to model local spatial smoothness within parcels. These models were implemented within the Maximum Entropy on the Mean (MEM) and the Hierarchical Bayesian (HB) source localization frameworks. We proposed new methods in this context and compared them with other standard ones using Monte Carlo simulations of realistic MEG data involving sources of several spatial extents and depths. Detection accuracy of each method was quantified using Receiver Operating Characteristic (ROC) analysis and localization error metrics. Our results showed that methods implemented within the MEM framework were sensitive to all spatial extents of the sources ranging from 3 cm2 to 30 cm2, whatever were the number and size of the parcels defining the model. To reach a similar level of accuracy within the HB framework, a model using parcels larger than the size of the sources should be considered. PMID:23418485
-
Neuropeptide Signaling Networks and Brain Circuit Plasticity.
McClard, Cynthia K; Arenkiel, Benjamin R
2018-01-01
The brain is a remarkable network of circuits dedicated to sensory integration, perception, and response. The computational power of the brain is estimated to dwarf that of most modern supercomputers, but perhaps its most fascinating capability is to structurally refine itself in response to experience. In the language of computers, the brain is loaded with programs that encode when and how to alter its own hardware. This programmed "plasticity" is a critical mechanism by which the brain shapes behavior to adapt to changing environments. The expansive array of molecular commands that help execute this programming is beginning to emerge. Notably, several neuropeptide transmitters, previously best characterized for their roles in hypothalamic endocrine regulation, have increasingly been recognized for mediating activity-dependent refinement of local brain circuits. Here, we discuss recent discoveries that reveal how local signaling by corticotropin-releasing hormone reshapes mouse olfactory bulb circuits in response to activity and further explore how other local neuropeptide networks may function toward similar ends.
-
Spatio-temporal Reconstruction of Neural Sources Using Indirect Dominant Mode Rejection.
Jafadideh, Alireza Talesh; Asl, Babak Mohammadzadeh
2018-04-27
Adaptive minimum variance based beamformers (MVB) have been successfully applied to magnetoencephalogram (MEG) and electroencephalogram (EEG) data to localize brain activities. However, the performance of these beamformers falls down in situations where correlated or interference sources exist. To overcome this problem, we propose indirect dominant mode rejection (iDMR) beamformer application in brain source localization. This method by modifying measurement covariance matrix makes MVB applicable in source localization in the presence of correlated and interference sources. Numerical results on both EEG and MEG data demonstrate that presented approach accurately reconstructs time courses of active sources and localizes those sources with high spatial resolution. In addition, the results of real AEF data show the good performance of iDMR in empirical situations. Hence, iDMR can be reliably used for brain source localization especially when there are correlated and interference sources.
-
Richards, Todd; Webb, Sara Jane; Murias, Michael; Merkle, Kristen; Kleinhans, Natalia M.; Johnson, L. Clark; Poliakov, Andrew; Aylward, Elizabeth; Dawson, Geraldine
2013-01-01
Brain activity patterns during face processing have been extensively explored with functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs). ERP source localization adds a spatial dimension to the ERP time series recordings, which allows for a more direct comparison and integration with fMRI findings. The goals for this study were (1) to compare the spatial descriptions of neuronal activity during face processing obtained with fMRI and ERP source localization using low-resolution electro-magnetic tomography (LORETA), and (2) to use the combined information from source localization and fMRI to explore how the temporal sequence of brain activity during face processing is summarized in fMRI activation maps. fMRI and high-density ERP data were acquired in separate sessions for 17 healthy adult males for a face and object processing task. LORETA statistical maps for the comparison of viewing faces and viewing houses were coregistered and compared to fMRI statistical maps for the same conditions. The spatial locations of face processing-sensitive activity measured by fMRI and LORETA were found to overlap in a number of areas including the bilateral fusiform gyri, the right superior, middle and inferior temporal gyri, and the bilateral precuneus. Both the fMRI and LORETA solutions additionally demon-strated activity in regions that did not overlap. fMRI and LORETA statistical maps of face processing-sensitive brain activity were found to converge spatially primarily at LORETA solution latencies that were within 18 ms of the N170 latency. The combination of data from these techniques suggested that electrical brain activity at the latency of the N170 is highly represented in fMRI statistical maps. PMID:19322649
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Winchell, H.S.; Horst, W.D.; Braun, L.
1980-10-01
The kinetics of N-isopropyl-p-(/sup 123/I)iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours.more » The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.« less
-
fMRI activation patterns in an analytic reasoning task: consistency with EEG source localization
NASA Astrophysics Data System (ADS)
Li, Bian; Vasanta, Kalyana C.; O'Boyle, Michael; Baker, Mary C.; Nutter, Brian; Mitra, Sunanda
2010-03-01
Functional magnetic resonance imaging (fMRI) is used to model brain activation patterns associated with various perceptual and cognitive processes as reflected by the hemodynamic (BOLD) response. While many sensory and motor tasks are associated with relatively simple activation patterns in localized regions, higher-order cognitive tasks may produce activity in many different brain areas involving complex neural circuitry. We applied a recently proposed probabilistic independent component analysis technique (PICA) to determine the true dimensionality of the fMRI data and used EEG localization to identify the common activated patterns (mapped as Brodmann areas) associated with a complex cognitive task like analytic reasoning. Our preliminary study suggests that a hybrid GLM/PICA analysis may reveal additional regions of activation (beyond simple GLM) that are consistent with electroencephalography (EEG) source localization patterns.
-
Noninvasive near-infrared topography of human brain activity using intensity modulation spectroscopy
NASA Astrophysics Data System (ADS)
Yamashita, Yuichi; Maki, Atsushi; Ito, Yoshitoshi; Watanabe, Eiju; Mayanagi, Yoshiaki; Koizumi, Hideaki
1996-04-01
We describe the functional topography of human brain activity due to motor stimulation by using near-infrared spectroscopy. Finger motion by each hand was used as the motor stimulation, and activity in the left fronto-central region of the brain was measured. A greater change in oxyhemoglobin concentration due to brain activity during the stimulation was obtained for the right hand than for the left hand. Localization of the activity was obtained by topographically mapping the measured changes for ten positions within the region.
-
Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.
Deniau, Jean-Michel; Degos, Bertrand; Bosch, Clémentine; Maurice, Nicolas
2010-10-01
Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
-
Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong
2016-11-01
The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.
-
THE LOCALIZATION OF ENZYME ACTIVITIES IN THE RAT BRAIN
Becker, Norwin H.; Goldfischer, Sidney; Shin, Woo-Yung; Novikoff, Alex B.
1960-01-01
Studies with rat brain illustrate the usefulness of formol-calcium-fixed tissue for studying both enzymatic "chemoarchitectonics" and intracellular organelles. Unembedded frozen sections and polyvinyl alcohol-embedded sections may be used to demonstrate the activities of DPNH-tetrazolium reductase localized in mitochondria and ergastoplasm, TPNH-tetrazolium reductase localized in mitochondria, ATPase (and/or apyrase or ADPase) in cell membranes, and acid phosphatase in lysosomes.1 Among the observations recorded are: (1) the presence of lysosomes in all cells of the brain; (2) the presence of numerous large lysosomes near the nuclei of capillary endothelial cells; (3) a polarized arrangement of large lysosomes in epithelial cells of the ependyma and choroid plexus; (4) the presence of ATPase activity in the cell membranes of some neurons; (5) the presence of either an apyrase or combination of ATPase and ADPase in the cell membranes of neuroglia and capillaries; (6) the presence of both DPNH- and TPNH-tetrazolium reductase activities in neuroglia; (7) the presence of DPNH- and TPNH-tetrazolium reductase activities in mitochondria and of DPNH-tetrazolium reductase activity in Nissl substance. The possible functional significance of these localizations is briefly discussed, as is their relation to "quantitative histochemistry" data available in the literature. PMID:13688468
-
The localization of enzyme activities in the rat brain.
BECKER, N H; GOLDFISCHER, S; SHIN, W Y; NOVIKOFF, A B
1960-12-01
Studies with rat brain illustrate the usefulness of formol-calcium-fixed tissue for studying both enzymatic "chemoarchitectonics" and intracellular organelles. Unembedded frozen sections and polyvinyl alcohol-embedded sections may be used to demonstrate the activities of DPNH-tetrazolium reductase localized in mitochondria and ergastoplasm, TPNH-tetrazolium reductase localized in mitochondria, ATPase (and/or apyrase or ADPase) in cell membranes, and acid phosphatase in lysosomes.(1) Among the observations recorded are: (1) the presence of lysosomes in all cells of the brain; (2) the presence of numerous large lysosomes near the nuclei of capillary endothelial cells; (3) a polarized arrangement of large lysosomes in epithelial cells of the ependyma and choroid plexus; (4) the presence of ATPase activity in the cell membranes of some neurons; (5) the presence of either an apyrase or combination of ATPase and ADPase in the cell membranes of neuroglia and capillaries; (6) the presence of both DPNH- and TPNH-tetrazolium reductase activities in neuroglia; (7) the presence of DPNH- and TPNH-tetrazolium reductase activities in mitochondria and of DPNH-tetrazolium reductase activity in Nissl substance. The possible functional significance of these localizations is briefly discussed, as is their relation to "quantitative histochemistry" data available in the literature.
-
Brain science: from the very small to the very large.
Kreiman, Gabriel
2007-09-04
We still lack a clear understanding of how brain imaging signals relate to neuronal activity. Recent work shows that the simultaneous activity of neuronal ensembles strongly correlates with local field potentials and imaging measurements.
-
Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.
Churilla, Thomas M; Weiss, Stephanie E
2018-05-07
To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.
-
Brain MRI Tumor Detection using Active Contour Model and Local Image Fitting Energy
NASA Astrophysics Data System (ADS)
Nabizadeh, Nooshin; John, Nigel
2014-03-01
Automatic abnormality detection in Magnetic Resonance Imaging (MRI) is an important issue in many diagnostic and therapeutic applications. Here an automatic brain tumor detection method is introduced that uses T1-weighted images and K. Zhang et. al.'s active contour model driven by local image fitting (LIF) energy. Local image fitting energy obtains the local image information, which enables the algorithm to segment images with intensity inhomogeneities. Advantage of this method is that the LIF energy functional has less computational complexity than the local binary fitting (LBF) energy functional; moreover, it maintains the sub-pixel accuracy and boundary regularization properties. In Zhang's algorithm, a new level set method based on Gaussian filtering is used to implement the variational formulation, which is not only vigorous to prevent the energy functional from being trapped into local minimum, but also effective in keeping the level set function regular. Experiments show that the proposed method achieves high accuracy brain tumor segmentation results.
-
A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Choi, Joungil, E-mail: jochoi@som.umaryland.edu; Veterans Affairs Medical Center, Baltimore, MD 21201; Batchu, Vera Venkatanaresh Kumar
2013-06-14
Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α isoform localizes to the mitochondrial inner membrane and matrix in brain as determined by protease protection and carbonate extraction assays, as well asmore » by immunoelectron microscopy. Immunoelectron microscopy and import experiments in vitro revealed that 35 kDa PGC-1α colocalizes and interacts with the voltage-dependent anion channel (VDAC), and that its import depends on VDAC. Valinomycin treatment which depolarizes the membrane potential, abolished mitochondrial localization of the 35 kDa PGC-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.« less
-
De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G
2015-03-01
Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes. © 2015 John Wiley & Sons Ltd.
-
Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H
2004-07-01
This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.
-
Willemse, Ronald B.; Hillebrand, Arjan; Ronner, Hanneke E.; Peter Vandertop, W.; Stam, Cornelis J.
2015-01-01
Objectives The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. Methods Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. Results The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3–50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). Conclusions MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits. PMID:26693401
-
Vairavan, Srinivasan; Eswaran, Hari; Preissl, Hubert; Wilson, James D; Haddad, Naim; Lowery, Curtis L; Govindan, Rathinaswamy B
2010-01-01
The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.
-
Pre-seizure state identified by diffuse optical tomography
Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei
2014-01-01
In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. PMID:24445927
-
2013-01-01
Background There is an accumulating body of evidence indicating that neuronal functional specificity to basic sensory stimulation is mutable and subject to experience. Although fMRI experiments have investigated changes in brain activity after relative to before perceptual learning, brain activity during perceptual learning has not been explored. This work investigated brain activity related to auditory frequency discrimination learning using a variational Bayesian approach for source localization, during simultaneous EEG and fMRI recording. We investigated whether the practice effects are determined solely by activity in stimulus-driven mechanisms or whether high-level attentional mechanisms, which are linked to the perceptual task, control the learning process. Results The results of fMRI analyses revealed significant attention and learning related activity in left and right superior temporal gyrus STG as well as the left inferior frontal gyrus IFG. Current source localization of simultaneously recorded EEG data was estimated using a variational Bayesian method. Analysis of current localized to the left inferior frontal gyrus and the right superior temporal gyrus revealed gamma band activity correlated with behavioral performance. Conclusions Rapid improvement in task performance is accompanied by plastic changes in the sensory cortex as well as superior areas gated by selective attention. Together the fMRI and EEG results suggest that gamma band activity in the right STG and left IFG plays an important role during perceptual learning. PMID:23316957
-
NASA Astrophysics Data System (ADS)
Almurshedi, Ahmed; Ismail, Abd Khamim
2015-04-01
EEG source localization was studied in order to determine the location of the brain sources that are responsible for the measured potentials at the scalp electrodes using EEGLAB with Independent Component Analysis (ICA) algorithm. Neuron source locations are responsible in generating current dipoles in different states of brain through the measured potentials. The current dipole sources localization are measured by fitting an equivalent current dipole model using a non-linear optimization technique with the implementation of standardized boundary element head model. To fit dipole models to ICA components in an EEGLAB dataset, ICA decomposition is performed and appropriate components to be fitted are selected. The topographical scalp distributions of delta, theta, alpha, and beta power spectrum and cross coherence of EEG signals are observed. In close eyes condition it shows that during resting and action states of brain, alpha band was activated from occipital (O1, O2) and partial (P3, P4) area. Therefore, parieto-occipital area of brain are active in both resting and action state of brain. However cross coherence tells that there is more coherence between right and left hemisphere in action state of brain than that in the resting state. The preliminary result indicates that these potentials arise from the same generators in the brain.
-
Regularized two-step brain activity reconstruction from spatiotemporal EEG data
NASA Astrophysics Data System (ADS)
Alecu, Teodor I.; Voloshynovskiy, Sviatoslav; Pun, Thierry
2004-10-01
We are aiming at using EEG source localization in the framework of a Brain Computer Interface project. We propose here a new reconstruction procedure, targeting source (or equivalently mental task) differentiation. EEG data can be thought of as a collection of time continuous streams from sparse locations. The measured electric potential on one electrode is the result of the superposition of synchronized synaptic activity from sources in all the brain volume. Consequently, the EEG inverse problem is a highly underdetermined (and ill-posed) problem. Moreover, each source contribution is linear with respect to its amplitude but non-linear with respect to its localization and orientation. In order to overcome these drawbacks we propose a novel two-step inversion procedure. The solution is based on a double scale division of the solution space. The first step uses a coarse discretization and has the sole purpose of globally identifying the active regions, via a sparse approximation algorithm. The second step is applied only on the retained regions and makes use of a fine discretization of the space, aiming at detailing the brain activity. The local configuration of sources is recovered using an iterative stochastic estimator with adaptive joint minimum energy and directional consistency constraints.
-
Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.
Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian
2017-07-13
Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain
2016-01-01
Abstract What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain. PMID:27517084
-
Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain.
Cohen, Dror; Zalucki, Oressia H; van Swinderen, Bruno; Tsuchiya, Naotsugu
2016-01-01
What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli ('frequency tags') allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain.
-
Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra
2014-12-01
Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.
-
NeuroGrid: recording action potentials from the surface of the brain.
Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György
2015-02-01
Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.
-
Multi-frequency localization of aberrant brain activity in autism spectrum disorder.
Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S
2016-01-01
The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
-
Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M
2016-05-01
Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
-
Simultaneous EEG and MEG source reconstruction in sparse electromagnetic source imaging.
Ding, Lei; Yuan, Han
2013-04-01
Electroencephalography (EEG) and magnetoencephalography (MEG) have different sensitivities to differently configured brain activations, making them complimentary in providing independent information for better detection and inverse reconstruction of brain sources. In the present study, we developed an integrative approach, which integrates a novel sparse electromagnetic source imaging method, i.e., variation-based cortical current density (VB-SCCD), together with the combined use of EEG and MEG data in reconstructing complex brain activity. To perform simultaneous analysis of multimodal data, we proposed to normalize EEG and MEG signals according to their individual noise levels to create unit-free measures. Our Monte Carlo simulations demonstrated that this integrative approach is capable of reconstructing complex cortical brain activations (up to 10 simultaneously activated and randomly located sources). Results from experimental data showed that complex brain activations evoked in a face recognition task were successfully reconstructed using the integrative approach, which were consistent with other research findings and validated by independent data from functional magnetic resonance imaging using the same stimulus protocol. Reconstructed cortical brain activations from both simulations and experimental data provided precise source localizations as well as accurate spatial extents of localized sources. In comparison with studies using EEG or MEG alone, the performance of cortical source reconstructions using combined EEG and MEG was significantly improved. We demonstrated that this new sparse ESI methodology with integrated analysis of EEG and MEG data could accurately probe spatiotemporal processes of complex human brain activations. This is promising for noninvasively studying large-scale brain networks of high clinical and scientific significance. Copyright © 2011 Wiley Periodicals, Inc.
-
Cicmil, Nela; Bridge, Holly; Parker, Andrew J.; Woolrich, Mark W.; Krug, Kristine
2014-01-01
Magnetoencephalography (MEG) allows the physiological recording of human brain activity at high temporal resolution. However, spatial localization of the source of the MEG signal is an ill-posed problem as the signal alone cannot constrain a unique solution and additional prior assumptions must be enforced. An adequate source reconstruction method for investigating the human visual system should place the sources of early visual activity in known locations in the occipital cortex. We localized sources of retinotopic MEG signals from the human brain with contrasting reconstruction approaches (minimum norm, multiple sparse priors, and beamformer) and compared these to the visual retinotopic map obtained with fMRI in the same individuals. When reconstructing brain responses to visual stimuli that differed by angular position, we found reliable localization to the appropriate retinotopic visual field quadrant by a minimum norm approach and by beamforming. Retinotopic map eccentricity in accordance with the fMRI map could not consistently be localized using an annular stimulus with any reconstruction method, but confining eccentricity stimuli to one visual field quadrant resulted in significant improvement with the minimum norm. These results inform the application of source analysis approaches for future MEG studies of the visual system, and indicate some current limits on localization accuracy of MEG signals. PMID:24904268
-
Labandeira-Garcia, Jose L.; Rodríguez-Perez, Ana I.; Garrido-Gil, Pablo; Rodriguez-Pallares, Jannette; Lanciego, Jose L.; Guerra, Maria J.
2017-01-01
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS) has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1 receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR) signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1 (IGF-1), tumor necrosis factor α (TNF)-α, iron, peroxisome proliferator-activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming has recently been involved in the regulation of the neuroinflammatory response. Interestingly, we have recently observed a mitochondrial RAS, which is altered in aged brains. In conclusion, dysregulation of brain RAS plays a major role in aging-related changes and neurodegeneration by exacerbation of oxidative stress (OS) and neuroinflammation, which may be attenuated by pharmacological manipulation of RAS components. PMID:28515690
-
Völker, Martin; Fiederer, Lukas D J; Berberich, Sofie; Hammer, Jiří; Behncke, Joos; Kršek, Pavel; Tomášek, Martin; Marusič, Petr; Reinacher, Peter C; Coenen, Volker A; Helias, Moritz; Schulze-Bonhage, Andreas; Burgard, Wolfram; Ball, Tonio
2018-06-01
Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
-
Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas
2012-08-01
In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.
-
Cell and brain tissue imaging of the flavonoid fisetin using label-free two-photon microscopy.
Krasieva, Tatiana B; Ehren, Jennifer; O'Sullivan, Thomas; Tromberg, Bruce J; Maher, Pamela
2015-10-01
Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglia and astrocytes and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. However, key questions about its targets and brain penetration remain. In this study, we used label-free two-photon microscopy of intrinsic fisetin fluorescence to examine the localization of fisetin in living nerve cells and the brains of living mice. In cells, fisetin but not structurally related flavonols with different numbers of hydroxyl groups, localized to the nucleoli suggesting that key targets of fisetin may reside in this organelle. In the mouse brain, following intraperitoneal injection and oral administration, fisetin rapidly distributed to the blood vessels of the brain followed by a slower dispersion into the brain parenchyma. Thus, these results provide further support for the effects of fisetin on brain function. In addition, they suggest that label-free two-photon microscopy may prove useful for studying the intracellular and tissue distribution of other intrinsically-fluorescent flavonoids. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Cell and Brain Tissue Imaging of the Flavonoid Fisetin Using Label-Free Two-Photon Microscopy
Krasieva, Tatiana B.; Ehren, Jennifer; O’Sullivan, Thomas; Tromberg, Bruce J.; Maher, Pamela
2015-01-01
Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglia and astrocytes and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their byproducts. However, key questions about its targets and brain penetration remain. In this study, we used label-free two-photon microscopy of intrinsic fisetin fluorescence to examine the localization of fisetin in living nerve cells and the brains of living mice. In cells, fisetin but not structurally related flavonols with different numbers of hydroxyl groups, localized to the nucleoli suggesting that key targets of fisetin may reside in this organelle. In the mouse brain, following intraperitoneal injection and oral administration, fisetin rapidly distributed to the blood vessels of the brain followed by a slower dispersion into the brain parenchyma. Thus, these results provide further support for the effects of fisetin on brain function. In addition, they suggest that label-free two-photon microscopy may prove useful for studying the intracellular and tissue distribution of other intrinsically-fluorescent flavonoids. PMID:26271433
-
On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review
Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo
2013-01-01
Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579
-
Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang
2018-01-01
Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
-
Neubauer, Florian B; Sederberg, Audrey; MacLean, Jason N
2014-01-01
During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.
-
Neubauer, Florian B.; Sederberg, Audrey; MacLean, Jason N.
2014-01-01
During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges. PMID:25232306
-
Cao, Song; Li, Ying; Deng, Wenwen; Qin, Bangyong; Zhang, Yi; Xie, Peng; Yuan, Jie; Yu, Buwei; Yu, Tian
2017-07-01
Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known. To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients. Observational study. University hospital. Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains. Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease. (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences. HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition. Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).
-
Social reinforcement can regulate localized brain activity.
Mathiak, Krystyna A; Koush, Yury; Dyck, Miriam; Gaber, Tilman J; Alawi, Eliza; Zepf, Florian D; Zvyagintsev, Mikhail; Mathiak, Klaus
2010-11-01
Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided a positive feedback (smiling) when activity in the anterior cingulate cortex (ACC) increased and gradually returned to a neutral expression when the activity dropped. One female volunteer without previous experience in fMRI underwent training based on a social reinforcer. Directly before and after the neurofeedback runs, neural responses to a cognitive interference task (Simon task) were recorded. We observed a significant increase in activity within ACC during the neurofeedback blocks, correspondent with the a-priori defined anatomical region of interest. In the course of the neurofeedback training, the subject learned to regulate ACC activity and could maintain the control even without direct feedback. Moreover, ACC was activated significantly stronger during Simon task after the neurofeedback training when compared to before. Localized brain activity can be controlled by social reward. The increased ACC activity transferred to a cognitive task with the potential to reduce cognitive interference. Systematic studies are required to explore long-term effects on social behavior and clinical applications.
-
Tsolaki, Anthoula C; Kosmidou, Vasiliki E; Kompatsiaris, Ioannis Yiannis; Papadaniil, Chrysa; Hadjileontiadis, Leontios; Tsolaki, Magda
2017-01-06
Identifying the brain sources of neural activation during processing of emotional information remains a very challenging task. In this work, we investigated the response to different emotional stimuli and the effect of age on the neuronal activation. Two negative emotion conditions, i.e., 'anger' and 'fear' faces were presented to 22 adult female participants (11 young and 11 elderly) while acquiring high-density electroencephalogram (EEG) data of 256 channels. Brain source localization was utilized to study the modulations in the early N170 event-related-potential component. The results revealed alterations in the amplitude of N170 and the localization of areas with maximum neural activation. Furthermore, age-induced differences are shown in the topographic maps and the neural activation for both emotional stimuli. Overall, aging appeared to affect the limbic area and its implication to emotional processing. These findings can serve as a step toward the understanding of the way the brain functions and evolves with age which is a significant element in the design of assistive environments. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
-
Tagliazucchi, Enzo; Sanjuán, Ana
2017-01-01
Abstract A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states. PMID:28966977
-
Deco, Gustavo; Tagliazucchi, Enzo; Laufs, Helmut; Sanjuán, Ana; Kringelbach, Morten L
2017-01-01
A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.
-
Local vs. volume conductance activity of field potentials in the human subthalamic nucleus
Marmor, Odeya; Valsky, Dan; Joshua, Mati; Bick, Atira S; Arkadir, David; Tamir, Idit; Bergman, Hagai; Israel, Zvi
2017-01-01
Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms. PMID:28202569
-
Mapping Prefrontal Cortex Functions in Human Infancy
ERIC Educational Resources Information Center
Grossmann, Tobias
2013-01-01
It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…
-
Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.
Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc
2016-06-16
Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.
-
Mapping of brain activity by automated volume analysis of immediate early genes
Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc
2016-01-01
Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021
-
Gilson, Matthieu; Deco, Gustavo; Friston, Karl J; Hagmann, Patric; Mantini, Dante; Betti, Viviana; Romani, Gian Luca; Corbetta, Maurizio
2017-10-09
Our behavior entails a flexible and context-sensitive interplay between brain areas to integrate information according to goal-directed requirements. However, the neural mechanisms governing the entrainment of functionally specialized brain areas remain poorly understood. In particular, the question arises whether observed changes in the regional activity for different cognitive conditions are explained by modifications of the inputs to the brain or its connectivity? We observe that transitions of fMRI activity between areas convey information about the tasks performed by 19 subjects, watching a movie versus a black screen (rest). We use a model-based framework that explains this spatiotemporal functional connectivity pattern by the local variability for 66 cortical regions and the network effective connectivity between them. We find that, among the estimated model parameters, movie viewing affects to a larger extent the local activity, which we interpret as extrinsic changes related to the increased stimulus load. However, detailed changes in the effective connectivity preserve a balance in the propagating activity and select specific pathways such that high-level brain regions integrate visual and auditory information, in particular boosting the communication between the two brain hemispheres. These findings speak to a dynamic coordination underlying the functional integration in the brain. Copyright © 2017. Published by Elsevier Inc.
-
Chiu, Hou-Chang
2009-06-01
The brain is the window of the artistic mind. Brain activities lead to the understanding of the outside world by perception and cognition, and the enjoyment of the artistic wonders. This article will demonstrate how different brain areas are responsible for the creative abilities of painting, music, and literature. Due to the advancement in neuroscientic techniques such as functional MRI, brain electric activity mapping, etc, we explore and understand the brain areas that are responsible for cognition and artistic creation. We also understand the functional localization of mental activities from neurological patients with lesions in different brain areas. On the other hand, the artists had produced great works in a way similar to finding the related brain areas in the stimulation experiments. Therefore, many neuroscientists have praised that artists are outstanding neurologists.
-
Ohmatsu, Satoko; Nakano, Hideki; Tominaga, Takanori; Terakawa, Yuzo; Murata, Takaho; Morioka, Shu
2014-08-15
Pedaling exercise (PE) of moderate intensity has been shown to ease anxiety and discomfort; however, little is known of the changes that occur in brain activities and in the serotonergic (5-HT) system after PE. Therefore, this study was conducted for the following reasons: (1) to localize the changes in the brain activities induced by PE using a distributed source localization algorithm, (2) to examine the changes in frontal asymmetry, as used in the Davidson model, with electroencephalography (EEG) activity, and (3) to examine the effect of PE on the 5-HT system. A 32-channel EEG was used to record before and after PE. Profile of Mood States tests indicated that there was a significant decrease in tension-anxiety and a significant increase in vigor after PE. A standardized low-resolution brain electromagnetic tomography analysis showed a significant decrease in brain activities after PE in the alpha-2 band (10-12.5 Hz) in the anterior cingulate cortex (ACC). Moreover, a significant increase in frontal EEG asymmetry was observed after PE in the alpha-1 band (7.5-10 Hz). Urine 5-HT levels significantly increased after PE. Urine 5-HT levels positively correlated with the degree of frontal EEG asymmetry in the alpha-1 band and negatively correlated with brain activity in ACC. Our results suggested that PE activates the 5-HT system and consequently induces increases in frontal EEG asymmetry in the alpha-1 band and reductions of brain activity in the alpha-2 band in the ACC region. Copyright © 2014 Elsevier B.V. All rights reserved.
-
From blood oxygenation level dependent (BOLD) signals to brain temperature maps.
Sotero, Roberto C; Iturria-Medina, Yasser
2011-11-01
A theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to brain temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO₂) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model, we obtain a transcendental equation relating CBF and CMRO₂ changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bioheat equation describing the rate of temperature changes in the brain, we obtain a nonautonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. Temperature maps obtained from a real BOLD dataset registered in an attention to visual motion experiment were calculated, obtaining temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The statistical analysis revealed that significant temperature activations have a similar distribution pattern than BOLD activations. An interesting difference was the activation of the precuneus in temperature maps, a region involved in visuospatial processing, an effect that was not observed on BOLD maps. Furthermore, temperature maps were more localized to gray matter regions than the original BOLD maps, showing less activated voxels in white matter and cerebrospinal fluid.
-
Rojas-Líbano, Daniel; Wimmer Del Solar, Jonathan; Aguilar-Rivera, Marcelo; Montefusco-Siegmund, Rodrigo; Maldonado, Pedro Esteban
2018-05-16
An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this article, we asked if there are modulations of local cortical processing which are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through EMG and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal's OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions.
-
Regional Slow Waves and Spindles in Human Sleep
Nir, Yuval; Staba, Richard J.; Andrillon, Thomas; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Fried, Itzhak; Tononi, Giulio
2011-01-01
SUMMARY The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions—are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions. PMID:21482364
-
Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.
Maurya, Shashank Kumar; Mishra, Rajnikant
2017-07-01
The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Cepeda-Negrete, Jonathan; Ibarra-Manzano, Mario Alberto; Chalopin, Claire
2017-12-01
Brain tumor segmentation is a routine process in a clinical setting and provides useful information for diagnosis and treatment planning. Manual segmentation, performed by physicians or radiologists, is a time-consuming task due to the large quantity of medical data generated presently. Hence, automatic segmentation methods are needed, and several approaches have been introduced in recent years including the Localized Region-based Active Contour Model (LRACM). There are many popular LRACM, but each of them presents strong and weak points. In this paper, the automatic selection of LRACM based on image content and its application on brain tumor segmentation is presented. Thereby, a framework to select one of three LRACM, i.e., Local Gaussian Distribution Fitting (LGDF), localized Chan-Vese (C-V) and Localized Active Contour Model with Background Intensity Compensation (LACM-BIC), is proposed. Twelve visual features are extracted to properly select the method that may process a given input image. The system is based on a supervised approach. Applied specifically to Magnetic Resonance Imaging (MRI) images, the experiments showed that the proposed system is able to correctly select the suitable LRACM to handle a specific image. Consequently, the selection framework achieves better accuracy performance than the three LRACM separately. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Direct imaging of neural currents using ultra-low field magnetic resonance techniques
Volegov, Petr L [Los Alamos, NM; Matlashov, Andrei N [Los Alamos, NM; Mosher, John C [Los Alamos, NM; Espy, Michelle A [Los Alamos, NM; Kraus, Jr., Robert H.
2009-08-11
Using resonant interactions to directly and tomographically image neural activity in the human brain using magnetic resonance imaging (MRI) techniques at ultra-low field (ULF), the present inventors have established an approach that is sensitive to magnetic field distributions local to the spin population in cortex at the Larmor frequency of the measurement field. Because the Larmor frequency can be readily manipulated (through varying B.sub.m), one can also envision using ULF-DNI to image the frequency distribution of the local fields in cortex. Such information, taken together with simultaneous acquisition of MEG and ULF-NMR signals, enables non-invasive exploration of the correlation between local fields induced by neural activity in cortex and more `distant` measures of brain activity such as MEG and EEG.
-
Inferring brain-computational mechanisms with models of activity measurements
Diedrichsen, Jörn
2016-01-01
High-resolution functional imaging is providing increasingly rich measurements of brain activity in animals and humans. A major challenge is to leverage such data to gain insight into the brain's computational mechanisms. The first step is to define candidate brain-computational models (BCMs) that can perform the behavioural task in question. We would then like to infer which of the candidate BCMs best accounts for measured brain-activity data. Here we describe a method that complements each BCM by a measurement model (MM), which simulates the way the brain-activity measurements reflect neuronal activity (e.g. local averaging in functional magnetic resonance imaging (fMRI) voxels or sparse sampling in array recordings). The resulting generative model (BCM-MM) produces simulated measurements. To avoid having to fit the MM to predict each individual measurement channel of the brain-activity data, we compare the measured and predicted data at the level of summary statistics. We describe a novel particular implementation of this approach, called probabilistic representational similarity analysis (pRSA) with MMs, which uses representational dissimilarity matrices (RDMs) as the summary statistics. We validate this method by simulations of fMRI measurements (locally averaging voxels) based on a deep convolutional neural network for visual object recognition. Results indicate that the way the measurements sample the activity patterns strongly affects the apparent representational dissimilarities. However, modelling of the measurement process can account for these effects, and different BCMs remain distinguishable even under substantial noise. The pRSA method enables us to perform Bayesian inference on the set of BCMs and to recognize the data-generating model in each case. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574316
-
Sakurai, Yoshio
2014-01-01
This perspective emphasizes that the brain-machine interface (BMI) research has the potential to clarify major mysteries of the brain and that such clarification of the mysteries by neuroscience is needed to develop BMIs. I enumerate five principal mysteries. The first is "how is information encoded in the brain?" This is the fundamental question for understanding what our minds are and is related to the verification of Hebb's cell assembly theory. The second is "how is information distributed in the brain?" This is also a reconsideration of the functional localization of the brain. The third is "what is the function of the ongoing activity of the brain?" This is the problem of how the brain is active during no-task periods and what meaning such spontaneous activity has. The fourth is "how does the bodily behavior affect the brain function?" This is the problem of brain-body interaction, and obtaining a new "body" by a BMI leads to a possibility of changes in the owner's brain. The last is "to what extent can the brain induce plasticity?" Most BMIs require changes in the brain's neuronal activity to realize higher performance, and the neuronal operant conditioning inherent in the BMIs further enhances changes in the activity.
-
Rapid control of male typical behaviors by brain-derived estrogens
Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques
2012-01-01
Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088
-
Henkin, R I; Levy, L M
2001-01-01
Our goal was to use functional MRI (fMRI) of brain to reveal activation in each cerebral hemisphere in response to imagination and smell of odors. FMRI brain scans were obtained in 24 normal subjects using multislice fast low angle shot (FLASH) MRI in response to imagination of banana and peppermint odors and in response to smell of corresponding odors of amyl acetate and menthone, respectively, and of pyridine. Three coronal sections selected from anterior to posterior brain regions were used. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging (EPI) both before and after theophylline treatment that returned smell function to or toward normal in each patient and in two patients with birhinal phantosmia (persistent foul odor) and global phantogeusia (persistent foul taste) with FLASH and EPI fMRI before and after treatment with neuroleptic drugs that inhibited their phantosmia and phantogeusia. Activation images were derived using correlation analysis. Ratios of hemispheric areas of brain activation to total hemispheric brain areas were calculated for FLASH fMRI, and numerical counts of pixel clusters in each hemisphere were made for EPI studies. Total pixel cluster counts in localized regions of each hemispheric section were also obtained. In normal subjects, activation generally occurred in left (L) > right (R) brain hemisphere in response to banana and peppermint odor imagination and to smell of corresponding odors of amyl acetate and menthone. Whereas there were no overall hemispheric differences for pyridine odor, activation in men was R > L hemisphere. Although absolute activation in both L and R hemispheres in response to banana odor imagination and amyl acetate smell was men > women, the ratio of L to R activation was women > men. In hyposmic patients studied by FLASH fMRI, activation to banana odor imagination and amyl acetate smell was L > R hemisphere both before and after theophylline treatment. In the hyposmic patient studied with EPI before theophylline treatment, activation to banana and peppermint odor imagination and to amyl acetate, menthone, and pyridine smell was R > L hemisphere; after theophylline treatment restored normal smell function, activation shifted completely with banana and peppermint odor imagination and amyl acetate and menthone smell to L > R hemisphere, consistent with responses in normal subjects. However, this shift also occurred for pyridine smell, which is opposite to responses in normal control subjects. In patients with phantosmia and phantogeusia, activation to phantosmia and phantogeusia before treatment was R > L hemisphere; after treatment inhibited phantosmia and phantogeusia, activation shifted with a slight L > R hemispheric lateralization. Localization of all lateralized responses indicated that anterior frontal and temporal cortices were brain regions most involved with imagination and smell of odors and with phantosmia and phantogeusia presence. Imagination and smell of odors perceived as pleasant generally activated the dominant or L > R brain hemisphere. Smell of odors perceived as unpleasant and unpleasant phantosmia and phantogeusia generally activated the contralateral or R > L brain hemisphere. With remission of phantosmia and phantogeusia, hemispheric activation was not only inhibited, but also there was a slight shift to L > R hemispheric predominance. Predominant L > R hemispheric differences in brain activation in normal subjects occurred in the order amyl acetate > menthone > pyridine, consistent with the hypothesis that pleasant odors are more appreciated in L hemisphere and unpleasant odors more in R hemisphere. Anterior frontal and temporal cortex regions previously found activated by imagination and smell of odors and phantosmia and phantogeusia perception accounted for most hemispheric differences.
-
Subjective visual perception: from local processing to emergent phenomena of brain activity.
Panagiotaropoulos, Theofanis I; Kapoor, Vishal; Logothetis, Nikos K
2014-05-05
The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.
-
Subjective visual perception: from local processing to emergent phenomena of brain activity
Panagiotaropoulos, Theofanis I.; Kapoor, Vishal; Logothetis, Nikos K.
2014-01-01
The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness. PMID:24639588
-
Birdsong and the neural production of steroids
Remage-Healey, Luke; London, Sarah E.; Schinger, Barney A.
2009-01-01
The forebrain circuits involved in singing and audition (the ‘song system’) in songbirds exhibit a remarkable capacity to synthesize and respond to steroid hormones. This review considers how local brain steroid production impacts the development, sexual differentiation, and activity of song system circuitry. The songbird forebrain contains all of the enzymes necessary for the de novo synthesis of steroids - including neuroestrogens - from cholesterol. Steroid production enzymes are found in neuronal cell bodies, but they are also expressed in pre-synaptic terminals in the song system, indicating a novel mode of brain steroid delivery to local circuits. The song system expresses nuclear hormone receptors, consistent with local action of brain-derived steroids. Local steroid production also occurs in brain regions that do not express nuclear hormone receptors, suggesting a non-classical mode-of-action. Recent evidence indicates that local steroid levels can change rapidly within the forebrain, in a manner similar to traditional neuromodulators. Lastly, we consider growing evidence for modulatory interactions between brain-derived steroids and neurotransmitter/neuropeptide networks within the song system. Songbirds have therefore emerged as a rich and powerful model system to explore the neural and neurochemical regulation of social behavior. PMID:19589382
-
Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain.
González de San Román, Estibaliz; Manuel, Iván; Giralt, María Teresa; Chun, Jerold; Estivill-Torrús, Guillermo; Rodríguez de Fonseca, Fernando; Santín, Luis Javier; Ferrer, Isidro; Rodríguez-Puertas, Rafael
2015-08-01
Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors: LPA1 -LPA6 . LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1 -null mice (a variant of LPA1 -null) lack [(35) S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCR), LPA1 to LPA6 . LPA evokes several responses in the central nervous system (CNS), including cortical development and folding, growth of the axonal cone and its retraction process. We used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 -binding sites in adult rodent and human brain. The distribution of LPA1 receptors in rat, mouse and human brains show the highest activity in white matter myelinated areas. The basal and LPA-evoked activities are abolished in MaLPA1 -null mice. The phospholipid precursors of LPA are localized by MALDI-IMS. The anatomical distribution of LPA precursors in rodent and human brain suggests a relationship with functional LPA1 receptors. © 2015 International Society for Neurochemistry.
-
Cerebral responses to local and global auditory novelty under general anesthesia
Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir
2017-01-01
Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046
-
Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu
2018-06-14
Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.
-
Riedl, Valentin; Bienkowska, Katarzyna; Strobel, Carola; Tahmasian, Masoud; Grimmer, Timo; Förster, Stefan; Friston, Karl J; Sorg, Christian; Drzezga, Alexander
2014-04-30
Over the last decade, synchronized resting-state fluctuations of blood oxygenation level-dependent (BOLD) signals between remote brain areas [so-called BOLD resting-state functional connectivity (rs-FC)] have gained enormous relevance in systems and clinical neuroscience. However, the neural underpinnings of rs-FC are still incompletely understood. Using simultaneous positron emission tomography/magnetic resonance imaging we here directly investigated the relationship between rs-FC and local neuronal activity in humans. Computational models suggest a mechanistic link between the dynamics of local neuronal activity and the functional coupling among distributed brain regions. Therefore, we hypothesized that the local activity (LA) of a region at rest determines its rs-FC. To test this hypothesis, we simultaneously measured both LA (glucose metabolism) and rs-FC (via synchronized BOLD fluctuations) during conditions of eyes closed or eyes open. During eyes open, LA increased in the visual system, and the salience network (i.e., cingulate and insular cortices) and the pattern of elevated LA coincided almost exactly with the spatial pattern of increased rs-FC. Specifically, the voxelwise regional profile of LA in these areas strongly correlated with the regional pattern of rs-FC among the same regions (e.g., LA in primary visual cortex accounts for ∼ 50%, and LA in anterior cingulate accounts for ∼ 20% of rs-FC with the visual system). These data provide the first direct evidence in humans that local neuronal activity determines BOLD FC at rest. Beyond its relevance for the neuronal basis of coherent BOLD signal fluctuations, our procedure may translate into clinical research particularly to investigate potentially aberrant links between local dynamics and remote functional coupling in patients with neuropsychiatric disorders.
-
Xu, Junhai; Yin, Xuntao; Ge, Haitao; Han, Yan; Pang, Zengchang; Tang, Yuchun; Liu, Baolin; Liu, Shuwei
2015-01-01
Attention is a crucial brain function for human beings. Using neuropsychological paradigms and task-based functional brain imaging, previous studies have indicated that widely distributed brain regions are engaged in three distinct attention subsystems: alerting, orienting and executive control (EC). Here, we explored the potential contribution of spontaneous brain activity to attention by examining whether resting-state activity could account for individual differences of the attentional performance in normal individuals. The resting-state functional images and behavioral data from attention network test (ANT) task were collected in 59 healthy subjects. Graph analysis was conducted to obtain the characteristics of functional brain networks and linear regression analyses were used to explore their relationships with behavioral performances of the three attentional components. We found that there was no significant relationship between the attentional performance and the global measures, while the attentional performance was associated with specific local regional efficiency. These regions related to the scores of alerting, orienting and EC largely overlapped with the regions activated in previous task-related functional imaging studies, and were consistent with the intrinsic dorsal and ventral attention networks (DAN/VAN). In addition, the strong associations between the attentional performance and specific regional efficiency suggested that there was a possible relationship between the DAN/VAN and task performances in the ANT. We concluded that the intrinsic activity of the human brain could reflect the processing efficiency of the attention system. Our findings revealed a robust evidence for the functional significance of the efficiently organized intrinsic brain network for highly productive cognitions and the hypothesized role of the DAN/VAN at rest.
-
Chaos in the brain: imaging via chaoticity of EEG/MEG signals
NASA Astrophysics Data System (ADS)
Kowalik, Zbigniew J.; Elbert, Thomas; Rockstroh, Brigitte; Hoke, Manfried
1995-03-01
Brain electro- (EEG) or magnetoencephalogram (MEG) can be analyzed by using methods of the nonlinear system theory. We show that even for very short and nonstationary time series it is possible to functionally differentiate various brain activities. Usually the analysis assumes that the analyzed signals are both long and stationary, so that the classic spectral methods can be used. Even more convincing results can be obtained under these circumstances when the dimensional analysis or estimation of the Kolmogorov entropy or the Lyapunov exponent are performed. When measuring the spontaneous activity of a human brain the assumption of stationarity is questionable and `static' methods (correlation dimension, entropy, etc.) are then not adequate. In this case `dynamic' methods like pointwise-D2 dimension or chaoticity measures should be applied. Predictability measures in the form of local Lyapunov exponents are capable of revealing directly the chaoticity of a given process, and can practically be applied for functional differentiation of brain activity. We exemplify these in cases of apallic syndrome, tinnitus and schizophrenia. We show that: the average chaoticity in apallic syndrome differentiates brain states both in space and time, chaoticity changes temporally in case of schizophrenia (critical jumps of chaoticity), chaoticity changes locally in space, i.e., in the cortex plane in case of tinnitus.
-
Chiang, Ann-Shyn; Lin, Chih-Yung; Chuang, Chao-Chun; Chang, Hsiu-Ming; Hsieh, Chang-Huain; Yeh, Chang-Wei; Shih, Chi-Tin; Wu, Jian-Jheng; Wang, Guo-Tzau; Chen, Yung-Chang; Wu, Cheng-Chi; Chen, Guan-Yu; Ching, Yu-Tai; Lee, Ping-Chang; Lin, Chih-Yang; Lin, Hui-Hao; Wu, Chia-Chou; Hsu, Hao-Wei; Huang, Yun-Ann; Chen, Jing-Yi; Chiang, Hsin-Jung; Lu, Chun-Fang; Ni, Ru-Fen; Yeh, Chao-Yuan; Hwang, Jenn-Kang
2011-01-11
Animal behavior is governed by the activity of interconnected brain circuits. Comprehensive brain wiring maps are thus needed in order to formulate hypotheses about information flow and also to guide genetic manipulations aimed at understanding how genes and circuits orchestrate complex behaviors. To assemble this map, we deconstructed the adult Drosophila brain into approximately 16,000 single neurons and reconstructed them into a common standardized framework to produce a virtual fly brain. We have constructed a mesoscopic map and found that it consists of 41 local processing units (LPUs), six hubs, and 58 tracts covering the whole Drosophila brain. Despite individual local variation, the architecture of the Drosophila brain shows invariance for both the aggregation of local neurons (LNs) within specific LPUs and for the connectivity of projection neurons (PNs) between the same set of LPUs. An open-access image database, named FlyCircuit, has been constructed for online data archiving, mining, analysis, and three-dimensional visualization of all single neurons, brain-wide LPUs, their wiring diagrams, and neural tracts. We found that the Drosophila brain is assembled from families of multiple LPUs and their interconnections. This provides an essential first step in the analysis of information processing within and between neurons in a complete brain. Copyright © 2011 Elsevier Ltd. All rights reserved.
-
Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang
2018-06-01
Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.
-
Verrel, Julius; Almagor, Eilat; Schumann, Frank; Lindenberger, Ulman; Kühn, Simone
2015-01-01
We use functional magnetic resonance imaging to investigate short-term neural effects of a brief sensorimotor intervention adapted from the Feldenkrais method, a movement-based learning method. Twenty-one participants (10 men, 19–30 years) took part in the study. Participants were in a supine position in the scanner with extended legs while an experienced Feldenkrais practitioner used a planar board to touch and apply minimal force to different parts of the sole and toes of their left foot under two experimental conditions. In the local condition, the practitioner explored movement within foot and ankle. In the global condition, the practitioner focused on the connection and support from the foot to the rest of the body. Before (baseline) and after each intervention (post-local, post-global), we measured brain activity during intermittent pushing/releasing with the left leg and during resting state. Independent localizer tasks were used to identify regions of interest (ROI). Brain activity during left-foot pushing did not significantly differ between conditions in sensorimotor areas. Resting state activity (regional homogeneity, ReHo) increased from baseline to post-local in medial right motor cortex, and from baseline to post-global in the left supplementary/cingulate motor area. Contrasting post-global to post-local showed higher ReHo in right lateral motor cortex. ROI analyses showed significant increases in ReHo in pushing-related areas from baseline to both post-local and post-global, and this increase tended to be more pronounced post-local. The results of this exploratory study show that a short, non-intrusive sensorimotor intervention can have short-term effects on spontaneous cortical activity in functionally related brain regions. Increased resting state activity in higher-order motor areas supports the hypothesis that the global intervention engages action-related neural processes. PMID:25972804
-
Ng, Tommy H B; Sowman, Paul F; Brock, Jon; Johnson, Blake W
2013-02-01
During bimanual load lifting, the brain must anticipate the effects of unloading upon the load-bearing arm. Little is currently known about the neural networks that coordinate these anticipatory postural adjustments. We measured neuromagnetic brain activity with whole-head magnetoencephalography while participants performed a bimanual load-lifting task. Anticipatory adjustments were associated with reduction in biceps brachii muscle activity of the load-bearing arm and pre-movement desynchronization of the cortical beta rhythm. Beamforming analyses localized anticipatory brain activity to the precentral gyrus, basal ganglia, supplementary motor area, and thalamus, contralateral to the load-bearing arm. To our knowledge this is the first human neuroimaging study to directly investigate anticipatory postural adjustments and to explicitly partition the anticipatory and volitional aspects of brain activity in bimanual load lifting. These data contribute to our understanding of the neural systems supporting anticipatory postural adjustments in healthy adults. Copyright © 2012 Elsevier Inc. All rights reserved.
-
Whole-brain activity mapping onto a zebrafish brain atlas.
Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F
2015-11-01
In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.
-
Increased resting-state brain entropy in Alzheimer's disease.
Xue, Shao-Wei; Guo, Yonghu
2018-03-07
Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.
-
Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.
Kiyatkin, Eugene A; Wakabayashi, Ken T
2015-01-21
Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.
-
Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter
2016-05-01
Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
-
Pesaran, Bijan; Vinck, Martin; Einevoll, Gaute T; Sirota, Anton; Fries, Pascal; Siegel, Markus; Truccolo, Wilson; Schroeder, Charles E; Srinivasan, Ramesh
2018-06-25
New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (electroencephalograms, magnetoencephalograms, electrocorticograms and local field potentials) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide recommendations for interpreting the data using forward and inverse models. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems.
-
NASA Astrophysics Data System (ADS)
Yuan, Yi; Chen, Yudong; Li, Xiaoli
2016-02-01
A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.
-
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor
NASA Astrophysics Data System (ADS)
Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.
2016-06-01
The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.
-
Renier, Laurent A.; Anurova, Irina; De Volder, Anne G.; Carlson, Synnöve; VanMeter, John; Rauschecker, Josef P.
2012-01-01
The segregation between cortical pathways for the identification and localization of objects is thought of as a general organizational principle in the brain. Yet, little is known about the unimodal versus multimodal nature of these processing streams. The main purpose of the present study was to test whether the auditory and tactile dual pathways converged into specialized multisensory brain areas. We used functional magnetic resonance imaging (fMRI) to compare directly in the same subjects the brain activation related to localization and identification of comparable auditory and vibrotactile stimuli. Results indicate that the right inferior frontal gyrus (IFG) and both left and right insula were more activated during identification conditions than during localization in both touch and audition. The reverse dissociation was found for the left and right inferior parietal lobules (IPL), the left superior parietal lobule (SPL) and the right precuneus-SPL, which were all more activated during localization conditions in the two modalities. We propose that specialized areas in the right IFG and the left and right insula are multisensory operators for the processing of stimulus identity whereas parts of the left and right IPL and SPL are specialized for the processing of spatial attributes independently of sensory modality. PMID:19726653
-
NASA Astrophysics Data System (ADS)
Lin, Juan; Liu, Chenglian; Guo, Yongning
2014-10-01
The estimation of neural active sources from the magnetoencephalography (MEG) data is a very critical issue for both clinical neurology and brain functions research. A widely accepted source-modeling technique for MEG involves calculating a set of equivalent current dipoles (ECDs). Depth in the brain is one of difficulties in MEG source localization. Particle swarm optimization(PSO) is widely used to solve various optimization problems. In this paper we discuss its ability and robustness to find the global optimum in different depths of the brain when using single equivalent current dipole (sECD) model and single time sliced data. The results show that PSO is an effective global optimization to MEG source localization when given one dipole in different depths.
-
Analysis of fMRI data using noise-diffusion network models: a new covariance-coding perspective.
Gilson, Matthieu
2018-04-01
Since the middle of the 1990s, studies of resting-state fMRI/BOLD data have explored the correlation patterns of activity across the whole brain, which is referred to as functional connectivity (FC). Among the many methods that have been developed to interpret FC, a recently proposed model-based approach describes the propagation of fluctuating BOLD activity within the recurrently connected brain network by inferring the effective connectivity (EC). In this model, EC quantifies the strengths of directional interactions between brain regions, viewed from the proxy of BOLD activity. In addition, the tuning procedure for the model provides estimates for the local variability (input variances) to explain how the observed FC is generated. Generalizing, the network dynamics can be studied in the context of an input-output mapping-determined by EC-for the second-order statistics of fluctuating nodal activities. The present paper focuses on the following detection paradigm: observing output covariances, how discriminative is the (estimated) network model with respect to various input covariance patterns? An application with the model fitted to experimental fMRI data-movie viewing versus resting state-illustrates that changes in local variability and changes in brain coordination go hand in hand.
-
In vivo recordings of brain activity using organic transistors
Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G.
2013-01-01
In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications. PMID:23481383
-
In vivo recordings of brain activity using organic transistors.
Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G
2013-01-01
In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications.
-
Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu
2015-05-01
The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.
-
Bachelot, Thomas; Le Rhun, Emilie; Labidi-Gally, Intidar; Heudel, Pierre; Gilabert, Marine; Bonneterre, Jacques; Pierga, Jean-Yves; Gonçalves, Anthony
2013-01-01
Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases.
-
Sakurai, Yoshio
2014-01-01
This perspective emphasizes that the brain-machine interface (BMI) research has the potential to clarify major mysteries of the brain and that such clarification of the mysteries by neuroscience is needed to develop BMIs. I enumerate five principal mysteries. The first is “how is information encoded in the brain?” This is the fundamental question for understanding what our minds are and is related to the verification of Hebb’s cell assembly theory. The second is “how is information distributed in the brain?” This is also a reconsideration of the functional localization of the brain. The third is “what is the function of the ongoing activity of the brain?” This is the problem of how the brain is active during no-task periods and what meaning such spontaneous activity has. The fourth is “how does the bodily behavior affect the brain function?” This is the problem of brain-body interaction, and obtaining a new “body” by a BMI leads to a possibility of changes in the owner’s brain. The last is “to what extent can the brain induce plasticity?” Most BMIs require changes in the brain’s neuronal activity to realize higher performance, and the neuronal operant conditioning inherent in the BMIs further enhances changes in the activity. PMID:24904323
-
Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel
2017-01-01
Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.
-
Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel
2017-01-01
Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854
-
Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients
Chang, Won Hyuk; Kim, Yun-Hee; Lee, Seong-Whan; Kwon, Gyu Hyun
2015-01-01
Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke. PMID:26656269
-
Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir
2016-01-01
Abstract Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. PMID:27017189
-
Mercier, Manuel R; Schwartz, Sophie; Spinelli, Laurent; Michel, Christoph M; Blanke, Olaf
2017-03-01
The main model of visual processing in primates proposes an anatomo-functional distinction between the dorsal stream, specialized in spatio-temporal information, and the ventral stream, processing essentially form information. However, these two pathways also communicate to share much visual information. These dorso-ventral interactions have been studied using form-from-motion (FfM) stimuli, revealing that FfM perception first activates dorsal regions (e.g., MT+/V5), followed by successive activations of ventral regions (e.g., LOC). However, relatively little is known about the implications of focal brain damage of visual areas on these dorso-ventral interactions. In the present case report, we investigated the dynamics of dorsal and ventral activations related to FfM perception (using topographical ERP analysis and electrical source imaging) in a patient suffering from a deficit in FfM perception due to right extrastriate brain damage in the ventral stream. Despite the patient's FfM impairment, both successful (observed for the highest level of FfM signal) and absent/failed FfM perception evoked the same temporal sequence of three processing states observed previously in healthy subjects. During the first period, brain source localization revealed cortical activations along the dorsal stream, currently associated with preserved elementary motion processing. During the latter two periods, the patterns of activity differed from normal subjects: activations were observed in the ventral stream (as reported for normal subjects), but also in the dorsal pathway, with the strongest and most sustained activity localized in the parieto-occipital regions. On the other hand, absent/failed FfM perception was characterized by weaker brain activity, restricted to the more lateral regions. This study shows that in the present case report, successful FfM perception, while following the same temporal sequence of processing steps as in normal subjects, evoked different patterns of brain activity. By revealing a brain circuit involving the most rostral part of the dorsal pathway, this study provides further support for neuro-imaging studies and brain lesion investigations that have suggested the existence of different brain circuits associated with different profiles of interaction between the dorsal and the ventral streams.
-
Zhang, Myron; Avitsian, Rafi; Bhattacharyya, Pallab; Bulacio, Juan; Cendes, Fernando; Enatsu, Rei; Lowe, Mark; Najm, Imad; Nair, Dileep; Phillips, Michael; Gonzalez-Martinez, Jorge
2014-01-01
Abstract Patients with medically intractable epilepsy often undergo invasive evaluation and surgery, with a 50% success rate. The low success rate is likely due to poor identification of the epileptogenic zone (EZ), the brain area causing seizures. This work introduces a new method using functional magnetic resonance imaging (fMRI) with simultaneous direct electrical stimulation of the brain that could help localize the EZ, performed in five patients with medically intractable epilepsy undergoing invasive evaluation with intracranial depth electrodes. Stimulation occurred in a location near the hypothesized EZ and a location away. Electrical recordings in response to stimulation were recorded and compared to fMRI. Multiple stimulation parameters were varied, like current and frequency. The brain areas showing fMRI response were compared with the areas resected and the success of surgery. Robust fMRI maps of activation networks were easily produced, which also showed a significant but weak positive correlation between quantitative measures of blood-oxygen-level-dependent (BOLD) activity and measures of electrical activity in response to direct electrical stimulation (mean correlation coefficient of 0.38 for all acquisitions that produced a strong BOLD response). For four patients with outcome data at 6 months, successful surgical outcome is consistent with the resection of brain areas containing high local fMRI activity. In conclusion, this method demonstrates the feasibility of simultaneous direct electrical stimulation and fMRI in humans, which allows the study of brain connectivity with high resolution and full spatial coverage. This innovative technique could be used to better define the localization and extension of the EZ in intractable epilepsies, as well as for other functional neurosurgical procedures. PMID:24735069
-
[Local brain activity in different motor subtypes of Parkinson's disease with fMRI].
Hou, Ya'nan; Zhang, Jiarong; Chen, Biao; Wu, Tao
2015-02-17
To explore the changes of local brain activity in motor subtypes of Parkinson's disease (PD) with functional magnetic resonance imaging (fMRI). A total of 60 idiopathic PD and 30 age- and gender-matched normal controls were examined with resting-state fMRI from January 2013 to March 2014. All subjects gave their written informed consent for the study. The amplitude of low-frequency fluctuation (ALFF) was calculated to measure local brain activity. The PD patients were divided into two groups of tremor dominant (TD) and postural instability/gait difficulty (PIGD) (n = 30 each). All subjects gave their written in formed consent for the study.One-way ANOVA and post-hoc t-test were performed to detect the differences of local brain activity between PD and normal subjects. And the correlations were examined between ALFF, scores and levodopa dose. Compared with normal subjects, the TD group showed increased activity in bilateral cerebellums (-37, -47, -38), thalamus (-18, -17,0), pons (-3, -23, -37) and left precentral gyrus (-41, -30, 46) versus decreased activity in bilateral frontal lobes (-13, 69, 6), temporal lobes (-42, 18, -21), left insula (-32, 22, 2) and left anterior cingulated (-7, 32, -5). The PIGD group showed increased activity in right postcentral gyrus (63, -18, 39) and decreased activity in bilateral putamens (-24, 12, 3), pre-supplementary motor area (10, 10, 58), frontal lobes (15, -15, 57), temporal lobes (-39, 18, -3) and left insula (-29, 20, 11). Compared with PIGD, the TD group showed increased activity in temporal lobes, but decreased activity in frontal lobes. Additionally, ALFF in bilateral cerebellums and frontal lobes was positively correlated with TD scores while ALFF in left precentral gyrus, bilateral putamens and temporal lobes negatively correlated with TD scores. ALFF in bilateral frontal lobes and left temporal lobe was positively correlated with PIGD scores.However, in right postcentral gyrus and bilateral putamens, ALFF was negatively correlated with PIGD scores. The levodopa dose was positively correlated with frontal lobes and temporal lobe in TD and cerebellums and inferior parietal lobule in PIGD. A specific pattern of intrinsic activity in TD and PIGD may provide insights into neurophysiological mechanisms of PD motor subtypes. The changes of brain activity in TD are caused by the interaction between cerebello-thalamo-cortical circuit and basal ganglia loop while the changes in PIGD result largely from damaged basal ganglia loop.
-
Association Between Brain Activation and Functional Connectivity.
Tomasi, Dardo; Volkow, Nora D
2018-04-13
The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.
-
Nanoscale effects in dendrimer-mediated targeting of neuroinflammation
Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K.; Zhang, Zhi; Kambhampati, Siva P.; Kannan, Rangaramanujam M.; Kannan, Sujatha
2017-01-01
Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. PMID:27267631
-
Mapping Epileptic Activity: Sources or Networks for the Clinicians?
Pittau, Francesca; Mégevand, Pierre; Sheybani, Laurent; Abela, Eugenio; Grouiller, Frédéric; Spinelli, Laurent; Michel, Christoph M.; Seeck, Margitta; Vulliemoz, Serge
2014-01-01
Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity. PMID:25414692
-
Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.
Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K; Zhang, Zhi; Kambhampati, Siva P; Kannan, Rangaramanujam M; Kannan, Sujatha
2016-09-01
Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Measurable benefits on brain activity from the practice of educational leisure.
Requena, Carmen; López, Verónica
2014-01-01
Even if behavioral studies relate leisure practices to the preservation of memory in old persons, there is unsubstantial evidence of the import of leisure on brain activity. This study was to compare the brain activity of elderly retired people who engage in different types of leisure activities. Quasi-experimental study over a sample of 60 elderly, retired subjects distributed into three groups according to the leisure activities they practised: educational leisure (G1), memory games (G2), and card games (G3). Applied measures include the conceptual distinction between free time and leisure, the test of the organization of free time measuring 24 clock divisions, and EEG register during 12 word list memorizing. The results show that the type of leisure activity is associated with significant quantitative differences regarding the use of free time. G1 devotes more time to leisure activities than G2 (p = 0.007) and G3 (p = 0.034). G1 rests more actively than the other two groups (p = 0.001). The electrical localization of brain activity indicated a reverse tendency of activation according to the bands and groups. Engaging in educational leisure activities is a useful practice to protect healthy brain compensation strategies. Future longitudinal research may verify the causal relation between practicing educational leisure activities and functional brain aging.
-
Bettinardi, Ruggero G.; Tort-Colet, Núria; Ruiz-Mejias, Marcel; Sanchez-Vives, Maria V.; Deco, Gustavo
2015-01-01
Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex. PMID:25804643
-
Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.
Dmochowski, Jacek P; Koessler, Laurent; Norcia, Anthony M; Bikson, Marom; Parra, Lucas C
2017-08-15
To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
-
Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation
Dmochowski, Jacek P.; Koessler, Laurent; Norcia, Anthony M.; Bikson, Marom; Parra, Lucas C.
2018-01-01
To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4–7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. PMID:28578130
-
Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI☆
Koush, Yury; Rosa, Maria Joao; Robineau, Fabien; Heinen, Klaartje; W. Rieger, Sebastian; Weiskopf, Nikolaus; Vuilleumier, Patrik; Van De Ville, Dimitri; Scharnowski, Frank
2013-01-01
Neurofeedback based on real-time fMRI is an emerging technique that can be used to train voluntary control of brain activity. Such brain training has been shown to lead to behavioral effects that are specific to the functional role of the targeted brain area. However, real-time fMRI-based neurofeedback so far was limited to mainly training localized brain activity within a region of interest. Here, we overcome this limitation by presenting near real-time dynamic causal modeling in order to provide feedback information based on connectivity between brain areas rather than activity within a single brain area. Using a visual–spatial attention paradigm, we show that participants can voluntarily control a feedback signal that is based on the Bayesian model comparison between two predefined model alternatives, i.e. the connectivity between left visual cortex and left parietal cortex vs. the connectivity between right visual cortex and right parietal cortex. Our new approach thus allows for training voluntary control over specific functional brain networks. Because most mental functions and most neurological disorders are associated with network activity rather than with activity in a single brain region, this novel approach is an important methodological innovation in order to more directly target functionally relevant brain networks. PMID:23668967
-
Two hands, one brain, and aging.
Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P
2017-04-01
Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Whole-brain activity mapping onto a zebrafish brain atlas
Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.
2015-01-01
In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924
-
Owen, Julia P; Wipf, David P; Attias, Hagai T; Sekihara, Kensuke; Nagarajan, Srikantan S
2012-03-01
In this paper, we present an extensive performance evaluation of a novel source localization algorithm, Champagne. It is derived in an empirical Bayesian framework that yields sparse solutions to the inverse problem. It is robust to correlated sources and learns the statistics of non-stimulus-evoked activity to suppress the effect of noise and interfering brain activity. We tested Champagne on both simulated and real M/EEG data. The source locations used for the simulated data were chosen to test the performance on challenging source configurations. In simulations, we found that Champagne outperforms the benchmark algorithms in terms of both the accuracy of the source localizations and the correct estimation of source time courses. We also demonstrate that Champagne is more robust to correlated brain activity present in real MEG data and is able to resolve many distinct and functionally relevant brain areas with real MEG and EEG data. Copyright © 2011 Elsevier Inc. All rights reserved.
-
Functional magnetic resonance imaging reflects changes in brain functioning with sedation.
Starbuck, Victoria N; Kay, Gary G; Platenberg, R. Craig; Lin, Chin-Shoou; Zielinski, Brandon A
2000-12-01
Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd.
-
The Use of Magnetoencephalography in Evaluating Human Performance
1991-06-01
determines the head cartesian coordinate system, and calculates the locations of the dipole sets in this reference frame. This system is based on an optical ...differences in brain activity are found between imagers and nonimagers , the brain areas which seem to be involved will be localized. 25 3. The poor
-
Truncated RAP-MUSIC (TRAP-MUSIC) for MEG and EEG source localization.
Mäkelä, Niko; Stenroos, Matti; Sarvas, Jukka; Ilmoniemi, Risto J
2018-02-15
Electrically active brain regions can be located applying MUltiple SIgnal Classification (MUSIC) on magneto- or electroencephalographic (MEG; EEG) data. We introduce a new MUSIC method, called truncated recursively-applied-and-projected MUSIC (TRAP-MUSIC). It corrects a hidden deficiency of the conventional RAP-MUSIC algorithm, which prevents estimation of the true number of brain-signal sources accurately. The correction is done by applying a sequential dimension reduction to the signal-subspace projection. We show that TRAP-MUSIC significantly improves the performance of MUSIC-type localization; in particular, it successfully and robustly locates active brain regions and estimates their number. We compare TRAP-MUSIC and RAP-MUSIC in simulations with varying key parameters, e.g., signal-to-noise ratio, correlation between source time-courses, and initial estimate for the dimension of the signal space. In addition, we validate TRAP-MUSIC with measured MEG data. We suggest that with the proposed TRAP-MUSIC method, MUSIC-type localization could become more reliable and suitable for various online and offline MEG and EEG applications. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Age-related functional brain changes in young children.
Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine
2017-07-15
Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Source localization of brain activity using helium-free interferometer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dammers, Jürgen, E-mail: J.Dammers@fz-juelich.de; Chocholacs, Harald; Eich, Eberhard
2014-05-26
To detect extremely small magnetic fields generated by the human brain, currently all commercial magnetoencephalography (MEG) systems are equipped with low-temperature (low-T{sub c}) superconducting quantum interference device (SQUID) sensors that use liquid helium for cooling. The limited and increasingly expensive supply of helium, which has seen dramatic price increases recently, has become a real problem for such systems and the situation shows no signs of abating. MEG research in the long run is now endangered. In this study, we report a MEG source localization utilizing a single, highly sensitive SQUID cooled with liquid nitrogen only. Our findings confirm that localizationmore » of neuromagnetic activity is indeed possible using high-T{sub c} SQUIDs. We believe that our findings secure the future of this exquisitely sensitive technique and have major implications for brain research and the developments of cost-effective multi-channel, high-T{sub c} SQUID-based MEG systems.« less
-
Oscillatory brain activity in spontaneous and induced sleep stages in flies.
Yap, Melvyn H W; Grabowska, Martyna J; Rohrscheib, Chelsie; Jeans, Rhiannon; Troup, Michael; Paulk, Angelique C; van Alphen, Bart; Shaw, Paul J; van Swinderen, Bruno
2017-11-28
Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABA A agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.
-
Florin, Esther; Baillet, Sylvain
2015-01-01
Functional imaging of the resting brain consistently reveals broad motifs of correlated blood oxygen level dependent (BOLD) activity that engage cerebral regions from distinct functional systems. Yet, the neurophysiological processes underlying these organized, large-scale fluctuations remain to be uncovered. Using magnetoencephalography (MEG) imaging during rest in 12 healthy subjects we analyse the resting state networks and their underlying neurophysiology. We first demonstrate non-invasively that cortical occurrences of high-frequency oscillatory activity are conditioned to the phase of slower spontaneous fluctuations in neural ensembles. We further show that resting-state networks emerge from synchronized phase-amplitude coupling across the brain. Overall, these findings suggest a unified principle of local-to-global neural signaling for long-range brain communication. PMID:25680519
-
NASA Astrophysics Data System (ADS)
Baseri, Babak; Choi, James J.; Deffieux, Thomas; Samiotaki, Gesthimani; Tung, Yao-Sheng; Olumolade, Oluyemi; Small, Scott A.; Morrison, Barclay, III; Konofagou, Elisa E.
2012-04-01
The brain-derived neurotrophic factor (BDNF) has been shown to have broad neuroprotective effects in addition to its therapeutic role in neurodegenerative disease. In this study, the efficacy of delivering exogenous BDNF to the left hippocampus is demonstrated in wild-type mice (n = 7) through the noninvasively disrupted blood-brain barrier (BBB) using focused ultrasound (FUS). The BDNF bioactivity was found to be preserved following delivery as assessed quantitatively by immunohistochemical detection of the pTrkB receptor and activated pAkt, pMAPK, and pCREB in the hippocampal neurons. It was therefore shown for the first time that systemically administered neurotrophic factors can cross the noninvasively disrupted BBB and trigger neuronal downstream signaling effects in a highly localized region in the brain. This is the first time that the administered molecule is tracked through the BBB and localized in the neuron triggering molecular effects. Additional preliminary findings are shown in wild-type mice with two additional neurotrophic factors such as the glia-derived neurotrophic factor (n = 12) and neurturin (n = 2). This further demonstrates the impact of FUS for the early treatment of CNS diseases at the cellular and molecular level and strengthens its premise for FUS-assisted drug delivery and efficacy.
-
Cornil, C. A.; Dalla, C.; Papadopoulou-Daifoti, Z.; Baillien, M.; Dejace, C.; Ball, G.F.; Balthazart, J.
2014-01-01
In Japanese quail as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increases dopamine release in the preoptic area. In quail, in vitro brain aromatase activity is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, while a single injection of the aromatase inhibitor Vorozole™ rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain aromatase activity that was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that aromatase activity is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activity. These data challenges established views about the causal relationships among dopamine, estrogen action and male sexual behavior. PMID:15932925
-
Effect of x-radiation to brain on cerebral glucose utilization in the rat.
D'Aquino, S; Cicciarello, R; D'Avella, D; Mesiti, M; Albiero, F; Princi, P; Gagliardi, M E; Russi, E; D'Aquino, A
1990-01-01
We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.
-
Wavelet-based localization of oscillatory sources from magnetoencephalography data.
Lina, J M; Chowdhury, R; Lemay, E; Kobayashi, E; Grova, C
2014-08-01
Transient brain oscillatory activities recorded with Eelectroencephalography (EEG) or magnetoencephalography (MEG) are characteristic features in physiological and pathological processes. This study is aimed at describing, evaluating, and illustrating with clinical data a new method for localizing the sources of oscillatory cortical activity recorded by MEG. The method combines time-frequency representation and an entropic regularization technique in a common framework, assuming that brain activity is sparse in time and space. Spatial sparsity relies on the assumption that brain activity is organized among cortical parcels. Sparsity in time is achieved by transposing the inverse problem in the wavelet representation, for both data and sources. We propose an estimator of the wavelet coefficients of the sources based on the maximum entropy on the mean (MEM) principle. The full dynamics of the sources is obtained from the inverse wavelet transform, and principal component analysis of the reconstructed time courses is applied to extract oscillatory components. This methodology is evaluated using realistic simulations of single-trial signals, combining fast and sudden discharges (spike) along with bursts of oscillating activity. The method is finally illustrated with a clinical application using MEG data acquired on a patient with a right orbitofrontal epilepsy.
-
Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI
Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng
2016-01-01
Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860
-
Brain Interaction during Cooperation: Evaluating Local Properties of Multiple-Brain Network.
Sciaraffa, Nicolina; Borghini, Gianluca; Aricò, Pietro; Di Flumeri, Gianluca; Colosimo, Alfredo; Bezerianos, Anastasios; Thakor, Nitish V; Babiloni, Fabio
2017-07-21
Subjects' interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental effort required by subjects while facing a situation that is getting harder, that is, mental workload, to define an objective measure based on how and if team members are interacting is not so straightforward. In this study, behavioral, subjective and synchronized electroencephalographic data were collected from couples involved in a cooperative task to describe the relationship between task difficulty and team coordination, in the sense of interaction aimed at cooperatively performing the assignment. Multiple-brain connectivity analysis provided information about the whole interacting system. The results showed that averaged local properties of a brain network were affected by task difficulty. In particular, strength changed significantly with task difficulty and clustering coefficients strongly correlated with the workload itself. In particular, a higher workload corresponded to lower clustering values over the central and parietal brain areas. Such results has been interpreted as less efficient organization of the network when the subjects' activities, due to high workload tendencies, were less coordinated.
-
He, De-Hua; Zhang, Liang-Min; Lin, Li-Ming; Ning, Ruo-Bing; Wang, Hua-Jun; Xu, Chang-Sheng; Lin, Jin-Xiu
2014-02-01
Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate ⅰ) whether short‑ and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ⅱ) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week‑old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short‑ and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short‑ and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive populations in order to prevent BP-linked brain damage.
-
Parsing Glucose Entry into the Brain: Novel Findings Obtained with Enzyme-Based Glucose Biosensors
2015-01-01
Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between “active” and “passive” glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the “neuronal” hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism. PMID:25490002
-
Lapborisuth, Pawan; Zhang, Xian; Noah, Adam; Hirsch, Joy
2017-04-01
Neurofeedback is a method for using neural activity displayed on a computer to regulate one's own brain function and has been shown to be a promising technique for training individuals to interact with brain-machine interface applications such as neuroprosthetic limbs. The goal of this study was to develop a user-friendly functional near-infrared spectroscopy (fNIRS)-based neurofeedback system to upregulate neural activity associated with motor imagery, which is frequently used in neuroprosthetic applications. We hypothesized that fNIRS neurofeedback would enhance activity in motor cortex during a motor imagery task. Twenty-two participants performed active and imaginary right-handed squeezing movements using an elastic ball while wearing a 98-channel fNIRS device. Neurofeedback traces representing localized cortical hemodynamic responses were graphically presented to participants in real time. Participants were instructed to observe this graphical representation and use the information to increase signal amplitude. Neural activity was compared during active and imaginary squeezing with and without neurofeedback. Active squeezing resulted in activity localized to the left premotor and supplementary motor cortex, and activity in the motor cortex was found to be modulated by neurofeedback. Activity in the motor cortex was also shown in the imaginary squeezing condition only in the presence of neurofeedback. These findings demonstrate that real-time fNIRS neurofeedback is a viable platform for brain-machine interface applications.
-
Effective connectivity of facial expression network by using Granger causality analysis
NASA Astrophysics Data System (ADS)
Zhang, Hui; Li, Xiaoting
2013-10-01
Functional magnetic resonance imaging (fMRI) is an advanced non-invasive data acquisition technique to investigate the neural activity in human brain. In addition to localize the functional brain regions that is activated by specific cognitive task, fMRI can also be utilized to measure the task-related functional interactions among the active regions of interest (ROI) in the brain. Among the variety of analysis tools proposed for modeling the connectivity of brain regions, Granger causality analysis (GCA) measure the directions of information interactions by looking for the lagged effect among the brain regions. In this study, we use fMRI and Granger Causality analysis to investigate the effective connectivity of brain network induced by viewing several kinds of expressional faces. We focus on four kinds of facial expression stimuli: fearful, angry, happy and neutral faces. Five face selective regions of interest are localized and the effective connectivity within these regions is measured for the expressional faces. Our result based on 8 subjects showed that there is significant effective connectivity from STS to amygdala, from amygdala to OFA, aFFA and pFFA, from STS to aFFA and from pFFA to aFFA. This result suggested that there is an information flow from the STS to the amygdala when perusing expressional faces. This emotional expressional information flow that is conveyed by STS and amygdala, flow back to the face selective regions in occipital-temporal lobes, which constructed a emotional face processing network.
-
Wyczesany, Miroslaw; Ligeza, Tomasz S
2015-03-01
The locationist model of affect, which assumes separate brain structures devoted to particular discrete emotions, is currently being questioned as it has not received enough convincing experimental support. An alternative, constructionist approach suggests that our emotional states emerge from the interaction between brain functional networks, which are related to more general, continuous affective categories. In the study, we tested whether the three-dimensional model of affect based on valence, arousal, and dominance (VAD) can reflect brain activity in a more coherent way than the traditional locationist approach. Independent components of brain activity were derived from spontaneous EEG recordings and localized using the DIPFIT method. The correspondence between the spectral power of the revealed brain sources and a mood self-report quantified on the VAD space was analysed. Activation of four (out of nine) clusters of independent brain sources could be successfully explained by the specific combination of three VAD dimensions. The results support the constructionist theory of emotions.
-
Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro
2012-11-01
Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT(1)) receptor (AT(1)R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using (11)C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Three male rhesus macaques were bolus intravenously administered [(11)C]telmisartan either alone or as a mixture with unlabeled telmisartan (1mg/kg). Dynamic PET images were acquired for 95min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Telmisartan penetrated into the brain little but enough to block AT(1)R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT(1)R distribution was noted over the entire brain, even on tracer alone dosing. Telmisartan penetrated into the brain enough to block AT(1)R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs. Copyright © 2012 Elsevier Inc. All rights reserved.
-
Pai, Vaibhav P; Lemire, Joan M; Chen, Ying; Lin, Gufa; Levin, Michael
2015-01-01
Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.
-
Berman, Brian D.; Horovitz, Silvina G.; Venkataraman, Gaurav; Hallett, Mark
2011-01-01
Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. PMID:21803163
-
Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.
Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos
2016-03-01
Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.
-
The physics of functional magnetic resonance imaging (fMRI)
NASA Astrophysics Data System (ADS)
Buxton, Richard B.
2013-09-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.
-
The physics of functional magnetic resonance imaging (fMRI)
Buxton, Richard B
2015-01-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm3 spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology. PMID:24006360
-
The physics of functional magnetic resonance imaging (fMRI).
Buxton, Richard B
2013-09-01
Functional magnetic resonance imaging (fMRI) is a methodology for detecting dynamic patterns of activity in the working human brain. Although the initial discoveries that led to fMRI are only about 20 years old, this new field has revolutionized the study of brain function. The ability to detect changes in brain activity has a biophysical basis in the magnetic properties of deoxyhemoglobin, and a physiological basis in the way blood flow increases more than oxygen metabolism when local neural activity increases. These effects translate to a subtle increase in the local magnetic resonance signal, the blood oxygenation level dependent (BOLD) effect, when neural activity increases. With current techniques, this pattern of activation can be measured with resolution approaching 1 mm(3) spatially and 1 s temporally. This review focuses on the physical basis of the BOLD effect, the imaging methods used to measure it, the possible origins of the physiological effects that produce a mismatch of blood flow and oxygen metabolism during neural activation, and the mathematical models that have been developed to understand the measured signals. An overarching theme is the growing field of quantitative fMRI, in which other MRI methods are combined with BOLD methods and analyzed within a theoretical modeling framework to derive quantitative estimates of oxygen metabolism and other physiological variables. That goal is the current challenge for fMRI: to move fMRI from a mapping tool to a quantitative probe of brain physiology.
-
Barraza, Paulo; Chavez, Mario; Rodríguez, Eugenio
2016-01-01
Similar to linguistic stimuli, music can also prime the meaning of a subsequent word. However, it is so far unknown what is the brain dynamics underlying the semantic priming effect induced by music, and its relation to language. To elucidate these issues, we compare the brain oscillatory response to visual words that have been semantically primed either by a musical excerpt or by an auditory sentence. We found that semantic violation between music-word pairs triggers a classical ERP N400, and induces a sustained increase of long-distance theta phase synchrony, along with a transient increase of local gamma activity. Similar results were observed after linguistic semantic violation except for gamma activity, which increased after semantic congruence between sentence-word pairs. Our findings indicate that local gamma activity is a neural marker that signals different ways of semantic processing between music and language, revealing the dynamic and self-organized nature of the semantic processing. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Anatomical Location of LPA1 Activation and LPA Phospholipid Precursors in Rodent and Human Brain
González de San Román, E; Manuel, I; Giralt, MT; Chun, J; Estivill-Torrús, G; Rodriguez de Fonseca, F; Santín, LJ; Ferrer, I; Rodriguez-Puertas, R
2016-01-01
Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCRs): LPA1–LPA6. LPA evokes several responses in the CNS including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [35S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1-null mice (a variant of LPA1-null) lack [35S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides (PA) and phosphatidylcholines (PC). Both PA and PC species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. PMID:25857358
-
Breaking ignorance: the case of the brain.
Wekerle, H
2006-01-01
Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status: they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B cells also contact CNS-like structures outside of the brain. Then pathological processes such as neurodegeneration commonly lift the brain's immune privilege, shifting the local milieus from immune-hostile to immune-friendly. Finally, brain-reactive T cells, which abound in the healthy immune repertoire, but remain innocuous throughout life, can be activated and gain access to their target tissues. On their way, they take an ordered migration through peripheral lymphoid tissues and blood circulation, and undergo a profound reprogramming of their gene expression profile, which renders them fit to enter the nervous system and to interact with local cellule elements.
-
[Cognitive advantages of the third age: a neural network model of brain aging].
Karpenko, M P; Kachalova, L M; Budilova, E V; Terekhin, A T
2009-01-01
We consider a neural network model of age-related cognitive changes in aging brain based on Hopfield network with a sigmoid function of neuron activation. Age is included in the activation function as a parameter in the form of exponential rate denominator, which makes it possible to take into account the weakening of interneuronal links really observed in the aging brain. Analysis of properties of the Lyapunov function associated with the network shows that, with increasing parameter of age, its relief becomes smoother and the number of local minima (network attractors) decreases. As a result, the network gets less frequently stuck in the nearest local minima of the Lyapunov function and reaches a global minimum corresponding to the most effective solution of the cognitive task. It is reasonable to assume that similar changes really occur in the aging brain. Phenomenologically, these changes can be manifested as emergence in aged people of a cognitive quality such as wisdom i.e. ability to find optimal decisions in difficult controversial situations, to distract from secondary aspects and to see the problem as a whole.
-
Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Nakagawa, Seishu; Makoto Miyauchi, Carlos; Sassa, Yuko; Kawashima, Ryuta
2017-05-03
Working memory training (WMT) induces changes in cognitive function and various neurological systems. Here, we investigated changes in recently developed resting state functional magnetic resonance imaging measures of global information processing [degree of the cortical hub, which may have a central role in information integration in the brain, degree centrality (DC)], the magnitude of intrinsic brain activity [fractional amplitude of low frequency fluctuation (fALFF)], and local connectivity (regional homogeneity) in young adults, who either underwent WMT or received no intervention for 4 weeks. Compared with no intervention, WMT increased DC in the anatomical cluster, including anterior cingulate cortex (ACC), to the medial prefrontal cortex (mPFC). Furthermore, WMT increased fALFF in the anatomical cluster including the right dorsolateral prefrontal cortex (DLPFC), frontopolar area and mPFC. WMT increased regional homogeneity in the anatomical cluster that spread from the precuneus to posterior cingulate cortex and posterior parietal cortex. These results suggest WMT-induced plasticity in spontaneous brain activity and global and local information processing in areas of the major networks of the brain during rest.
-
Kim, Dae-Eun; Shin, Jung-Hyun; Kim, Young-Hoon; Eom, Tae-Hoon; Kim, Sung-Hun; Kim, Jung-Min
2016-01-01
Acute confusional migraine (ACM) shows typical electroencephalography (EEG) patterns of diffuse delta slowing and frontal intermittent rhythmic delta activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns suggest neuronal dysfunction in specific brain areas. We performed source localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a patient with ACM during the acute stage. A second EEG was obtained after recovery from ACM. To identify source localization of IRDA, statistical non-parametric mapping using standardized low-resolution brain electromagnetic tomography was performed for the delta frequency band comparisons between ACM attack and non-attack periods. A difference in the current density maximum was found in the dorsal anterior cingulated cortex (ACC). The significant differences were widely distributed over the frontal, parietal, temporal and limbic lobe, paracentral lobule and insula and were predominant in the left hemisphere. Dorsal ACC dysfunction was demonstrated for the first time in a patient with ACM in this source localization analysis of IRDA. The ACC plays an important role in the frontal attentional control system and acute confusion. This dysfunction of the dorsal ACC might represent an important ACM pathophysiology.
-
Berman, Brian D; Horovitz, Silvina G; Hallett, Mark
2013-01-01
The capacity for subjects to learn to volitionally control localized brain activity using neurofeedback is actively being investigated. We aimed to investigate the ability of healthy volunteers to quickly learn to use visual feedback during real-time functional MRI (rtfMRI) to modulate brain activity within their anterior right insular cortex (RIC) localized during a blink suppression task, an approach of possible interest in the use of rtfMRI to reduce urges. The RIC region of interest (RIC-ROI) was functionally localized using a blink suppression task, and blood-oxygen level dependent (BOLD) signal changes within RIC-ROI used to create a constantly updating display fed back to the subject in the scanner. Subjects were instructed to use emotional imagery to try and increase activity within RIC-ROI during four feedback training runs (FB1-FB4). A "control" run (CNTRL) before training and a "transfer" run (XSFR) after training were performed without feedback to assess for baseline abilities and learning effects. Fourteen participants completed all neurofeedback training runs. At the group-level, increased BOLD activity was seen in the anterior RIC during all the FB runs, but a significant increase in the functionally defined RIC-ROI was only attained during FB2. In atlas-defined insular cortex ROIs, significant increases were seen bilaterally during the CNTRL, FB1, FB2, and FB4 runs. Increased activity within the insular cortices did not show lateralization. Training did, however, result in a significant increase in functional connectivity between the RIC-ROI and the medial frontal gyrus when comparing FB4 to FB1. Since neurofeedback training did not lead to an increase in BOLD signal across all feedback runs, we suggest that learning to control one's brain activity in this fashion may require longer or repeated rtfMRI training sessions.
-
A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke
Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.
2015-01-01
The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ≤3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann’s area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of –0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum – but not cortex – was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) μL stroke; 37,819 (9,169) μL control]. When individual regions were examined separately, reduced brain activation volume reached statistical significance in BA6 [p = 0.04; 4,350 (2,347) μL stroke; 6,938 (3,134) μL control] and cerebellum [p = 0.001; 4,591 (1,757) μL stroke; 8,381 (2,835) μL control]. Regardless of whether activated regions were examined together or separately, there were no significant between-group differences in brain activation intensity [p = 0.17; 1.30 (0.25)% stroke; 1.16 (0.20)% control]. Reduced volume in the stroke group was not observed during lower limb tapping and could not be fully attributed to differences in head motion or movement rate. There was a tendency for pedaling-related brain activation volume to increase with increasing work performed by the paretic limb during pedaling (p = 0.08, r = 0.525). Hence, the results of this study provide two original and important contributions. First, we demonstrated that pedaling can be used with fMRI to examine brain activation associated with lower limb movement in people with stroke. Unlike previous lower limb movements examined with fMRI, pedaling involves continuous, reciprocal, multijoint movement of both limbs. In this respect, pedaling has many characteristics of functional lower limb movements, such as walking. Thus, the importance of our contribution lies in the establishment of a novel paradigm that can be used to understand how the brain adapts to stroke to produce functional lower limb movements. Second, preliminary observations suggest that brain activation volume is reduced during pedaling post-stroke. Reduced brain activation volume may be due to anatomic, physiology, and/or behavioral differences between groups, but methodological issues cannot be excluded. Importantly, brain action volume post-stroke was both task-dependent and mutable, which suggests that it could be modified through rehabilitation. Future work will explore these possibilities. PMID:26089789
-
Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials.
Houston, Brady; Blumenfeld, Zack; Quinn, Emma; Bronte-Stewart, Helen; Chizeck, Howard
2015-01-01
Current deep brain stimulation paradigms deliver continuous stimulation to deep brain structures to ameliorate the symptoms of Parkinson's disease. This continuous stimulation has undesirable side effects and decreases the lifespan of the unit's battery, necessitating earlier replacement. A closed-loop deep brain stimulator that uses brain signals to determine when to deliver stimulation based on the occurrence of symptoms could potentially address these drawbacks of current technology. Attempts to detect Parkinsonian tremor using brain signals recorded during the implantation procedure have been successful. However, the ability of these methods to accurately detect tremor over extended periods of time is unknown. Here we use local field potentials recorded during a deep brain stimulation clinical follow-up visit 1 month after initial programming to build a tremor detection algorithm and use this algorithm to detect tremor in subsequent visits up to 8 months later. Using this method, we detected the occurrence of tremor with accuracies between 68-93%. These results demonstrate the potential of tremor detection methods for efficacious closed-loop deep brain stimulation over extended periods of time.
-
Chae, Younbyoung; Lee, In-Seon; Jung, Won-Mo; Chang, Dong-Seon; Napadow, Vitaly; Lee, Hyejung; Park, Hi-Joon; Wallraven, Christian
2014-01-01
Acupuncture stimulation increases local blood flow around the site of stimulation and induces signal changes in brain regions related to the body matrix. The rubber hand illusion (RHI) is an experimental paradigm that manipulates important aspects of bodily self-awareness. The present study aimed to investigate how modifications of body ownership using the RHI affect local blood flow and cerebral responses during acupuncture needle stimulation. During the RHI, acupuncture needle stimulation was applied to the real left hand while measuring blood microcirculation with a LASER Doppler imager (Experiment 1, N = 28) and concurrent brain signal changes using functional magnetic resonance imaging (fMRI; Experiment 2, N = 17). When the body ownership of participants was altered by the RHI, acupuncture stimulation resulted in a significantly lower increase in local blood flow (Experiment 1), and significantly less brain activation was detected in the right insula (Experiment 2). This study found changes in both local blood flow and brain responses during acupuncture needle stimulation following modification of body ownership. These findings suggest that physiological responses during acupuncture stimulation can be influenced by the modification of body ownership. PMID:25285620
-
Detecting activity-evoked pH changes in human brain
Magnotta, Vincent A.; Heo, Hye-Young; Dlouhy, Brian J.; Dahdaleh, Nader S.; Follmer, Robin L.; Thedens, Daniel R.; Welsh, Michael J.; Wemmie, John A.
2012-01-01
Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T1 relaxation in the rotating frame (T1ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T1ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T1ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms. PMID:22566645
-
Xie, Jianwen; Douglas, Pamela K; Wu, Ying Nian; Brody, Arthur L; Anderson, Ariana E
2017-04-15
Brain networks in fMRI are typically identified using spatial independent component analysis (ICA), yet other mathematical constraints provide alternate biologically-plausible frameworks for generating brain networks. Non-negative matrix factorization (NMF) would suppress negative BOLD signal by enforcing positivity. Spatial sparse coding algorithms (L1 Regularized Learning and K-SVD) would impose local specialization and a discouragement of multitasking, where the total observed activity in a single voxel originates from a restricted number of possible brain networks. The assumptions of independence, positivity, and sparsity to encode task-related brain networks are compared; the resulting brain networks within scan for different constraints are used as basis functions to encode observed functional activity. These encodings are then decoded using machine learning, by using the time series weights to predict within scan whether a subject is viewing a video, listening to an audio cue, or at rest, in 304 fMRI scans from 51 subjects. The sparse coding algorithm of L1 Regularized Learning outperformed 4 variations of ICA (p<0.001) for predicting the task being performed within each scan using artifact-cleaned components. The NMF algorithms, which suppressed negative BOLD signal, had the poorest accuracy compared to the ICA and sparse coding algorithms. Holding constant the effect of the extraction algorithm, encodings using sparser spatial networks (containing more zero-valued voxels) had higher classification accuracy (p<0.001). Lower classification accuracy occurred when the extracted spatial maps contained more CSF regions (p<0.001). The success of sparse coding algorithms suggests that algorithms which enforce sparsity, discourage multitasking, and promote local specialization may capture better the underlying source processes than those which allow inexhaustible local processes such as ICA. Negative BOLD signal may capture task-related activations. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review.
Pascual-Marqui, R D; Esslen, M; Kochi, K; Lehmann, D
2002-01-01
This paper reviews several recent publications that have successfully used the functional brain imaging method known as LORETA. Emphasis is placed on the electrophysiological and neuroanatomical basis of the method, on the localization properties of the method, and on the validation of the method in real experimental human data. Papers that criticize LORETA are briefly discussed. LORETA publications in the 1994-1997 period based localization inference on images of raw electric neuronal activity. In 1998, a series of papers appeared that based localization inference on the statistical parametric mapping methodology applied to high-time resolution LORETA images. Starting in 1999, quantitative neuroanatomy was added to the methodology, based on the digitized Talairach atlas provided by the Brain Imaging Centre, Montreal Neurological Institute. The combination of these methodological developments has placed LORETA at a level that compares favorably to the more classical functional imaging methods, such as PET and fMRI.
-
Cornil, C A; Dalla, C; Papadopoulou-Daifoti, Z; Baillien, M; Dejace, C; Ball, G F; Balthazart, J
2005-09-01
In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior.
-
Viral Immunotherapy to Eradicate Subclinical Brain Metastases
2014-05-01
host innate and adaptive immune cells in metastases and normal tissues i. Months 6-21 ii. Basse Brain tissue with D2F2/E2 tumors from animals...and viral antigens which could activate memory T- cells in the draining lymphoid organs. Time course studies showed that virus infection produced a 2.6... lymphoid tissues. III. ACTIVATED NK CELLS LOCALIZE EFFICIENTLY AT TUMOR SITES The densities of NK cells found in well-established tumors in most
-
Amidi, Ali; Hosseini, S M Hadi; Leemans, Alexander; Kesler, Shelli R; Agerbæk, Mads; Wu, Lisa M; Zachariae, Robert
2017-12-01
Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning. Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up. At follow-up, 22 participants had received cisplatin-based chemotherapy (CT) while 42 were in active surveillance (S). Brain structural networks were constructed for each participant, and network properties were investigated using graph theory and longitudinally compared across groups. Cognitive functioning was evaluated using standardized neuropsychological tests. All statistical tests were two-sided. Compared with the S group, the CT group demonstrated altered global and local brain network properties from baseline to follow-up as evidenced by decreases in important brain network properties such as small-worldness (P = .04), network clustering (P = .04), and local efficiency (P = .02). In the CT group, poorer overall cognitive performance was associated with decreased small-worldness (r = -0.46, P = .04) and local efficiency (r = -0.51, P = .02), and verbal fluency was associated with decreased local efficiency (r = -0.55, P = .008). Brain structural networks may be disrupted following treatment with cisplatin-based chemotherapy. Impaired brain networks may underlie poorer performance over time on both specific and nonspecific cognitive functions in patients undergoing chemotherapy. To the best of our knowledge, this is the first study to longitudinally investigate changes in structural brain networks in a cancer population, providing novel insights regarding the neurobiological mechanisms of cancer-related cognitive impairment.
-
Using human extra-cortical local field potentials to control a switch
NASA Astrophysics Data System (ADS)
Kennedy, Philip; Andreasen, Dinal; Ehirim, Princewill; King, Brandon; Kirby, Todd; Mao, Hui; Moore, Melody
2004-06-01
Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate. Financial disclosure. Authors PK and DA may derive some financial gain from the sale of this device. A patent has been applied under US and international law: 10/675,703.
-
Regional homogeneity of the resting-state brain activity correlates with individual intelligence.
Wang, Leiqiong; Song, Ming; Jiang, Tianzi; Zhang, Yunting; Yu, Chunshui
2011-01-25
Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
-
Michalec, Katarzyna; Mysiorek, Caroline; Kuntz, Mélanie; Bérézowski, Vincent; Szczepankiewicz, Andrzej A; Wilczyński, Grzegorz M; Cecchelli, Roméo; Nałęcz, Katarzyna A
2014-07-15
Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood-brain barrier (BBB). Expression and presence of two carnitine transporters - organic cation/carnitine transporter (OCTN2) and amino acid transporter B(0,+) (ATB(0,+)) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB(0,+) sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB(0,+) can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB(0,+) luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB(0,+) was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB(0,+) present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB(0,+) inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Brain-Mind Operational Architectonics Imaging: Technical and Methodological Aspects
Fingelkurts, Andrew A; Fingelkurts, Alexander A
2008-01-01
This review paper deals with methodological and technical foundations of the Operational Architectonics framework of brain and mind functioning. This theory provides a framework for mapping and understanding important aspects of the brain mechanisms that constitute perception, cognition, and eventually consciousness. The methods utilized within Operational Architectonics framework allow analyzing with an incredible detail the operational behavior of local neuronal assemblies and their joint activity in the form of unified and metastable operational modules, which constitute the whole hierarchy of brain operations, operations of cognition and phenomenal consciousness. PMID:19526071
-
Integrating EEG and fMRI in epilepsy.
Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria
2011-02-14
Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear interictal spikes. Copyright © 2010 Elsevier Inc. All rights reserved.
-
Neuronal avalanches and coherence potentials
NASA Astrophysics Data System (ADS)
Plenz, D.
2012-05-01
The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.
-
The inverse problem in electroencephalography using the bidomain model of electrical activity.
Lopez Rincon, Alejandro; Shimoda, Shingo
2016-12-01
Acquiring information about the distribution of electrical sources in the brain from electroencephalography (EEG) data remains a significant challenge. An accurate solution would provide an understanding of the inner mechanisms of the electrical activity in the brain and information about damaged tissue. In this paper, we present a methodology for reconstructing brain electrical activity from EEG data by using the bidomain formulation. The bidomain model considers continuous active neural tissue coupled with a nonlinear cell model. Using this technique, we aim to find the brain sources that give rise to the scalp potential recorded by EEG measurements taking into account a non-static reconstruction. We simulate electrical sources in the brain volume and compare the reconstruction to the minimum norm estimates (MNEs) and low resolution electrical tomography (LORETA) results. Then, with the EEG dataset from the EEG Motor Movement/Imagery Database of the Physiobank, we identify the reaction to visual stimuli by calculating the time between stimulus presentation and the spike in electrical activity. Finally, we compare the activation in the brain with the registered activation using the LinkRbrain platform. Our methodology shows an improved reconstruction of the electrical activity and source localization in comparison with MNE and LORETA. For the Motor Movement/Imagery Database, the reconstruction is consistent with the expected position and time delay generated by the stimuli. Thus, this methodology is a suitable option for continuously reconstructing brain potentials. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.
-
Gambino, Giuditta; Allegra, Mario; Sardo, Pierangelo; Attanzio, Alessandro; Tesoriere, Luisa; Livrea, Maria A.; Ferraro, Giuseppe; Carletti, Fabio
2018-01-01
Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could modulate neuronal function with a relapse on complex cognitive brain process and related neurodegenerative conditions. PMID:29867444
-
Annexin A1 Complex Mediates Oxytocin Vesicle Transport
Makani, Vishruti; Sultana, Rukhsana; Sie, Khin Sander; Orjiako, Doris; Tatangelo, Marco; Dowling, Abigail; Cai, Jian; Pierce, William; Butterfield, D. Allan; Hill, Jennifer; Park, Joshua
2013-01-01
Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body. PMID:24118254
-
Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E
2018-01-01
Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.
-
Fueling and imaging brain activation
Dienel, Gerald A
2012-01-01
Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861
-
'What' and 'where' in the human brain.
Ungerleider, L G; Haxby, J V
1994-04-01
Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms.
-
Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel
2017-03-01
Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Butz, Markus; Steenbuck, Ines D; van Ooyen, Arjen
2014-01-01
After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity-a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.
-
The devil is in the detail: brain dynamics in preparation for a global-local task.
Leaver, Echo E; Low, Kathy A; DiVacri, Assunta; Merla, Arcangelo; Fabiani, Monica; Gratton, Gabriele
2015-08-01
When analyzing visual scenes, it is sometimes important to determine the relevant "grain" size. Attention control mechanisms may help direct our processing to the intended grain size. Here we used the event-related optical signal, a method possessing high temporal and spatial resolution, to examine the involvement of brain structures within the dorsal attention network (DAN) and the visual processing network (VPN) in preparation for the appropriate level of analysis. Behavioral data indicate that the small features of a hierarchical stimulus (local condition) are more difficult to process than the large features (global condition). Consistent with this finding, cues predicting a local trial were associated with greater DAN activation. This activity was bilateral but more pronounced in the left hemisphere, where it showed a frontal-to-parietal progression over time. Furthermore, the amount of DAN activation, especially in the left hemisphere and in parietal regions, was predictive of subsequent performance. Although local cues elicited left-lateralized DAN activity, no preponderantly right activity was observed for global cues; however, the data indicated an interaction between level of analysis (local vs. global) and hemisphere in VPN. They further showed that local processing involves structures in the ventral VPN, whereas global processing involves structures in the dorsal VPN. These results indicate that in our study preparation for analyzing different size features is an asymmetric process, in which greater preparation is required to focus on small rather than large features, perhaps because of their lesser salience. This preparation involves the same DAN used for other attention control operations.
-
Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation
Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.
2016-01-01
Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709
-
Sarasso, S; Santhanam, P; Määtta, S; Poryazova, R; Ferrarelli, F; Tononi, G; Small, S L
2010-09-01
Stroke is associated with long-term functional deficits. Behavioral interventions are often effective in promoting functional recovery and plastic changes. Recent studies in normal subjects have shown that sleep, and particularly slow wave activity (SWA), is tied to local brain plasticity and may be used as a sensitive marker of local cortical reorganization after stroke. In a pilot study, we assessed the local changes induced by a single exposure to a therapeutic session of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects), a behavioral therapy used for recovery in patients with post-stroke aphasia. In addition, we measured brain activity changes with functional magnetic resonance imaging (fMRI) in a language observation task before, during and after the full IMITATE rehabilitative program. Speech production improved both after a single exposure and the full therapy program as measured by the Western Aphasia Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization in functionally-connected, speech-relevant areas in the left hemisphere. These preliminary results suggest that sleep hd-EEGs, and the topographical analysis of SWA parameters, are well suited to investigate brain plastic changes underpinning functional recovery in neurological disorders.
-
Effect of whole brain radiation on local cerebral glucose utilization in the rat.
d'Avella, D; Cicciarello, R; Albiero, F; Mesiti, M; Gagliardi, M E; Russi, E; d'Aquino, A; Princi, P; d'Aquino, S
1991-04-01
We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week; total dose, 4000 cGy). Metabolic experiments were made 2 to 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased after irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, the brain areas with the highest basal metabolic rates showed the greatest percentage of decrease in glucose utilization. The concept that radiation suppresses glucose utilization before any morphological change takes place in the cell structures was the basis of this study. Metabolic alterations after irradiation may explain the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. These studies have applications to observations made with the [18F]-fluorodeoxyglucose method in conjunction with positron emission tomographic scans in patients receiving radiation therapy for intracranial malignancies. The data reported here also have potential clinical implications for the evaluation of a risk/benefit ratio for radiotherapy in patients with benign neurosurgical diseases or children undergoing prophylactic treatment of the central nervous system.
-
Akdeniz, Gülsüm
2016-01-01
Background: Few studies have been conducted that have compared electrical source localization (ESL) results obtained by analyzing ictal patterns in scalp electroencephalogram (EEG) with the brain areas that are found to be responsible for seizures using other brain imaging techniques. Additionally, adequate studies have not been performed to confirm the accuracy of ESL methods. Materials and Methods: In this study, ESL was conducted using LORETA (Low Resolution Brain Electromagnetic Tomography) in 9 patients with lesions apparent on magnetic resonance imaging (MRI) and in 6 patients who did not exhibit lesions on their MRIs. EEGs of patients who underwent surgery for epilepsy and had follow-ups for at least 1 year after operations were analyzed for ictal spike, rhythmic, paroxysmal fast, and obscured EEG activities. Epileptogenic zones identified in postoperative MRIs were then compared with localizations obtained by LORETA model we employed. Results: We found that brain areas determined via ESL were in concordance with resected brain areas for 13 of the 15 patients evaluated, and those 13 patients were post-operatively determined as being seizure-free. Conclusion: ESL, which is a noninvasive technique, may contribute to the correct delineation of epileptogenic zones in patients who will eventually undergo surgery to treat epilepsy, (regardless of neuroimaging status). Moreover, ESL may aid in deciding on the number and localization of intracranial electrodes to be used in patients who are candidates for invasive recording. PMID:27011626
-
Akdeniz, Gülsüm
2016-01-01
Few studies have been conducted that have compared electrical source localization (ESL) results obtained by analyzing ictal patterns in scalp electroencephalogram (EEG) with the brain areas that are found to be responsible for seizures using other brain imaging techniques. Additionally, adequate studies have not been performed to confirm the accuracy of ESL methods. In this study, ESL was conducted using LORETA (Low Resolution Brain Electromagnetic Tomography) in 9 patients with lesions apparent on magnetic resonance imaging (MRI) and in 6 patients who did not exhibit lesions on their MRIs. EEGs of patients who underwent surgery for epilepsy and had follow-ups for at least 1 year after operations were analyzed for ictal spike, rhythmic, paroxysmal fast, and obscured EEG activities. Epileptogenic zones identified in postoperative MRIs were then compared with localizations obtained by LORETA model we employed. We found that brain areas determined via ESL were in concordance with resected brain areas for 13 of the 15 patients evaluated, and those 13 patients were post-operatively determined as being seizure-free. ESL, which is a noninvasive technique, may contribute to the correct delineation of epileptogenic zones in patients who will eventually undergo surgery to treat epilepsy, (regardless of neuroimaging status). Moreover, ESL may aid in deciding on the number and localization of intracranial electrodes to be used in patients who are candidates for invasive recording.
-
Electromagnetic Evidence of Altered Visual Processing in Autism
ERIC Educational Resources Information Center
Neumann, Nicola; Dubischar-Krivec, Anna M.; Poustka, Fritz; Birbaumer, Niels; Bolte, Sven; Braun, Christoph
2011-01-01
Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli…
-
NASA Astrophysics Data System (ADS)
Chen, Yuanxin; Mancuso, James; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.
2013-03-01
Neurovascular dysfunction in many neurodegenerative diseases, such as Alzheimer's disease (AD), reduces blood flow to affected brain areas and causes neuronal dysfunction and loss. A new optical imaging technique is developed to activate astrocytes in live animal models in order to investigate the increase of local cerebral blood flow as a potential therapeutic strategy for AD. The technique uses fluorescent labeling of vasculature and astrocytes coupled with intravital 2-photon microscopy to visualize the astrocyte-vasculature interactions in live animals. Using femtosecond laser stimulation, calcium uncaging is applied to specifically target and activate astrocytes in vivo with high spatial and temporal resolutions. Intravital 2-photon microscopy imaging was employed to demonstrate that single endfoot optical activation around an arteriole induced a 25% increase in arteriole diameter, which in turn increased cerebral local blood flow in down-stream capillaries. This quantitative result indicates the potential of using optical activation of astrocytes in afflicted brain areas of neurodegeneration to restore normal neurovascular functions.
-
van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A
2016-01-01
Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated. Seven weeks after kainic acid-induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity. (Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin-treated rats compared to vehicle-treated rats. In vitro studies showed that rapamycin could attenuate TNFα-induced endothelial barrier breakdown. These data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
-
Matsumoto, Atsushi; Kakigi, Ryusuke
2014-01-01
Recent neuroimaging experiments have revealed that subliminal priming of a target stimulus leads to the reduction of neural activity in specific regions concerned with processing the target. Such findings lead to questions about the degree to which the subliminal priming effect is based only on decreased activity in specific local brain regions, as opposed to the influence of neural mechanisms that regulate communication between brain regions. To address this question, this study recorded EEG during performance of a subliminal semantic priming task. We adopted an information-based approach that used independent component analysis and multivariate autoregressive modeling. Results indicated that subliminal semantic priming caused significant modulation of alpha band activity in the left inferior frontal cortex and modulation of gamma band activity in the left inferior temporal regions. The multivariate autoregressive approach confirmed significant increases in information flow from the inferior frontal cortex to inferior temporal regions in the early time window that was induced by subliminal priming. In the later time window, significant enhancement of bidirectional causal flow between these two regions underlying subliminal priming was observed. Results suggest that unconscious processing of words influences not only local activity of individual brain regions but also the dynamics of neural communication between those regions.
-
Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes
NASA Astrophysics Data System (ADS)
Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.
2015-12-01
Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.
-
Liu, Chang; Xue, Zhimin; Palaniyappan, Lena; Zhou, Li; Liu, Haihong; Qi, Chang; Wu, Guowei; Mwansisya, Tumbwene E; Tao, Haojuan; Chen, Xudong; Huang, Xiaojun; Liu, Zhening; Pu, Weidan
2016-03-01
Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Local Network-Level Integration Mediates Effects of Transcranial Alternating Current Stimulation.
Fuscà, Marco; Ruhnau, Philipp; Neuling, Toralf; Weisz, Nathan
2018-05-01
Transcranial alternating current stimulation (tACS) has been proposed as a tool to draw causal inferences on the role of oscillatory activity in cognitive functioning and has the potential to induce long-term changes in cerebral networks. However, effectiveness of tACS underlies high variability and dependencies, which, as previous modeling works have suggested, may be mediated by local and network-level brain states. We used magnetoencephalography to record brain activity from 17 healthy participants at rest as they kept their eyes open (EO) or eyes closed (EC) while being stimulated with sham, weak, or strong alpha-tACS using a montage commonly assumed to target occipital areas. We reconstructed the activity of sources in all stimulation conditions by means of beamforming. The analysis of resting-state brain activity revealed an interaction of the external stimulation with the endogenous alpha power increase from EO to EC. This interaction was localized to the posterior cingulate, a region remote from occipital cortex. This suggests state-dependent (EO vs. EC) long-range effects of tACS. In a follow-up analysis of this online-tACS effect, we find evidence that this state-dependency effect is mediated by functional network changes: connection strength from the precuneus was significantly correlated with the state-dependency effect in the posterior cingulate during tACS. No analogous correlation could be found for alpha power modulations in occipital cortex. Altogether, this is the first strong evidence to illustrate how functional network architectures can shape tACS effects.
-
Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events.
Ramirez-Villegas, Juan F; Logothetis, Nikos K; Besserve, Michel
2015-11-17
Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.
-
Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events
Ramirez-Villegas, Juan F.; Logothetis, Nikos K.; Besserve, Michel
2015-01-01
Sharp-wave–ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R–triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions. PMID:26540729
-
Leaping from brain to mind: a critique of mirror neuron explanations of countertransference.
Vivona, Jeanine M
2009-06-01
In the current vigorous debate over the value of neuroscience to psychoanalysis, the epistemological status of the links between the data of brain research and the constructs of interest to psychoanalysts has rarely been examined. An inspection of recent discussions of mirror neuron research, particularly regarding countertransference, reveals gaps between psychoanalytic processes and the available brain activation data, and allows the evaluation of evidence for three implicit assumptions frequently made to bridge these gaps: (1) there is a straightforward correspondence between observed brain activity and mental activity; (2) similarity of localized brain activity across individuals signifies a shared interpersonal experience; (3) an automatic brain mechanism enables direct interpersonal sharing of experiences in the absence of inference and language. Examination of mirror neuron research findings reveals that these assumptions are either untested or questionable. Moreover, within neuroscience there are competing interpretations of mirror neuron findings, with diverse implications for psychoanalysis. The present state of mirror neuron research may offer us new hypotheses or metaphors, but does not provide empirical validation of the proposed models. More generally, as we attempt to learn from research findings generated outside psychoanalysis, we must strive to think scientifically, by minding the difference between data and interpretation.
-
Role of local network oscillations in resting-state functional connectivity.
Cabral, Joana; Hugues, Etienne; Sporns, Olaf; Deco, Gustavo
2011-07-01
Spatio-temporally organized low-frequency fluctuations (<0.1 Hz), observed in BOLD fMRI signal during rest, suggest the existence of underlying network dynamics that emerge spontaneously from intrinsic brain processes. Furthermore, significant correlations between distinct anatomical regions-or functional connectivity (FC)-have led to the identification of several widely distributed resting-state networks (RSNs). This slow dynamics seems to be highly structured by anatomical connectivity but the mechanism behind it and its relationship with neural activity, particularly in the gamma frequency range, remains largely unknown. Indeed, direct measurements of neuronal activity have revealed similar large-scale correlations, particularly in slow power fluctuations of local field potential gamma frequency range oscillations. To address these questions, we investigated neural dynamics in a large-scale model of the human brain's neural activity. A key ingredient of the model was a structural brain network defined by empirically derived long-range brain connectivity together with the corresponding conduction delays. A neural population, assumed to spontaneously oscillate in the gamma frequency range, was placed at each network node. When these oscillatory units are integrated in the network, they behave as weakly coupled oscillators. The time-delayed interaction between nodes is described by the Kuramoto model of phase oscillators, a biologically-based model of coupled oscillatory systems. For a realistic setting of axonal conduction speed, we show that time-delayed network interaction leads to the emergence of slow neural activity fluctuations, whose patterns correlate significantly with the empirically measured FC. The best agreement of the simulated FC with the empirically measured FC is found for a set of parameters where subsets of nodes tend to synchronize although the network is not globally synchronized. Inside such clusters, the simulated BOLD signal between nodes is found to be correlated, instantiating the empirically observed RSNs. Between clusters, patterns of positive and negative correlations are observed, as described in experimental studies. These results are found to be robust with respect to a biologically plausible range of model parameters. In conclusion, our model suggests how resting-state neural activity can originate from the interplay between the local neural dynamics and the large-scale structure of the brain. Copyright © 2011 Elsevier Inc. All rights reserved.
-
A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface
Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf
2016-01-01
All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264
-
Spatio-Temporal Brain Mapping of Motion-Onset VEPs Combined with fMRI and Retinotopic Maps
Pitzalis, Sabrina; Strappini, Francesca; De Gasperis, Marco; Bultrini, Alessandro; Di Russo, Francesco
2012-01-01
Neuroimaging studies have identified several motion-sensitive visual areas in the human brain, but the time course of their activation cannot be measured with these techniques. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic brain mapping) to determine the spatio-temporal profile of motion-onset visual evoked potentials for slow and fast motion stimuli and to localize its neural generators. We found that cortical activity initiates in the primary visual area (V1) for slow stimuli, peaking 100 ms after the onset of motion. Subsequently, activity in the mid-temporal motion-sensitive areas, MT+, peaked at 120 ms, followed by peaks in activity in the more dorsal area, V3A, at 160 ms and the lateral occipital complex at 180 ms. Approximately 250 ms after stimulus onset, activity fast motion stimuli was predominant in area V6 along the parieto-occipital sulcus. Finally, at 350 ms (100 ms after the motion offset) brain activity was visible again in area V1. For fast motion stimuli, the spatio-temporal brain pattern was similar, except that the first activity was detected at 70 ms in area MT+. Comparing functional magnetic resonance data for slow vs. fast motion, we found signs of slow-fast motion stimulus topography along the posterior brain in at least three cortical regions (MT+, V3A and LOR). PMID:22558222
-
Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W
2016-01-01
Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots." At these NE hotspots, local glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. In contrast, arousal-induced LC activity inhibits less active representations via two mechanisms: 1) Where there are hotspots, lateral inhibition is amplified; 2) Where no hotspots emerge, NE levels are only high enough to activate low-threshold inhibitory adrenoreceptors. Thus, LC activation promotes a few hotspots of excitation in the context of widespread suppression, enhancing high priority representations while suppressing the rest. Hotspots also help synchronize oscillations across neural ensembles transmitting high-priority information. Furthermore, brain structures that detect stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during, or after encoding enhances synaptic plasticity at NE hotspots, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms promote selective attention and memory under arousal. GANE not only reconciles apparently contradictory findings in the emotion-cognition literature but also extends previous influential theories of LC neuromodulation by proposing specific mechanisms for how LC-NE activity increases neural gain.
-
Nicotine increases brain functional network efficiency.
Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R
2012-10-15
Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.
-
Nicotine Increases Brain Functional Network Efficiency
Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Laura F.; Tregellas, Jason R.
2012-01-01
Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. PMID:22796985
-
Functional Geometry Alignment and Localization of Brain Areas.
Langs, Georg; Golland, Polina; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J
2010-01-01
Matching functional brain regions across individuals is a challenging task, largely due to the variability in their location and extent. It is particularly difficult, but highly relevant, for patients with pathologies such as brain tumors, which can cause substantial reorganization of functional systems. In such cases spatial registration based on anatomical data is only of limited value if the goal is to establish correspondences of functional areas among different individuals, or to localize potentially displaced active regions. Rather than rely on spatial alignment, we propose to perform registration in an alternative space whose geometry is governed by the functional interaction patterns in the brain. We first embed each brain into a functional map that reflects connectivity patterns during a fMRI experiment. The resulting functional maps are then registered, and the obtained correspondences are propagated back to the two brains. In application to a language fMRI experiment, our preliminary results suggest that the proposed method yields improved functional correspondences across subjects. This advantage is pronounced for subjects with tumors that affect the language areas and thus cause spatial reorganization of the functional regions.
-
Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.
Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D
2015-01-01
Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.
-
Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding
Pedersen, Mangor; Omidvarnia, Amir H.; Walz, Jennifer M.; Jackson, Graeme D.
2015-01-01
Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications. PMID:26110111
-
Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.
Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng
2015-01-01
The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.
-
Detecting large-scale networks in the human brain using high-density electroencephalography.
Liu, Quanying; Farahibozorg, Seyedehrezvan; Porcaro, Camillo; Wenderoth, Nicole; Mantini, Dante
2017-09-01
High-density electroencephalography (hdEEG) is an emerging brain imaging technique that can be used to investigate fast dynamics of electrical activity in the healthy and the diseased human brain. Its applications are however currently limited by a number of methodological issues, among which the difficulty in obtaining accurate source localizations. In particular, these issues have so far prevented EEG studies from reporting brain networks similar to those previously detected by functional magnetic resonance imaging (fMRI). Here, we report for the first time a robust detection of brain networks from resting state (256-channel) hdEEG recordings. Specifically, we obtained 14 networks previously described in fMRI studies by means of realistic 12-layer head models and exact low-resolution brain electromagnetic tomography (eLORETA) source localization, together with independent component analysis (ICA) for functional connectivity analysis. Our analyses revealed three important methodological aspects. First, brain network reconstruction can be improved by performing source localization using the gray matter as source space, instead of the whole brain. Second, conducting EEG connectivity analyses in individual space rather than on concatenated datasets may be preferable, as it permits to incorporate realistic information on head modeling and electrode positioning. Third, the use of a wide frequency band leads to an unbiased and generally accurate reconstruction of several network maps, whereas filtering data in a narrow frequency band may enhance the detection of specific networks and penalize that of others. We hope that our methodological work will contribute to rise of hdEEG as a powerful tool for brain research. Hum Brain Mapp 38:4631-4643, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
-
Sekihara, K; Poeppel, D; Marantz, A; Koizumi, H; Miyashita, Y
1997-09-01
This paper proposes a method of localizing multiple current dipoles from spatio-temporal biomagnetic data. The method is based on the multiple signal classification (MUSIC) algorithm and is tolerant of the influence of background brain activity. In this method, the noise covariance matrix is estimated using a portion of the data that contains noise, but does not contain any signal information. Then, a modified noise subspace projector is formed using the generalized eigenvectors of the noise and measured-data covariance matrices. The MUSIC localizer is calculated using this noise subspace projector and the noise covariance matrix. The results from a computer simulation have verified the effectiveness of the method. The method was then applied to source estimation for auditory-evoked fields elicited by syllable speech sounds. The results strongly suggest the method's effectiveness in removing the influence of background activity.
-
Xie, Kun; Fox, Grace E.; Liu, Jun; Tsien, Joe Z.
2016-01-01
The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse’s small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages – namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli – such as an earthquake and fear-inducing foot-shock – trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID:27378865
-
Rose, K; Allan, A; Gauldie, S; Stapleton, G; Dobbie, L; Dott, K; Martin, C; Wang, L; Hedlund, E; Seckl, J R; Gustafsson, J A; Lathe, R
2001-06-29
The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and immune function but has no known dedicated receptor; local metabolism may govern its activity. We described a cytochrome P450 expressed in brain and other tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta-hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha-hydroxylation activity are widespread in rat tissues. However, steroids related to DHEA are reported to be modified at positions other than 7alpha, exemplified by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is responsible for these and other activities we disrupted the mouse Cyp7b gene by targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse brain, chromogenic detection of reporter activity was strikingly restricted to the dentate gyrus. Staining did not exactly reproduce the in situ hybridization expression pattern; post-transcriptional control is inferred. Lower level staining was detected in cerebellum, liver, and kidney, and which largely paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic. Mice homozygous for the insertion are viable and superficially normal, but ex vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen, thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol and related substrates was also abolished, as was presumed 6alpha-hydroxylation of A/anediol. These different enzyme activities therefore derive from the Cyp7b gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues.
-
Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F
2017-08-01
Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Itoh, Toru; Sumiyoshi, Tomiki; Higuchi, Yuko; Suzuki, Michio; Kawasaki, Yasuhiro
2011-08-01
We sought to determine if altered electroencephalography (EEG) activities, such as delta band activity, in specific brain regions are associated with psychotic symptoms. Data were obtained from 17 neuroleptic-naive patients with schizophrenia and age- and sex-matched 17 healthy control subjects. Low Resolution Brain Electromagnetic Tomography (LORETA) was used to generate current source density images of delta, theta, alpha, and beta activities. Localization of the difference in EEG activity between the two groups was assessed by voxel-by-voxel non-paired t-test of the LORETA images. Spearman's correlation coefficient was obtained to relate LORETA values of EEG current density in brain regions showing a significant between-group difference and psychopathology scores. Delta band activity, represented by LORETA current density, was greater for patients in the following areas; the left inferior temporal gyrus, right middle frontal gyrus, right superior frontal gyrus, right inferior frontal gyrus, and right parahippocampal gyrus. LORETA values for delta band activity in the above five brain regions were negatively correlated with negative, but not positive symptoms. The results of this study suggest the role for electrophysiological changes in some of the brain regions, e.g. prefrontal cortex, in the manifestation of negative symptoms. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Marra, Kyle; Graham, Brett; Carouso, Samantha; Cox, David
2012-02-01
While the application of local cortical cooling has recently become a focus of neurological research, extended localized deactivation deep within brain structures is still unexplored. Using a wirelessly controlled thermoelectric (Peltier) device and water-based heat sink, we have achieved inactivating temperatures (<20 C) at greater depths (>8 mm) than previously reported. After implanting the device into Long Evans rats' basolateral amygdala (BLA), an inhibitory brain center that controls anxiety and fear, we ran an open field test during which anxiety-driven behavioral tendencies were observed to decrease during cooling, thus confirming the device's effect on behavior. Our device will next be implanted in the rats' temporal association cortex (TeA) and recordings from our signal-tracing multichannel microelectrodes will measure and compare activated and deactivated neuronal activity so as to isolate and study the TeA signals responsible for object recognition. Having already achieved a top performing computational face-recognition system, the lab will utilize this TeA activity data to generalize its computational efforts of face recognition to achieve general object recognition.
-
Walla, P; Hufnagl, B; Lindinger, G; Imhof, H; Deecke, L; Lang, W
2001-03-01
Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance. Copyright 2001 Academic Press.
-
Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W.
2018-01-01
Long Abstract Existing brain-based emotion-cognition theories fail to explain arousal’s ability to both enhance and impair cognitive processing. In the Glutamate Amplifies Noradrenergic Effects (GANE) model outlined in this paper, we propose that arousal-induced norepinephrine (NE) released from the locus coeruleus (LC) biases perception and memory in favor of salient, high priority representations at the expense of lower priority representations. This increase in gain under phasic arousal occurs via synaptic self-regulation of NE based on glutamate levels. When the LC is phasically active, elevated levels of glutamate at the site of prioritized representations increase local NE release, creating “NE hot spots.” At these local hot spots, glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. This excitatory effect contrasts with widespread NE suppression of weaker representations via lateral and auto-inhibitory processes. On a broader scale, hot spots increase oscillatory synchronization across neural ensembles transmitting high priority information. Furthermore, key brain structures that detect or pre-determine stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during or after encoding enhances synaptic plasticity at sites of high glutamate activity, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms increase perceptual and memory selectivity under arousal. Beyond explaining discrepancies in the emotion-cognition literature, GANE reconciles and extends previous influential theories of LC neuromodulation by highlighting how NE can produce such different outcomes in processing based on priority. PMID:26126507
-
Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M
2016-08-01
One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.
-
Integrating Retraction Modeling Into an Atlas-Based Framework for Brain Shift Prediction
Chen, Ishita; Ong, Rowena E.; Simpson, Amber L.; Sun, Kay; Thompson, Reid C.
2015-01-01
In recent work, an atlas-based statistical model for brain shift prediction, which accounts for uncertainty in the intraoperative environment, has been proposed. Previous work reported in the literature using this technique did not account for local deformation caused by surgical retraction. It is challenging to precisely localize the retractor location prior to surgery and the retractor is often moved in the course of the procedure. This paper proposes a technique that involves computing the retractor-induced brain deformation in the operating room through an active model solve and linearly superposing the solution with the precomputed deformation atlas. As a result, the new method takes advantage of the atlas-based framework’s accounting for uncertainties while also incorporating the effects of retraction with minimal intraoperative computing. This new approach was tested using simulation and phantom experiments. The results showed an improvement in average shift correction from 50% (ranging from 14 to 81%) for gravity atlas alone to 80% using the active solve retraction component (ranging from 73 to 85%). This paper presents a novel yet simple way to integrate retraction into the atlas-based brain shift computation framework. PMID:23864146
-
Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury
Pardini, M.; Krueger, F.; Hodgkinson, C.; Raymont, V.; Ferrier, C.; Goldman, D.; Strenziok, M.; Guida, S.
2011-01-01
Objective: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI). Methods: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a). Results: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group. Conclusions: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI. PMID:21422455
-
Litvak, Vladimir; Eusebio, Alexandre; Jha, Ashwani; Oostenveld, Robert; Barnes, Gareth R; Penny, William D; Zrinzo, Ludvic; Hariz, Marwan I; Limousin, Patricia; Friston, Karl J; Brown, Peter
2010-05-01
Insight into how brain structures interact is critical for understanding the principles of functional brain architectures and may lead to better diagnosis and therapy for neuropsychiatric disorders. We recorded, simultaneously, magnetoencephalographic (MEG) signals and subcortical local field potentials (LFP) in a Parkinson's disease (PD) patient with bilateral deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). These recordings offer a unique opportunity to characterize interactions between the subcortical structures and the neocortex. However, high-amplitude artefacts appeared in the MEG. These artefacts originated from the percutaneous extension wire, rather than from the actual DBS electrode and were locked to the heart beat. In this work, we show that MEG beamforming is capable of suppressing these artefacts and quantify the optimal regularization required. We demonstrate how beamforming makes it possible to localize cortical regions whose activity is coherent with the STN-LFP, extract artefact-free virtual electrode time-series from regions of interest and localize cortical areas exhibiting specific task-related power changes. This furnishes results that are consistent with previously reported results using artefact-free MEG data. Our findings demonstrate that physiologically meaningful information can be extracted from heavily contaminated MEG signals and pave the way for further analysis of combined MEG-LFP recordings in DBS patients. 2009 Elsevier Inc. All rights reserved.
-
Electric Field Encephalography as a tool for functional brain research: a modeling study.
Petrov, Yury; Sridhar, Srinivas
2013-01-01
We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2-3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.
-
Local cortical dynamics of burst suppression in the anaesthetized brain.
Lewis, Laura D; Ching, Shinung; Weiner, Veronica S; Peterfreund, Robert A; Eskandar, Emad N; Cash, Sydney S; Brown, Emery N; Purdon, Patrick L
2013-09-01
Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric 'suppressions' lasting seconds or minutes, and high-voltage 'bursts'. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a 'global' state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.
-
Langer, Julia; Gerkau, Niklas J; Derouiche, Amin; Kleinhans, Christian; Moshrefi-Ravasdjani, Behrouz; Fredrich, Michaela; Kafitz, Karl W; Seifert, Gerald; Steinhäuser, Christian; Rose, Christine R
2017-02-01
Perivascular endfeet of astrocytes are highly polarized compartments that ensheath blood vessels and contribute to the blood-brain barrier. They experience calcium transients with neuronal activity, a phenomenon involved in neurovascular coupling. Endfeet also mediate the uptake of glucose from the blood, a process stimulated in active brain regions. Here, we demonstrate in mouse hippocampal tissue slices that endfeet undergo sodium signaling upon stimulation of glutamatergic synaptic activity. Glutamate-induced endfeet sodium transients were diminished by TFB-TBOA, suggesting that they were generated by sodium-dependent glutamate uptake. With local agonist application, they could be restricted to endfeet and immunohistochemical analysis revealed prominent expression of glutamate transporters GLAST and GLT-1 localized towards the neuropil vs. the vascular side of endfeet. Endfeet sodium signals spread at an apparent maximum velocity of ∼120 µm/s and directly propagated from stimulated into neighboring endfeet; this spread was omitted in Cx30/Cx43 double-deficient mice. Sodium transients resulted in elevation of intracellular magnesium, indicating a decrease in intracellular ATP. In summary, our results establish that excitatory synaptic activity and stimulation of glutamate uptake in astrocytes trigger transient sodium increases in perivascular endfeet which rapidly spread through gap junctions into neighboring endfeet and cause a reduction of intracellular ATP. The newly discovered endfeet sodium signaling thereby represents a fast, long-lived and inter-cellularly acting indicator of synaptic activity at the blood-brain barrier, which likely constitutes an important component of neuro-metabolic coupling in the brain. GLIA 2017;65:293-308. © 2016 Wiley Periodicals, Inc.
-
Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation
Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.
2017-01-01
The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947
-
Casanova, Ramon; Hayasaka, Satoru; Saldana, Santiago; Bryan, Nick R.; Demos, Kathryn E.; Desiderio, Lisa; Erickson, Kirk I.; Espeland, Mark A.; Nasrallah, Ilya M.; Wadden, Thomas; Laurienti, Paul J.
2016-01-01
A number of studies have reported that type 2 diabetes mellitus (T2DM) is associated with alterations in resting-state activity and connectivity in the brain. There is also evidence that interventions involving physical activity and weight loss may affect brain functional connectivity. In this study, we examined the effects of nearly 10 years of an intensive lifestyle intervention (ILI), designed to induce and sustain weight loss through lower caloric intake and increased physical activity, on resting-state networks in adults with T2DM. We performed a cross-sectional comparison of global and local characteristics from functional brain networks between individuals who had been randomly assigned to ILI or a control condition of health education and support. Upon examining brain networks from 312 participants (average age: 68.8 for ILI and 67.9 for controls), we found that ILI participants (N=160) had attenuated local efficiency at the network-level compared with controls (N=152). Although there was no group difference in the network-level global efficiency, we found that, among ILI participants, nodal global efficiency was elevated in left fusiform gyrus, right middle frontal gyrus, and pars opercularis of right inferior frontal gyrus. These effects were age-dependent, with more pronounced effects for older participants. Overall these results indicate that the individuals assigned to the ILI had brain networks with less regional and more global connectivity, particularly involving frontal lobes. Such patterns would support greater distributed information processing. Future studies are needed to determine if these differences are associated with age-related compensatory function in the ILI group or worse pathology in the control group. PMID:27685338
-
Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul
2016-01-01
Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto-posterior connectivity even in the absence of behavioral impairment.
-
Lagarrigue, Aurélie; Longcamp, Marieke; Anton, Jean Luc; Nazarian, Bruno; Prévot, Laurent; Velay, Jean-Luc; Cao, Fan; Frenck-Mestre, Cheryl
2017-03-01
We examined the implication of training modality on the cortical representation of Chinese words in adult second language learners of Chinese. In particular, we tested the implication of the neural substrates of writing in a reading task. The brain network sustaining finger writing was defined neuroanatomically based on an independent functional localizer. We examined the brain activations elicited by Chinese words learned via writing vs. pronunciation, and by novel untrained words, within regions of interest (ROIs) defined according to the position of the activation peaks in the localizer, and at the whole brain level. We revealed activations in the reading task that overlapped with several parts of the finger writing network. In addition, our results provide evidence that the neural substrates of writing are differentially involved in reading depending on the stored knowledge for words, as revealed by the fine-grained response of several regions including the left superior parietal lobule and left precentral gyrus / superior frontal sulcus to the experimental manipulations. Training modality and the linguistic properties of the characters also impacted the response of the left mid-fusiform gyrus, confirming its involvement as the brain region where linguistic, visual and sensorimotor information converge during orthographic processing. At the behavioral level, global handwriting quality during the training sessions was positively correlated to the final translation performance. Our results demonstrate substantial overlap in the neural substrates of reading and writing, and indicate that some regions sustaining handwriting are differentially involved in reading depending on the type of knowledge associated with words. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Nguyen, Thinh; Potter, Thomas; Grossman, Robert; Zhang, Yingchun
2018-06-01
Objective. Neuroimaging has been employed as a promising approach to advance our understanding of brain networks in both basic and clinical neuroscience. Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) represent two neuroimaging modalities with complementary features; EEG has high temporal resolution and low spatial resolution while fMRI has high spatial resolution and low temporal resolution. Multimodal EEG inverse methods have attempted to capitalize on these properties but have been subjected to localization error. The dynamic brain transition network (DBTN) approach, a spatiotemporal fMRI constrained EEG source imaging method, has recently been developed to address these issues by solving the EEG inverse problem in a Bayesian framework, utilizing fMRI priors in a spatial and temporal variant manner. This paper presents a computer simulation study to provide a detailed characterization of the spatial and temporal accuracy of the DBTN method. Approach. Synthetic EEG data were generated in a series of computer simulations, designed to represent realistic and complex brain activity at superficial and deep sources with highly dynamical activity time-courses. The source reconstruction performance of the DBTN method was tested against the fMRI-constrained minimum norm estimates algorithm (fMRIMNE). The performances of the two inverse methods were evaluated both in terms of spatial and temporal accuracy. Main results. In comparison with the commonly used fMRIMNE method, results showed that the DBTN method produces results with increased spatial and temporal accuracy. The DBTN method also demonstrated the capability to reduce crosstalk in the reconstructed cortical time-course(s) induced by neighboring regions, mitigate depth bias and improve overall localization accuracy. Significance. The improved spatiotemporal accuracy of the reconstruction allows for an improved characterization of complex neural activity. This improvement can be extended to any subsequent brain connectivity analyses used to construct the associated dynamic brain networks.
-
Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki
2016-01-01
Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768
-
Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3
Riquelme, Denise; Silva, Ian; Philp, Ashleigh M.; Huidobro-Toro, Juan P.; Cerda, Oscar; Trimmer, James S.; Leiva-Salcedo, Elias
2018-01-01
TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood. PMID:29440991
-
Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3.
Riquelme, Denise; Silva, Ian; Philp, Ashleigh M; Huidobro-Toro, Juan P; Cerda, Oscar; Trimmer, James S; Leiva-Salcedo, Elias
2018-01-01
TRPM4 is a Ca 2+ -activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood.
-
Ginsberg, M D; Chang, J Y; Kelley, R E; Yoshii, F; Barker, W W; Ingenito, G; Boothe, T E
1988-02-01
To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.
-
Going local: insights from EEG and stereo-EEG studies of the human sleep-wake cycle.
Ferrara, Michele; De Gennaro, Luigi
2011-01-01
In the present paper, we reviewed a large body of evidence, mainly from quantitative EEG studies of our laboratory, supporting the notion that sleep is a local and use-dependent process. Quantitative analyses of sleep EEG recorded from multiple cortical derivations clearly indicate that every sleep phenomenon, from sleep onset to the awakening, is strictly local in nature. Sleep onset first occurs in frontal areas, and a frontal predominance of low-frequency power persists in the first part of the night, when the homeostatic processes mainly occur, and then it vanishes. Upon awakening, we showed an asynchronous EEG activation of different cortical areas, the more anterior ones being the first to wake up. During extended periods of wakefulness, the increase of sleepiness-related low-EEG frequencies is again evident over the frontal derivations. Similarly, experimental manipulations of sleep length by total sleep deprivation, partial sleep curtailment or even selective slow-wave sleep deprivation lead to a slow-wave activity rebound localized especially on the anterior derivations. Thus, frontal areas are crucially involved in sleep homeostasis. According to the local use-dependent theory, this would derive from a higher sleep need of the frontal cortex, which in turn is due to its higher levels of activity during wakefulness. The fact that different brain regions can simultaneously exhibit different sleep intensities indicates that sleep is not a spatially global and uniform state, as hypothesized in the theory. We have also reviewed recent evidence of localized effects of learning and plasticity on EEG sleep measures. These studies provide crucial support to a key concept in the theory, the one claiming that local sleep characteristics should be use-dependent. Finally, we have reported data corroborating the notion that sleep is not necessarily present simultaneously in the entire brain. Our stereo-EEG recordings clearly indicate that sleep and wakefulness can co-exist in different areas, suggesting that vigilance states are not necessarily temporally discrete states. We conclude that understanding local variations in sleep propensity and depth, especially as a result of brain plasticity, may provide in the near future insightful hints into the fundamental functions of sleep.
-
Localization of the peroxisome proliferator-activated receptor in the brain.
Kainu, T; Wikström, A C; Gustafsson, J A; Pelto-Huikko, M
1994-12-20
This paper describes the localization of the alpha-type peroxisome proliferator-activated receptor (PPAR alpha) in the rat brain using immunocytochemistry and in situ hybridization. Expression of PPAR alpha mRNA was highest in the granular cells of the cerebellar cortex and in the dentate gyrus, with a somewhat lower expression in areas CA1-CA4 of the hippocampus. PPAR alpha mRNA was also found in some neurones of the cerebral cortex (layers II-IV) and the molecular layer of the cerebellar cortex, and in the olfactory tubercle. Immunocytochemistry revealed nuclear PPAR alpha-immunoreactivity (-IR) in the same areas as seen with the in situ hybridization. Furthermore, PPAR alpha-IR was also localized in oligodendrocytes, whereas the other glial cell types appeared to lack PPAR alpha. These results suggest that peroxisome proliferators and chemicals acting similarly have effects on discrete populations of neurones. The presence of PPAR alpha in oligodendrocytes lends further support to the suggestion that peroxisomes are important in the assembly and degradation of myelin.
-
Lv, Kun; Fan, Yi-Hong; Xu, Li; Xu, Mao-Sheng
2017-05-28
Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.
-
Artistic creativity, style and brain disorders.
Bogousslavsky, Julien
2005-01-01
The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion. (c) 2005 S. Karger AG, Basel
-
Almeida-Corrêa, Suellen; Czisch, Michael; Wotjak, Carsten T
2018-01-01
Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo non-invasive whole-brain mapping of neuronal activity. Mn 2+ enters active neurons via voltage-gated calcium channels and increases local contrast in T 1 -weighted images. Given the property of Mn 2+ of axonal transport, this technique can also be used for tract tracing after local administration of the contrast agent. However, MEMRI is still not widely employed in basic research due to the lack of a complete description of the Mn 2+ dynamics in the brain. Here, we sought to investigate how the activity state of neurons modulates interneuronal Mn 2+ transport. To this end, we injected mice with low dose MnCl 2 2. (i.p., 20 mg/kg; repeatedly for 8 days) followed by two MEMRI scans at an interval of 1 week without further MnCl 2 injections. We assessed changes in T 1 contrast intensity before (scan 1) and after (scan 2) partial sensory deprivation (unilateral whisker trimming), while keeping the animals in a sensory enriched environment. After correcting for the general decay in Mn 2+ content, whole brain analysis revealed a single cluster with higher signal in scan 1 compared to scan 2: the left barrel cortex corresponding to the right untrimmed whiskers. In the inverse contrast (scan 2 > scan 1), a number of brain structures, including many efferents of the left barrel cortex were observed. These results suggest that continuous neuronal activity elicited by ongoing sensory stimulation accelerates Mn 2+ transport from the uptake site to its projection terminals, while the blockage of sensory-input and the resulting decrease in neuronal activity attenuates Mn 2+ transport. The description of this critical property of Mn 2+ dynamics in the brain allows a better understanding of MEMRI functional mechanisms, which will lead to more carefully designed experiments and clearer interpretation of the results.
-
Relaxation techniques for stress
... of your body. These sensors measure your skin temperature, brain waves, breathing, and muscle activity. You can ... more about any of these techniques through local classes, books, videos, or online. Alternative Names Relaxation response ...
-
Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin
2014-01-01
Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567
-
Mills, Travis; Lalancette, Marc; Moses, Sandra N; Taylor, Margot J; Quraan, Maher A
2012-07-01
Magnetoencephalography provides precise information about the temporal dynamics of brain activation and is an ideal tool for investigating rapid cognitive processing. However, in many cognitive paradigms visual stimuli are used, which evoke strong brain responses (typically 40-100 nAm in V1) that may impede the detection of weaker activations of interest. This is particularly a concern when beamformer algorithms are used for source analysis, due to artefacts such as "leakage" of activation from the primary visual sources into other regions. We have previously shown (Quraan et al. 2011) that we can effectively reduce leakage patterns and detect weak hippocampal sources by subtracting the functional images derived from the experimental task and a control task with similar stimulus parameters. In this study we assess the performance of three different subtraction techniques. In the first technique we follow the same post-localization subtraction procedures as in our previous work. In the second and third techniques, we subtract the sensor data obtained from the experimental and control paradigms prior to source localization. Using simulated signals embedded in real data, we show that when beamformers are used, subtraction prior to source localization allows for the detection of weaker sources and higher localization accuracy. The improvement in localization accuracy exceeded 10 mm at low signal-to-noise ratios, and sources down to below 5 nAm were detected. We applied our techniques to empirical data acquired with two different paradigms designed to evoke hippocampal and frontal activations, and demonstrated our ability to detect robust activations in both regions with substantial improvements over image subtraction. We conclude that removal of the common-mode dominant sources through data subtraction prior to localization further improves the beamformer's ability to project the n-channel sensor-space data to reveal weak sources of interest and allows more accurate localization.
-
Egidi, Giovanna; Caramazza, Alfonso
2016-10-01
This research studies the neural systems underlying two integration processes that take place during natural discourse comprehension: consistency evaluation and passive comprehension. Evaluation was operationalized with a consistency judgment task and passive comprehension with a passive listening task. Using fMRI, the experiment examined the integration of incoming sentences with more recent, local context and with more distal, global context in these two tasks. The stimuli were stories in which we manipulated the consistency of the endings with the local context and the relevance of the global context for the integration of the endings. A whole-brain analysis revealed several differences between the two tasks. Two networks previously associated with semantic processing and attention orienting showed more activation during the judgment than the passive listening task. A network previously associated with episodic memory retrieval and construction of mental scenes showed greater activity when global context was relevant, but only during the judgment task. This suggests that evaluation, more than passive listening, triggers the reinstantiation of global context and the construction of a rich mental model for the story. Finally, a network previously linked to fluent updating of a knowledge base showed greater activity for locally consistent endings than inconsistent ones, but only during passive listening, suggesting a mode of comprehension that relies on a local scope approach to language processing. Taken together, these results show that consistency evaluation and passive comprehension weigh differently on distal and local information and are implemented, in part, by different brain networks.
-
Roselli, Charles E; Finn, Timothy J; Ronnekleiv-Kelly, Sean M; Tanchuck, Michelle A; Kaufman, Katherine R; Finn, Deborah A
2011-12-01
Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. Published by Elsevier Inc.
-
Roselli, Charles E.; Finn, Tim J.; Ronnekleiv-Kelly, Sean M.; Tanchuck, Michelle A.; Kaufman, Katherine R.; Finn, Deborah A.
2011-01-01
Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone, WSP) and found that Srd5a1 was down-regulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72 h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. PMID:21917407
-
Ball, Kelly K; Cruz, Nancy F; Mrak, Robert E; Dienel, Gerald A
2010-01-01
Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-14C]glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-14C]glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss. Brief infusion of [1-14C]glucose and -[14C]lactate into the inferior colliculus of conscious rats during acoustic stimulation labeled the meninges, consistent with perivascular clearance of [14C]metabolites from interstitial fluid. Microinfusion of Evans blue albumin and amyloid-β1−40 (Aβ) caused perivascular labeling in the inferior colliculus, labeled the surrounding meninges, and Aβ-labeled-specific blood vessels in the caudate and olfactory bulb and was deposited in cervical lymph nodes. Efflux of extracellular glucose, lactate, and Aβ into perivascular fluid pathways is a normal route for clearance of material from the inferior colliculus that contributes to underestimates of brain energetics. Convergence of ‘watershed' drainage to common pathways may facilitate perivascular amyloid plaque formation and pathway obstruction in Alzheimer's disease. PMID:19794399
-
Pomann, Gina-Maria; Sweeney, Elizabeth M; Reich, Daniel S; Staicu, Ana-Maria; Shinohara, Russell T
2015-09-10
Multiple sclerosis (MS) is an immune-mediated neurological disease that causes morbidity and disability. In patients with MS, the accumulation of lesions in the white matter of the brain is associated with disease progression and worse clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is indicative of more active disease-related processes and is a primary outcome considered in clinical trials of treatments for MS. Such abnormalities in active MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during which patients receive an intravenous infusion of a costly magnetic contrast agent. In some instances, the contrast agents can have toxic effects. Recently, local image regression techniques have been shown to have modest performance for assessing the integrity of the blood-brain barrier based on imaging without contrast agents. These models have centered on the problem of cross-sectional classification in which patients are imaged at a single study visit and pre-contrast images are used to predict post-contrast imaging. In this paper, we extend these methods to incorporate historical imaging information, and we find the proposed model to exhibit improved performance. We further develop scan-stratified case-control sampling techniques that reduce the computational burden of local image regression models, while respecting the low proportion of the brain that exhibits abnormal vascular permeability. Copyright © 2015 John Wiley & Sons, Ltd.
-
Sleep: A synchrony of cell activity-driven small network states
Krueger, James M.; Huang, Yanhua; Rector, David M.; Buysse, Daniel J.
2013-01-01
We posit a bottom-up sleep regulatory paradigm in which state changes are initiated within small networks as a consequence of local cell activity. Bottom-up regulatory mechanisms are prevalent throughout nature, occurring in vastly different systems and levels of organization. Synchronization of state without top-down regulation is a fundamental property of large collections of small semi-autonomous entities. We posit that such synchronization mechanisms are sufficient and necessary for whole organism sleep onset. Within brain we posit that small networks of highly interconnected neurons and glia, e.g. cortical columns, are semi-autonomous units oscillating between sleep-like and wake-like states. We review evidence showing that cells, small networks, and regional areas of brain share sleep-like properties with whole animal sleep. A testable hypothesis focused on how sleep is initiated within local networks is presented. We posit that the release of cell activity-dependent molecules, such as ATP and nitric oxide, into the extracellular space initiates state changes within the local networks where they are produced. We review mechanisms of ATP induction of sleep regulatory substances (SRS) and their actions on receptor trafficking. Finally, we provide an example of how such local metabolic and state changes provide mechanistic explanations for clinical conditions such as insomnia. PMID:23651209
-
Functional brain imaging predicts public health campaign success.
Falk, Emily B; O'Donnell, Matthew Brook; Tompson, Steven; Gonzalez, Richard; Dal Cin, Sonya; Strecher, Victor; Cummings, Kenneth Michael; An, Lawrence
2016-02-01
Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a 'self-localizer' defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400,000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R(2) up to 0.65) and (ii) this relationship depends on message content-self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
-
Noninvasive diffusive optical imaging of the auditory response to birdsong in the zebra finch
Lee, James V.; Maclin, Edward L.; Low, Kathy A.; Gratton, Gabriele; Fabiani, Monica; Clayton, David F.
2013-01-01
Songbirds communicate by learned vocalizations with concomitant changes in neurophysiological and genomic activities in discrete parts of the brain. Here we tested a novel implementation of diffusive optical imaging (also known as diffuse optical imaging, DOI) for monitoring brain physiology associated with vocal signal perception. DOI noninvasively measures brain activity using red and near-infrared light delivered through optic fibers (optodes) resting on the scalp. DOI does not harm subjects, so it raises the possibility of repeatedly measuring brain activity and the effects of accumulated experience in the same subject over an entire life span, all while leaving tissue intact for further study. We developed a custom-made apparatus for interfacing optodes to the zebra finch (Taeniopygia guttata) head using 3D modeling software and rapid prototyping technology, and applied it to record responses to presentations of birdsong in isoflurane-anesthetized zebra finches. We discovered a subtle but significant difference between the hemoglobin spectra of zebra finches and mammals which has a major impact in how hemodynamic responses are interpreted in the zebra finch. Our measured responses to birdsong playback were robust, highly repeatable, and readily observed in single trials. Responses were complex in shape and closely paralleled responses described in mammals. They were localized to the caudal medial portion of the brain, consistent with response localization from prior gene expression, electrophysiological, and functional magnetic resonance imaging studies. These results define an approach for collecting neurophysiological data from songbirds that should be applicable to diverse species and adaptable for studies in awake behaving animals. PMID:23322445
-
Traumatic brain injury: an overview of pathobiology with emphasis on military populations
Cernak, Ibolja; Noble-Haeusslein, Linda J
2010-01-01
This review considers the pathobiology of non-impact blast-induced neurotrauma (BINT). The pathobiology of traumatic brain injury (TBI) has been historically studied in experimental models mimicking features seen in the civilian population. These brain injuries are characterized by primary damage to both gray and white matter and subsequent evolution of secondary pathogenic events at the cellular, biochemical, and molecular levels, which collectively mediate widespread neurodegeneration. An emerging field of research addresses brain injuries related to the military, in particular blast-induced brain injuries. What is clear from the effort to date is that the pathobiology of military TBIs, particularly BINT, has characteristics not seen in other types of brain injury, despite similar secondary injury cascades. The pathobiology of primary BINT is extremely complex. It comprises systemic, local, and cerebral responses interacting and often occurring in parallel. Activation of the autonomous nervous system, sudden pressure-increase in vital organs such as lungs and liver, and activation of neuroendocrine-immune system are among the most important mechanisms significantly contributing to molecular changes and cascading injury mechanisms in the brain. PMID:19809467
-
Balconi, Michela; Vanutelli, Maria Elide
2016-01-01
The present research explored the effect of cross-modal integration of emotional cues (auditory and visual (AV)) compared with only visual (V) emotional cues in observing interspecies interactions. The brain activity was monitored when subjects processed AV and V situations, which represented an emotional (positive or negative), interspecies (human-animal) interaction. Congruence (emotionally congruous or incongruous visual and auditory patterns) was also modulated. electroencephalography brain oscillations (from delta to beta) were analyzed and the cortical source localization (by standardized Low Resolution Brain Electromagnetic Tomography) was applied to the data. Frequency band (mainly low-frequency delta and theta) showed a significant brain activity increasing in response to negative compared to positive interactions within the right hemisphere. Moreover, differences were found based on stimulation type, with an increased effect for AV compared with V. Finally, delta band supported a lateralized right dorsolateral prefrontal cortex (DLPFC) activity in response to negative and incongruous interspecies interactions, mainly for AV. The contribution of cross-modality, congruence (incongruous patterns), and lateralization (right DLPFC) in response to interspecies emotional interactions was discussed at light of a "negative lateralized effect."
-
Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery
Liew, Sook-Lei; Santarnecchi, Emilliano; Buch, Ethan R.; Cohen, Leonardo G.
2014-01-01
Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation. PMID:25018714
-
CONTROL OF SLEEP AND WAKEFULNESS
Brown, Ritchie E.; Basheer, Radhika; McKenna, James T.; Strecker, Robert E.; McCarley, Robert W.
2013-01-01
This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making. PMID:22811426
-
Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato
2011-01-01
The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209
-
Marzullo, T C; Dudley, J R; Miller, C R; Trejo, L; Kipke, D R
2005-01-01
Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.
-
Neurovascular coupling and energy metabolism in the developing brain
Kozberg, M.; Hillman, E.
2016-01-01
In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418
-
NASA Astrophysics Data System (ADS)
Natale, Joseph; Hentschel, George
Firing-rate networks offer a coarse model of signal propagation in the brain. Here we analyze sparse, 2D planar firing-rate networks with no synapses beyond a certain cutoff distance. Additionally, we impose Dale's Principle to ensure that each neuron makes only or inhibitory outgoing connections. Using spectral methods, we find that the number of neurons participating in excitations of the network becomes insignificant whenever the connectivity cutoff is tuned to a value near or below the average interneuron separation. Further, neural activations exceeding a certain threshold stay confined to a small region of space. This behavior is an instance of Anderson localization, a disorder-induced phase transition by which an information channel is rendered unable to transmit signals. We discuss several potential implications of localization for both local and long-range computation in the brain. This work was supported in part by Grants JSMF/ 220020321 and NSF/IOS/1208126.
-
Havlík, Marek
2017-01-01
The first step toward a modern understanding of fMRI resting brain activity was made by Bharat Biswal in 1995. This surprising, and at first rejected, discovery is now associated with many resting state networks, notably the famous default mode network (DMN). Resting state activity and DMN significantly reassessed our traditional beliefs and conventions about the functioning of the brain. For the majority of the twentieth century, neuroscientists assumed that the brain is mainly the "reactive engine" to the environment operating mostly through stimulation. This "reactive convention" was very influential and convenient for the goals of twentieth century neuroscience-non-invasive functional localization based on stimulation. Largely unchallenged, "reactive convention" determined the direction of scientific research for a long time and became the "reactive paradigm" of the twentieth century. Resting state activity brought knowledge that was quite different of the "reactive paradigm." Current research of the DMN, probably the best known resting state network, leads to entirely new observations and conclusions, which were not achievable from the perspective of the "reactive paradigm." This shift from reactive activity to resting state activity of the brain is accompanied by an important question: "Can resting state activity be considered a scientific revolution and the new paradigm of neuroscience, or is it only significant for one branch of neuroscience, such as fMRI?"
-
Separating brain processing of pain from that of stimulus intensity.
Oertel, Bruno G; Preibisch, Christine; Martin, Till; Walter, Carmen; Gamer, Matthias; Deichmann, Ralf; Lötsch, Jörn
2012-04-01
Regions of the brain network activated by painful stimuli are also activated by nonpainful and even nonsomatosensory stimuli. We therefore analyzed where the qualitative change from nonpainful to painful perception at the pain thresholds is coded. Noxious stimuli of gaseous carbon dioxide (n = 50) were applied to the nasal mucosa of 24 healthy volunteers at various concentrations from 10% below to 10% above the individual pain threshold. Functional magnetic resonance images showed that these trigeminal stimuli activated brain regions regarded as the "pain matrix." However, most of these activations, including the posterior insula, the primary and secondary somatosensory cortex, the amygdala, and the middle cingulate cortex, were associated with quantitative changes in stimulus intensity and did not exclusively reflect the qualitative change from nonpainful to pain. After subtracting brain activations associated with quantitative changes in the stimuli, the qualitative change, reflecting pain-exclusive activations, could be localized mainly in the posterior insular cortex. This shows that cerebral processing of noxious stimuli focuses predominately on the quantitative properties of stimulus intensity in both their sensory and affective dimensions, whereas the integration of this information into the perception of pain is restricted to a small part of the pain matrix. Copyright © 2011 Wiley Periodicals, Inc.
-
Singh, H; Li, M; Hall, L; Chen, S; Sukur, S; Lu, R; Caputo, A; Meredith, A L; Stefani, E; Toro, L
2016-03-11
Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish the localization of MaxiK channel in the mouse brain mitochondria and demonstrate the interaction of MaxiK channel with GAT3 and HSP60 in neurons. The interaction of MaxiK channel with GAT3 opens the possibility of a role of MaxiK channel in GABA homeostasis and signaling. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
-
Maldonado-Devincci, Antoniette M.; Beattie, Matthew C.; Morrow, Danielle H.; McKinley, Raechel E.; Cook, Jason B.; O’Buckley, Todd K.
2014-01-01
Rationale Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and GABAergic neuroactive steroids contribute to homeostatic regulation of this circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and hypothalamic (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) levels in rats. However, there have not been systemic investigations of acute stress on changes in plasma and brain levels of 3α,5α-THP in mouse models. Objectives The present experiments aimed to assess circulating and local brain levels of 3α,5α-THP following acute FSS in C57BL/6J mice. Methods Mice were exposed to FSS (10 min), and 50 min later, blood and brains were collected. Circulating pregnenolone and 3α,5α-THP levels were assessed in serum. Free-floating brain sections (40 µm, four to five sections/region) were immunostained and analyzed in cortical and limbic brain structures. Results FSS decreased circulating 3α,5α-THP (−41.6± 10.4 %) and reduced 3α,5α-THP immunolabeling in the paraventricular nucleus of the hypothalamus (−15.2±5.7 %), lateral amygdala (LA, −31.1±13.4 %), and nucleus accumbens (NAcc) shell (−31.9±14.6). Within the LA, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter were localized in 3α,5α-THP-positively stained cells, while in the NAcc shell, only VGLUT1 was localized in 3α,5α-THP-positively stained cells, suggesting that both glutamatergic and GABAergic cells within the LA are 3α,5α-THP-positive, while in the NAcc shell, 3α,5α-THP only localizes to glutamatergic cells. Conclusions The decrease in circulating and brain levels of 3α,5α-THP may be due to alterations in the biosynthesis/ metabolism or changes in the regulation of the HPA axis following FSS. Changes in GABAergic neuroactive steroids in response to stress likely mediate functional adaptations in neuronal activity. This may provide a potential targeted therapeutic avenue to address maladaptive stress responsivity. PMID:24744202
-
NASA Astrophysics Data System (ADS)
Silvestri, Ludovico; Rudinskiy, Nikita; Paciscopi, Marco; Müllenbroich, Marie Caroline; Costantini, Irene; Sacconi, Leonardo; Frasconi, Paolo; Hyman, Bradley T.; Pavone, Francesco S.
2016-03-01
Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.
-
Imaging fast electrical activity in the brain with electrical impedance tomography
Aristovich, Kirill Y.; Packham, Brett C.; Koo, Hwan; Santos, Gustavo Sato dos; McEvoy, Andy; Holder, David S.
2016-01-01
Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2 ms and < 200 μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7 × 5 × 2 mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures. PMID:26348559
-
Vattikonda, Anirudh; Surampudi, Bapi Raju; Banerjee, Arpan; Deco, Gustavo; Roy, Dipanjan
2016-08-01
Computational modeling of the spontaneous dynamics over the whole brain provides critical insight into the spatiotemporal organization of brain dynamics at multiple resolutions and their alteration to changes in brain structure (e.g. in diseased states, aging, across individuals). Recent experimental evidence further suggests that the adverse effect of lesions is visible on spontaneous dynamics characterized by changes in resting state functional connectivity and its graph theoretical properties (e.g. modularity). These changes originate from altered neural dynamics in individual brain areas that are otherwise poised towards a homeostatic equilibrium to maintain a stable excitatory and inhibitory activity. In this work, we employ a homeostatic inhibitory mechanism, balancing excitation and inhibition in the local brain areas of the entire cortex under neurological impairments like lesions to understand global functional recovery (across brain networks and individuals). Previous computational and empirical studies have demonstrated that the resting state functional connectivity varies primarily due to the location and specific topological characteristics of the lesion. We show that local homeostatic balance provides a functional recovery by re-establishing excitation-inhibition balance in all areas that are affected by lesion. We systematically compare the extent of recovery in the primary hub areas (e.g. default mode network (DMN), medial temporal lobe, medial prefrontal cortex) as well as other sensory areas like primary motor area, supplementary motor area, fronto-parietal and temporo-parietal networks. Our findings suggest that stability and richness similar to the normal brain dynamics at rest are achievable by re-establishment of balance. Copyright © 2016 Elsevier Inc. All rights reserved.
-
Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.
Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang
2017-11-01
Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.
-
Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R
2016-10-15
Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E.; Cohen, Leonardo G.; Birbaumer, Niels; Soekadar, Surjo R.
2016-01-01
Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796
-
Williams, Anthony J; Zhou, Chen; Sun, Qian-Quan
2016-01-01
Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5-13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings. Results indicated that FL animals exhibit a high prevalence of spontaneous spike-wave discharges (SWDs), predominately during sleep (EEG), and an increase in the incidence of hyper-excitable burst/suppression activity under general anesthesia (extracellular recordings, 0.5%-3.0% isoflurane). Brief periods of burst activity in the local field potential (LFP) typically presented as an arrhythmic pattern of increased theta-alpha spectral peaks (4-12 Hz) on a background of low-amplitude delta activity (1-4 Hz), were associated with an increase in spontaneous spiking of cortical neurons, and were highly synchronized in control animals across recording sites in both cortical and subcortical layers (average cross-correlation values ranging from +0.73 to +1.0) with minimal phase shift between electrodes. However, in FL animals, cortical vs. subcortical burst activity was strongly out of phase with significantly lower cross-correlation values compared to controls (average values of -0.1 to +0.5, P < 0.05 between groups). In particular, a marked reduction in the level of synchronous burst activity was observed, the closer the recording electrodes were to the malformation (Pearson's Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity also included a spike or spike-wave pattern similar to the SWDs observed in unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable pattern of burst activity induced by anesthesia and disrupted field potential synchrony between cortical and subcortical brain regions near the site of the cortical malformation. Monitoring the altered electrophysiology of burst activity under general anesthesia with multi-dimensional micro-electrode arrays may serve to define distinct neurophysiological biomarkers of epileptogenesis in human brain and improve techniques for surgical resection of epileptogenic malformed brain tissue.
-
Wang, Chenbo; Oyserman, Daphna; Liu, Qiang; Li, Hong; Han, Shihui
2013-01-01
Self-construal priming modulates human behavior and associated neural activity. However, the neural activity associated with the self-construal priming procedure itself remains unknown. It is also unclear whether and how self-construal priming affects neural activity prior to engaging in a particular task. To address this gap, we scanned Chinese adults, using functional magnetic resonance imaging, during self-construal priming and a following resting state. We found that, relative to a calculation task, both interdependent and independent self-construal priming activated the ventral medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC). The contrast of interdependent vs. independent self-construal priming also revealed increased activity in the dorsal MPFC and left middle frontal cortex. The regional homogeneity analysis of the resting-state activity revealed increased local synchronization of spontaneous activity in the dorsal MPFC but decreased local synchronization of spontaneous activity in the PCC when contrasting interdependent vs. independent self-construal priming. The functional connectivity analysis of the resting-state activity, however, did not show significant difference in synchronization of activities in remote brain regions between different priming conditions. Our findings suggest that accessible collectivistic/individualistic mind-set induced by self-construal priming is associated with modulations of both task-related and resting-state activity in the default mode network.
-
Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.
Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru
2016-05-01
The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.
-
Zhang, Jiang; Li, Yuyao; Chen, Huafu; Ding, Jurong; Yuan, Zhen
2016-11-04
In this study, small-world network analysis was performed to identify the similarities and differences between functional brain networks for right- and left-hand motor imageries (MIs). First, Pearson correlation coefficients among the nodes within the functional brain networks from healthy subjects were calculated. Then, small-world network indicators, including the clustering coefficient, the average path length, the global efficiency, the local efficiency, the average node degree, and the small-world index, were generated for the functional brain networks during both right- and left-hand MIs. We identified large differences in the small-world network indicators between the functional networks during MI and in the random networks. More importantly, the functional brain networks underlying the right- and left-hand MIs exhibited similar small-world properties in terms of the clustering coefficient, the average path length, the global efficiency, and the local efficiency. By contrast, the right- and left-hand MI brain networks showed differences in small-world characteristics, including indicators such as the average node degree and the small-world index. Interestingly, our findings also suggested that the differences in the activity intensity and range, the average node degree, and the small-world index of brain networks between the right- and left-hand MIs were associated with the asymmetry of brain functions.
-
Characterization of Novel Cytoplasmic PARP in the Brain of Octopus vulgaris
DE LISA, EMILIA; DE MAIO, ANNA; MOROZ, LEONID L.; MOCCIA, FRANCESCO; MENNELLA, MARIA ROSARIA FARAONE; DI COSMO, ANNA
2014-01-01
Recent investigation has focused on the participation of the poly (ADP-ribose) polymerase (PARP) reaction in the invertebrate central nervous system (CNS) during the process of long-term memory (LTM). In this paper, we characterize, localize, and assign a possible role to a cytoplasmic PARP in the brain of Octopus vulgaris. PARP activity was assayed in optic lobes, supraesophageal mass, and optic nerves. The highest levels of enzyme were found in the cytoplasmic fraction. Hyper-activation of the enzyme was detected in Octopus brain after visual discrimination training. Finally, cytoplasmic PARP was found to inhibit Octopus vulgaris actin polymerization. We propose that the cytoplasmic PARP plays a role in vivo to induce the cytoskeletonal reorganization that occurs during learning-induced neuronal plasticity. PMID:22815366
-
Williams, Shawniqua T; Conte, Mary M; Goldfine, Andrew M; Noirhomme, Quentin; Gosseries, Olivia; Thonnard, Marie; Beattie, Bradley; Hersh, Jennifer; Katz, Douglas I; Victor, Jonathan D; Laureys, Steven; Schiff, Nicholas D
2013-01-01
Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. DOI: http://dx.doi.org/10.7554/eLife.01157.001 PMID:24252875
-
Resting state electrical brain activity and connectivity in fibromyalgia
Vanneste, Sven; Ost, Jan; Van Havenbergh, Tony; De Ridder, Dirk
2017-01-01
The exact mechanism underlying fibromyalgia is unknown, but increased facilitatory modulation and/or dysfunctional descending inhibitory pathway activity are posited as possible mechanisms contributing to sensitization of the central nervous system. The primary goal of this study is to identify a fibromyalgia neural circuit that can account for these abnormalities in central pain. The second goal is to gain a better understanding of the functional connectivity between the default and the executive attention network (salience network plus dorsal lateral prefrontal cortex) in fibromyalgia. We examine neural activity associated with fibromyalgia (N = 44) and compare these with healthy controls (N = 44) using resting state source localized EEG. Our data support an important role of the pregenual anterior cingulate cortex but also suggest that the degree of activation and the degree of integration between different brain areas is important. The inhibition of the connectivity between the dorsal lateral prefrontal cortex and the posterior cingulate cortex on the pain inhibitory pathway seems to be limited by decreased functional connectivity with the pregenual anterior cingulate cortex. Our data highlight the functional dynamics of brain regions integrated in brain networks in fibromyalgia patients. PMID:28650974
-
2017-01-01
Decoding neural activities related to voluntary and involuntary movements is fundamental to understanding human brain motor circuits and neuromotor disorders and can lead to the development of neuromotor prosthetic devices for neurorehabilitation. This study explores using recorded deep brain local field potentials (LFPs) for robust movement decoding of Parkinson's disease (PD) and Dystonia patients. The LFP data from voluntary movement activities such as left and right hand index finger clicking were recorded from patients who underwent surgeries for implantation of deep brain stimulation electrodes. Movement-related LFP signal features were extracted by computing instantaneous power related to motor response in different neural frequency bands. An innovative neural network ensemble classifier has been proposed and developed for accurate prediction of finger movement and its forthcoming laterality. The ensemble classifier contains three base neural network classifiers, namely, feedforward, radial basis, and probabilistic neural networks. The majority voting rule is used to fuse the decisions of the three base classifiers to generate the final decision of the ensemble classifier. The overall decoding performance reaches a level of agreement (kappa value) at about 0.729 ± 0.16 for decoding movement from the resting state and about 0.671 ± 0.14 for decoding left and right visually cued movements. PMID:29201041
-
Changes in Brain Network Efficiency and Working Memory Performance in Aging
Stanley, Matthew L.; Simpson, Sean L.; Dagenbach, Dale; Lyday, Robert G.; Burdette, Jonathan H.; Laurienti, Paul J.
2015-01-01
Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory. PMID:25875001
-
Changes in brain network efficiency and working memory performance in aging.
Stanley, Matthew L; Simpson, Sean L; Dagenbach, Dale; Lyday, Robert G; Burdette, Jonathan H; Laurienti, Paul J
2015-01-01
Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.
-
Fu, Zening; Tu, Yiheng; Di, Xin; Du, Yuhui; Pearlson, G D; Turner, J A; Biswal, Bharat B; Zhang, Zhiguo; Calhoun, V D
2017-09-20
The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Yano, Kazuo; Kawasaki, Koh; Hattori, Tsuyoshi; Tawara, Shunsuke; Toshima, Yoshinori; Ikegaki, Ichiro; Sasaki, Yasuo; Satoh, Shin-ichi; Asano, Toshio; Seto, Minoru
2008-10-10
Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.
-
Local Use-Dependent Sleep in Wakefulness Links Performance Errors to Learning
Quercia, Angelica; Zappasodi, Filippo; Committeri, Giorgia; Ferrara, Michele
2018-01-01
Sleep and wakefulness are no longer to be considered as discrete states. During wakefulness brain regions can enter a sleep-like state (off-periods) in response to a prolonged period of activity (local use-dependent sleep). Similarly, during nonREM sleep the slow-wave activity, the hallmark of sleep plasticity, increases locally in brain regions previously involved in a learning task. Recent studies have demonstrated that behavioral performance may be impaired by off-periods in wake in task-related regions. However, the relation between off-periods in wake, related performance errors and learning is still untested in humans. Here, by employing high density electroencephalographic (hd-EEG) recordings, we investigated local use-dependent sleep in wake, asking participants to repeat continuously two intensive spatial navigation tasks. Critically, one task relied on previous map learning (Wayfinding) while the other did not (Control). Behaviorally awake participants, who were not sleep deprived, showed progressive increments of delta activity only during the learning-based spatial navigation task. As shown by source localization, delta activity was mainly localized in the left parietal and bilateral frontal cortices, all regions known to be engaged in spatial navigation tasks. Moreover, during the Wayfinding task, these increments of delta power were specifically associated with errors, whose probability of occurrence was significantly higher compared to the Control task. Unlike the Wayfinding task, during the Control task neither delta activity nor the number of errors increased progressively. Furthermore, during the Wayfinding task, both the number and the amplitude of individual delta waves, as indexes of neuronal silence in wake (off-periods), were significantly higher during errors than hits. Finally, a path analysis linked the use of the spatial navigation circuits undergone to learning plasticity to off periods in wake. In conclusion, local sleep regulation in wakefulness, associated with performance failures, could be functionally linked to learning-related cortical plasticity. PMID:29666574
-
Saito, Mitsuo; Chakraborty, Goutam; Shah, Relish; Mao, Rui-Fen; Kumar, Asok; Yang, Dun-Sheng; Dobrenis, Kostantin; Saito, Mariko
2012-01-01
GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase-3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c release and caspase-3 activation in the 7-day–old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration. PMID:22372857
-
Fingelkurts, Alexander A.; Fingelkurts, Andrew A.
2014-01-01
For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292
-
Buchweitz, Augusto; Mason, Robert A.; Meschyan, Gayane; Keller, Timothy A.; Just, Marcel Adam
2014-01-01
Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is to demonstrate how the brain system for text comprehension adapts to varying perceptual and knowledge conditions. PMID:25463816
-
Buchweitz, Augusto; Mason, Robert A; Meschyan, Gayane; Keller, Timothy A; Just, Marcel Adam
2014-12-01
Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is that the brain system for text comprehension adapts to varying perceptual and knowledge conditions. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Active Learning with Statistical Models.
1995-01-01
Active Learning with Statistical Models ASC-9217041, NSF CDA-9309300 6. AUTHOR(S) David A. Cohn, Zoubin Ghahramani, and Michael I. Jordan 7. PERFORMING...TERMS 15. NUMBER OF PAGES Al, MIT, Artificial Intelligence, active learning , queries, locally weighted 6 regression, LOESS, mixtures of gaussians...COMPUTATIONAL LEARNING DEPARTMENT OF BRAIN AND COGNITIVE SCIENCES A.I. Memo No. 1522 January 9. 1995 C.B.C.L. Paper No. 110 Active Learning with
-
Art and brain: insights from neuropsychology, biology and evolution.
Zaidel, Dahlia W
2010-02-01
Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation.
-
Art and brain: insights from neuropsychology, biology and evolution
Zaidel, Dahlia W
2010-01-01
Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation. PMID:19490399
-
Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation
Gründemann, Jan; Clark, Beverley A.
2015-01-01
Summary Functional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1) by local, activity-dependent calcium (Ca2+) influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells. PMID:26344775
-
Blood-brain barrier-supported neurogenesis in healthy and diseased brain.
Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B
2017-05-24
Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.
-
Individual brain structure and modelling predict seizure propagation
Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K.
2017-01-01
Abstract See Lytton (doi:10.1093/awx018) for a scientific commentary on this article. Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. PMID:28364550
-
Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien
2015-06-01
The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.
-
Kusano, Yoshikazu; Horiuchi, Tetsuyoshi; Seguchi, Tatsuya; Kakizawa, Yukinari; Tanaka, Yuichiro; Hongo, Kazuhiro
2010-01-01
Local brain herniation after removal of chronic subdural haematoma is extremely rare, especially in adult patients. This study reports a case of local brain herniation after partial membranectomy for organized chronic subdural haematoma. A 77-year-old man presented with dysarthria and dysphasia caused by local brain herniation of the right frontal lobe through a defect of the inner membrane. The herniated brain was detected by magnetic resonance (MR) imaging. The patient underwent a craniotomy to release the herniated and strangulated brain, which were consistent with the MR imaging findings. The patient recovered fully within 1 month after surgery. To date, five cases of brain herniation through the internal subdural membrane have been reported as complications of chronic subdural haematomas. All but one case occurred in the paediatric population. Urgent surgery should be performed, even if an adult patient suffers from local brain herniation, for preservation of brain function. This is the sixth reported case of brain herniation through a defect of the inner membrane and the second reported case in the adult population.
-
Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Avi; Friedman, Alon; Shelef, Ilan
2011-01-01
Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE. PMID:21436875
-
NASA Astrophysics Data System (ADS)
Krestyannikov, E.; Tohka, J.; Ruotsalainen, U.
2008-06-01
This paper presents a novel statistical approach for joint estimation of regions-of-interest (ROIs) and the corresponding time-activity curves (TACs) from dynamic positron emission tomography (PET) brain projection data. It is based on optimizing the joint objective function that consists of a data log-likelihood term and two penalty terms reflecting the available a priori information about the human brain anatomy. The developed local optimization strategy iteratively updates both the ROI and TAC parameters and is guaranteed to monotonically increase the objective function. The quantitative evaluation of the algorithm is performed with numerically and Monte Carlo-simulated dynamic PET brain data of the 11C-Raclopride and 18F-FDG tracers. The results demonstrate that the method outperforms the existing sequential ROI quantification approaches in terms of accuracy, and can noticeably reduce the errors in TACs arising due to the finite spatial resolution and ROI delineation.
-
Cao, Hengyi; Plichta, Michael M; Schäfer, Axel; Haddad, Leila; Grimm, Oliver; Schneider, Michael; Esslinger, Christine; Kirsch, Peter; Meyer-Lindenberg, Andreas; Tost, Heike
2014-01-01
The investigation of the brain connectome with functional magnetic resonance imaging (fMRI) and graph theory analyses has recently gained much popularity, but little is known about the robustness of these properties, in particular those derived from active fMRI tasks. Here, we studied the test-retest reliability of brain graphs calculated from 26 healthy participants with three established fMRI experiments (n-back working memory, emotional face-matching, resting state) and two parcellation schemes for node definition (AAL atlas, functional atlas proposed by Power et al.). We compared the intra-class correlation coefficients (ICCs) of five different data processing strategies and demonstrated a superior reliability of task-regression methods with condition-specific regressors. The between-task comparison revealed significantly higher ICCs for resting state relative to the active tasks, and a superiority of the n-back task relative to the face-matching task for global and local network properties. While the mean ICCs were typically lower for the active tasks, overall fair to good reliabilities were detected for global and local connectivity properties, and for the n-back task with both atlases, smallworldness. For all three tasks and atlases, low mean ICCs were seen for the local network properties. However, node-specific good reliabilities were detected for node degree in regions known to be critical for the challenged functions (resting-state: default-mode network nodes, n-back: fronto-parietal nodes, face-matching: limbic nodes). Between-atlas comparison demonstrated significantly higher reliabilities for the functional parcellations for global and local network properties. Our findings can inform the choice of processing strategies, brain atlases and outcome properties for fMRI studies using active tasks, graph theory methods, and within-subject designs, in particular future pharmaco-fMRI studies. © 2013 Elsevier Inc. All rights reserved.
-
Reconfigurable visible nanophotonic switch for optogenetic applications (Conference Presentation)
NASA Astrophysics Data System (ADS)
Mohanty, Aseema; Li, Qian; Tadayon, Mohammad Amin; Bhatt, Gaurang R.; Cardenas, Jaime; Miller, Steven A.; Kepecs, Adam; Lipson, Michal
2017-02-01
High spatiotemporal resolution deep-brain optical excitation for optogenetics would enable activation of specific neural populations and in-depth study of neural circuits. Conventionally, a single fiber is used to flood light into a large area of the brain with limited resolution. The scalability of silicon photonics could enable neural excitation over large areas with single-cell resolution similar to electrical probes. However, active control of these optical circuits has yet to be demonstrated for optogenetics. Here we demonstrate the first active integrated optical switch for neural excitation at 473 nm, enabling control of multiple beams for deep-brain neural stimulation. Using a silicon nitride waveguide platform, we develop a cascaded Mach-Zehnder interferometer (MZI) network located outside the brain to direct light to 8 different grating emitters located at the tip of the neural probe. We use integrated platinum microheaters to induce a local thermo-optic phase shift in the MZI to control the switch output. We measure an ON/OFF extinction ratio of >8dB for a single switch and a switching speed of 20 microseconds. We characterize the optical output of the switch by imaging its excitation of fluorescent dye. Finally, we demonstrate in vivo single-neuron optical activation from different grating emitters using a fully packaged device inserted into a mouse brain. Directly activated neurons showed robust spike firing activities with low first-spike latency and small jitter. Active switching on a nanophotonic platform is necessary for eventually controlling highly-multiplexed reconfigurable optical circuits, enabling high-resolution optical stimulation in deep-brain regions.
-
Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar
2017-01-01
Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD.
-
Kempuraj, Duraisamy; Selvakumar, Govindhasamy P.; Thangavel, Ramasamy; Ahmed, Mohammad E.; Zaheer, Smita; Raikwar, Sudhanshu P.; Iyer, Shankar S.; Bhagavan, Sachin M.; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar
2017-01-01
Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD. PMID:29302258
-
Freeman, Walter J
2007-06-01
The hypothesis is proposed that the central dynamics of the action-perception cycle has five steps: emergence from an existing macroscopic brain state of a pattern that predicts a future goal state; selection of a mesoscopic frame for action control; execution of a limb trajectory by microscopic spike activity; modification of microscopic cortical spike activity by sensory inputs; construction of mesoscopic perceptual patterns; and integration of a new macroscopic brain state. The basis is the circular causality between microscopic entities (neurons) and the mesoscopic and macroscopic entities (populations) self-organized by axosynaptic interactions. Self-organization of neural activity is bidirectional in all cortices. Upwardly the organization of mesoscopic percepts from microscopic spike input predominates in primary sensory areas. Downwardly the organization of spike outputs that direct specific limb movements is by mesoscopic fields constituting plans to achieve predicted goals. The mesoscopic fields in sensory and motor cortices emerge as frames within macroscopic activity. Part 1 describes the action-perception cycle and its derivative reflex arc qualitatively. Part 2 describes the perceptual limb of the arc from microscopic MSA to mesoscopic wave packets, and from these to macroscopic EEG and global ECoG fields that express experience-dependent knowledge in successive states. These macroscopic states are conceived to embed and control mesoscopic frames in premotor and motor cortices that are observed in local ECoG and LFP of frontoparietal areas. The fields sampled by ECoG and LFP are conceived as local patterns of neural activity in which trajectories of multiple spike activities (MSA) emerge that control limb movements. Mesoscopic frames are located by use of the analytic signal from the Hilbert transform after band pass filtering. The state variables in frames are measured to construct feature vectors by which to describe and classify frame patterns. Evidence is cited to justify use of linear analysis. The aim of the review is to enable researchers to conceive and identify goal-oriented states in brain activity for use as commands, in order to relegate the details of execution to adaptive control devices outside the brain.
-
Williams, Leanne M; Gatt, Justine M; Kuan, Stacey A; Dobson-Stone, Carol; Palmer, Donna M; Paul, Robert H; Song, Le; Costa, Paul T; Schofield, Peter R; Gordon, Evian
2009-06-01
Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males. Here, we assessed the low (MAOA-L) activity variant in relation to both brain function and a behavioral index of antisocial traits. From an initial sample of 290 healthy participants, 210 had low (MAOA-L) or high (MAOA-H) activity variants. Participants underwent a brief assessment of personality traits and event-related potential (ERP) recording during an emotion-processing task. Genotype differences in ERPs were localized using LORETA. The MAOA-L genotype was distinguished by elevated scores on the index of antisocial traits. These traits were related to altered ERPs elicited 120-280ms post-stimulus, particularly for negative emotion. Altered neural processing of anger in MAOA-L genotypes was localized to medial frontal, parietal, and superior temporo-occipital regions in males, but only to the superior occipital cortex in females. The MAOA low activity variant may increase susceptibility to antisocial traits through alterations to the neural systems for processing threat-related emotion, especially for males. Monoamines such as noradrenalin and serotonin may modulate these relationships, given that their metabolism varies according to MAOA variants, and that they modulate both emotional brain systems and antisocial aggression.
-
Category representations in the brain are both discretely localized and widely distributed.
Shehzad, Zarrar; McCarthy, Gregory
2018-06-01
Whether category information is discretely localized or represented widely in the brain remains a contentious issue. Initial functional MRI studies supported the localizationist perspective that category information is represented in discrete brain regions. More recent fMRI studies using machine learning pattern classification techniques provide evidence for widespread distributed representations. However, these latter studies have not typically accounted for shared information. Here, we find strong support for distributed representations when brain regions are considered separately. However, localized representations are revealed by using analytical methods that separate unique from shared information among brain regions. The distributed nature of shared information and the localized nature of unique information suggest that brain connectivity may encourage spreading of information but category-specific computations are carried out in distinct domain-specific regions. NEW & NOTEWORTHY Whether visual category information is localized in unique domain-specific brain regions or distributed in many domain-general brain regions is hotly contested. We resolve this debate by using multivariate analyses to parse functional MRI signals from different brain regions into unique and shared variance. Our findings support elements of both models and show information is initially localized and then shared among other regions leading to distributed representations being observed.
-
Sedeyn, Jonathan C.; Wu, Hao; Hobbs, Reilly D.; Levin, Eli C.; Nagele, Robert G.; Venkataraman, Venkat
2015-01-01
Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. PMID:26697497
-
NASA Astrophysics Data System (ADS)
Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming
2007-12-01
The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.
-
Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus
2014-01-01
Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.
-
Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus
2014-01-01
Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site. PMID:24760013
-
Wofford, Kathryn L; Harris, James P; Browne, Kevin D; Brown, Daniel P; Grovola, Michael R; Mietus, Constance J; Wolf, John A; Duda, John E; Putt, Mary E; Spiller, Kara L; Cullen, D Kacy
2017-04-01
Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI. Strikingly, microglial activation was restrained to regions proximal to individual injured neurons - as denoted by trauma-induced plasma membrane disruption - which served as epicenters of acute reactivity. Single-cell quantitative analysis showed that in areas free of traumatically permeabilized neurons, microglial density and morphology were similar between sham or following mild or severe TBI. However, microglia density increased and morphology shifted to become more reactive in proximity to injured neurons. Microglial reactivity around injured neurons was exacerbated following repetitive TBI, suggesting further amplification of acute neuroinflammatory responses. These results indicate that neuronal trauma rapidly activates microglia in a highly localized manner, and suggest that activated microglia may rapidly influence neuronal stability and/or pathophysiology after diffuse TBI. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Detection of early seizures by diffuse optical tomography
NASA Astrophysics Data System (ADS)
Zhang, Tao; Hajihashemi, M. Reza; Zhou, Junli; Carney, Paul R.; Jiang, Huabei
2015-03-01
In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.
-
White, David J; Congedo, Marco; Ciorciari, Joseph; Silberstein, Richard B
2012-03-01
Brain oscillatory correlates of spatial navigation were investigated using blind source separation (BSS) and standardized low resolution electromagnetic tomography (sLORETA) analyses of 62-channel EEG recordings. Twenty-five participants were instructed to navigate to distinct landmark buildings in a previously learned virtual reality town environment. Data from periods of navigation between landmarks were subject to BSS analyses to obtain source components. Two of these cortical sources were found to exhibit significant spectral power differences during navigation with respect to a resting eyes open condition and were subject to source localization using sLORETA. These two sources were localized as a right parietal component with gamma activation and a right medial-temporal-parietal component with activation in theta and gamma bandwidths. The parietal gamma activity was thought to reflect visuospatial processing associated with the task. The medial-temporal-parietal activity was thought to be more specific to the navigational processing, representing the integration of ego- and allo-centric representations of space required for successful navigation, suggesting theta and gamma oscillations may have a role in integrating information from parietal and medial-temporal regions. Theta activity on this medial-temporal-parietal source was positively correlated with more efficient navigation performance. Results are discussed in light of the depth and proposed closed field structure of the hippocampus and potential implications for scalp EEG data. The findings of the present study suggest that appropriate BSS methods are ideally suited to minimizing the effects of volume conduction in noninvasive recordings, allowing more accurate exploration of deep brain processes.
-
A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System.
Qin, Yan; Garrison, Brian S; Ma, Wenjiang; Wang, Rui; Jiang, Aiping; Li, Jing; Mistry, Meeta; Bronson, Roderick T; Santoro, Daria; Franco, Charlotte; Robinton, Daisy A; Stevens, Beth; Rossi, Derrick J; Lu, Chafen; Springer, Timothy A
2018-06-12
Extracellular proTGF-β is covalently linked to "milieu" molecules in the matrix or on cell surfaces and is latent until TGF-β is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-αVβ8-dependent TGF-β activation. Lrrc33 -/- mice lack CNS vascular abnormalities associated with deficiency in TGF-β-activating integrins but have microglia with a reactive phenotype and after 2 months develop ascending paraparesis with loss of myelinated axons and death by 5 months. Whole bone marrow transplantation results in selective repopulation of Lrrc33 -/- brains with WT microglia and halts disease progression. The phenotypes of WT and Lrrc33 -/- microglia in the same brain suggest that there is little spreading of TGF-β activated from one microglial cell to neighboring microglia. Our results suggest that interactions between integrin-bearing cells and cells bearing milieu molecule-associated TGF-β provide localized and selective activation of TGF-β. Copyright © 2018 Elsevier Inc. All rights reserved.
-
De Martin, Elena; Duran, Dunja; Ghielmetti, Francesco; Visani, Elisa; Aquino, Domenico; Marchetti, Marcello; Sebastiano, Davide Rossi; Cusumano, Davide; Bruzzone, Maria Grazia; Panzica, Ferruccio; Fariselli, Laura
2017-12-01
Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Snellings, André; Sagher, Oren; Anderson, David J.; Aldridge, J. Wayne
2016-01-01
Object A wavelet-based measure was developed to quantitatively assess neural background activity taken during surgical neurophysiological recordings to localize the boundaries of the subthalamic nucleus during target localization for deep brain stimulator implant surgery. Methods Neural electrophysiological data was recorded from 14 patients (20 tracks, n = 275 individual recording sites) with dopamine-sensitive idiopathic Parkinson’s disease during the target localization portion of deep brain stimulator implant surgery. During intraoperative recording the STN was identified based upon audio and visual monitoring of neural firing patterns, kinesthetic tests, and comparisons between neural behavior and known characteristics of the target nucleus. The quantitative wavelet-based measure was applied off-line using MATLAB software to measure the magnitude of the neural background activity, and the results of this analysis were compared to the intraoperative conclusions. Wavelet-derived estimates were compared to power spectral density measures. Results The wavelet-derived background levels were significantly higher in regions encompassed by the clinically estimated boundaries of the STN than in surrounding regions (STN: 225 ± 61 μV vs. ventral to STN: 112 ± 32 μV, and dorsal to STN: 136 ± 66 μV). In every track, the absolute maximum magnitude was found within the clinically identified STN. The wavelet-derived background levels provided a more consistent index with less variability than power spectral density. Conclusions The wavelet-derived background activity assessor can be calculated quickly, requires no spike sorting, and can be reliably used to identify the STN with very little subjective interpretation required. This method may facilitate rapid intraoperative identification of subthalamic nucleus borders. PMID:19344225
-
Differential effects of deep brain stimulation on verbal fluency.
Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian
2014-07-01
We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Zhu, Li; Najafizadeh, Laleh
2017-06-01
We investigate the problem related to the averaging procedure in functional near-infrared spectroscopy (fNIRS) brain imaging studies. Typically, to reduce noise and to empower the signal strength associated with task-induced activities, recorded signals (e.g., in response to repeated stimuli or from a group of individuals) are averaged through a point-by-point conventional averaging technique. However, due to the existence of variable latencies in recorded activities, the use of the conventional averaging technique can lead to inaccuracies and loss of information in the averaged signal, which may result in inaccurate conclusions about the functionality of the brain. To improve the averaging accuracy in the presence of variable latencies, we present an averaging framework that employs dynamic time warping (DTW) to account for the temporal variation in the alignment of fNIRS signals to be averaged. As a proof of concept, we focus on the problem of localizing task-induced active brain regions. The framework is extensively tested on experimental data (obtained from both block design and event-related design experiments) as well as on simulated data. In all cases, it is shown that the DTW-based averaging technique outperforms the conventional-based averaging technique in estimating the location of task-induced active regions in the brain, suggesting that such advanced averaging methods should be employed in fNIRS brain imaging studies.
-
A Bayesian Model of Category-Specific Emotional Brain Responses
Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman
2015-01-01
Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490
-
Brain hyperthermia and temperature fluctuations during sexual interaction in female rats.
Mitchum, Robert D; Kiyatkin, Eugene A
2004-03-12
Since the metabolic activity of neural cells is accompanied by heat release, brain temperature monitoring provides insight into behavior-associated changes in neural activity. In the present study, local temperatures were continuously recorded in several brain structures (nucleus accumbens, medial-preoptic hypothalamus and hippocampus) and a non-locomotor head muscle (musculus temporalis) in a receptive female rat during sexually arousing stimulation and subsequent copulatory behavior with an experienced male. Placement of the male into a neighboring compartment increased the female's temperature (approximately 0.8 degrees C) and additional, transient increases (approximately 0.2 degrees C) occurred when the rats were allowed to see and smell each other through a transparent barrier. Temperatures gradually increased further as the male repeatedly mounted and achieved intromissions, peaked 2-3 min after male's ejaculation (0.2-0.4 degrees C), and abruptly dropped until the male initiated a new copulatory cycle. Similar biphasic fluctuations accompanied subsequent copulatory cycles. Although both arousal-related temperature increases and biphasic fluctuations associated with copulatory cycles were evident in each recording location, brain sites showed consistently faster and stronger increases than the muscle, suggesting metabolic brain activation as the primary source of brain temperature fluctuations and a force behind associated changes in brain temperature. Robust brain hyperthermia and the generally similar pattern of phasic temperature fluctuations associated with individual events of sexual interaction found in males and females suggest widespread neural activation (motivational arousal) as a driving force underlying this cooperative motivated behavior in animals of both sexes. Females, however, showed different temperature changes in association with the initial (first mount or intromission) and final (ejaculation) events of each copulatory cycle, suggesting sex-specific differences in neural activity associated with the initiation and regulation of sexual behavior.
-
[Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains].
Sabel, B A
2017-02-01
Visual field defects are considered irreversible because the retina and optic nerve do not regenerate. Nevertheless, there is some potential for recovery of the visual fields. This can be accomplished by the brain, which analyses and interprets visual information and is able to amplify residual signals through neuroplasticity. Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy. This is actually the neurobiological basis of normal learning. Plasticity is maintained throughout life and can be induced by repetitively stimulating (training) brain circuits. The question now arises as to how plasticity can be utilised to activate residual vision for the treatment of visual field loss. Just as in neurorehabilitation, visual field defects can be modulated by post-lesion plasticity to improve vision in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all patients have some residual vision, the goal is to strengthen residual capacities by enhancing synaptic efficacy. New treatment paradigms have been tested in clinical studies, including vision restoration training and non-invasive alternating current stimulation. While vision training is a behavioural task to selectively stimulate "relative defects" with daily vision exercises for the duration of 6 months, treatment with alternating current stimulation (30 min. daily for 10 days) activates and synchronises the entire retina and brain. Though full restoration of vision is not possible, such treatments improve vision, both subjectively and objectively. This includes visual field enlargements, improved acuity and reaction time, improved orientation and vision related quality of life. About 70 % of the patients respond to the therapies and there are no serious adverse events. Physiological studies of the effect of alternating current stimulation using EEG and fMRI reveal massive local and global changes in the brain. These include local activation of the visual cortex and global reorganisation of neuronal brain networks. Because modulation of neuroplasticity can strengthen residual vision, the brain deserves a better reputation in ophthalmology for its role in visual rehabilitation. For patients, there is now more light at the end of the tunnel, because vision loss in some areas of the visual field defect is indeed reversible. Georg Thieme Verlag KG Stuttgart · New York.
-
[Neurofeedback for the treatment of chronic tinnitus : Review and future perspectives].
Kleinjung, T; Thüring, C; Güntensperger, D; Neff, P; Meyer, M
2018-03-01
Neurofeedback is a noninvasive neuromodulation technique employing real-time display of brain activity in terms of electroencephalography (EEG) signals to teach self-regulation of distinct patterns of brain activity or influence brain activity in a targeted manner. The benefit of this approach for control of symptoms in attention deficit disorders, hyperactivity, depression, and migraine has been proven. Studies in recent years have also repeatedly shown this treatment to improve tinnitus symptoms, although it has not become established as routine therapy. The primary focus of this review is the rational of EEG neurofeedback for tinnitus treatment and the currently available data from published studies. Furthermore, alternative neurofeedback protocols using real-time functional magnetic resonance imaging (fMRI) measurements for tinnitus control are considered. Finally, this article highlights how modern EEG analysis (source localization, connectivity) and the improving understanding of tinnitus pathology can contribute to development of more focused neurofeedback protocols for more sustainable control of tinnitus.
-
Arichi, Tomoki; Whitehead, Kimberley; Barone, Giovanni; Pressler, Ronit; Padormo, Francesco; Edwards, A David; Fabrizi, Lorenzo
2017-09-12
Electroencephalographic recordings from the developing human brain are characterized by spontaneous neuronal bursts, the most common of which is the delta brush. Although similar events in animal models are known to occur in areas of immature cortex and drive their development, their origin in humans has not yet been identified. Here, we use simultaneous EEG-fMRI to localise the source of delta brush events in 10 preterm infants aged 32-36 postmenstrual weeks. The most frequent patterns were left and right posterior-temporal delta brushes which were associated in the left hemisphere with ipsilateral BOLD activation in the insula only; and in the right hemisphere in both the insular and temporal cortices. This direct measure of neural and hemodynamic activity shows that the insula, one of the most densely connected hubs in the developing cortex, is a major source of the transient bursting events that are critical for brain maturation.
-
Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity.
Petrova, Emilia B; Dimitrova, Mashenka B; Ivanov, Ivaylo P; Pavlova, Velichka G; Dimitrova, Stella G; Kadiysky, Dimitar S
2016-06-01
Hypoxic events are known to cause substantial damage to the hippocampus, cerebellum and striatum. The impact of hypoxic shock on other brain parts is not sufficiently studied. Recent studies show that tripeptidyl peptidase I (TPPI) activity in fish is altered after a hypoxic stress pointing out at a possible enzyme involvement in response to hypoxia. Similar studies are not performed in mammals. In this work, the effect of sodium nitrite-induced acute hypoxic shock on the rat brain was studied at different post-treatment periods. Morphological changes in cerebral cortex, cerebellum, medulla oblongata, thalamus, mesencephalon and pons were assessed using silver-copper impregnation for neurodegeneration. TPPI activity was biochemically assayed and localized by enzyme histochemistry. Although less vulnerable to oxidative stress, the studied brain areas showed different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity was strictly regulated following the hypoxic stress. It was found to increase 12-24h post-treatment, then decreased followed by a slow process of recovery. The enzyme histochemistry revealed a temporary enzyme deficiency in all types of neurons. These findings indicate a possible involvement of the enzyme in rat brain response to hypoxic stress. Copyright © 2016 Elsevier GmbH. All rights reserved.
-
Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K
2014-05-01
Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.
-
Kobayashi, Takuma; Haruta, Makito; Sasagawa, Kiyotaka; Matsumata, Miho; Eizumi, Kawori; Kitsumoto, Chikara; Motoyama, Mayumi; Maezawa, Yasuyo; Ohta, Yasumi; Noda, Toshihiko; Tokuda, Takashi; Ishikawa, Yasuyuki; Ohta, Jun
2016-01-01
To better understand the brain function based on neural activity, a minimally invasive analysis technology in a freely moving animal is necessary. Such technology would provide new knowledge in neuroscience and contribute to regenerative medical techniques and prosthetics care. An application that combines optogenetics for voluntarily stimulating nerves, imaging to visualize neural activity, and a wearable micro-instrument for implantation into the brain could meet the abovementioned demand. To this end, a micro-device that can be applied to the brain less invasively and a system for controlling the device has been newly developed in this study. Since the novel implantable device has dual LEDs and a CMOS image sensor, photostimulation and fluorescence imaging can be performed simultaneously. The device enables bidirectional communication with the brain by means of light. In the present study, the device was evaluated in an in vitro experiment using a new on-chip 3D neuroculture with an extracellular matrix gel and an in vivo experiment involving regenerative medical transplantation and gene delivery to the brain by using both photosensitive channel and fluorescent Ca2+ indicator. The device succeeded in activating cells locally by selective photostimulation, and the physiological Ca2+ dynamics of neural cells were visualized simultaneously by fluorescence imaging. PMID:26878910
-
NASA Astrophysics Data System (ADS)
Kobayashi, Takuma; Haruta, Makito; Sasagawa, Kiyotaka; Matsumata, Miho; Eizumi, Kawori; Kitsumoto, Chikara; Motoyama, Mayumi; Maezawa, Yasuyo; Ohta, Yasumi; Noda, Toshihiko; Tokuda, Takashi; Ishikawa, Yasuyuki; Ohta, Jun
2016-02-01
To better understand the brain function based on neural activity, a minimally invasive analysis technology in a freely moving animal is necessary. Such technology would provide new knowledge in neuroscience and contribute to regenerative medical techniques and prosthetics care. An application that combines optogenetics for voluntarily stimulating nerves, imaging to visualize neural activity, and a wearable micro-instrument for implantation into the brain could meet the abovementioned demand. To this end, a micro-device that can be applied to the brain less invasively and a system for controlling the device has been newly developed in this study. Since the novel implantable device has dual LEDs and a CMOS image sensor, photostimulation and fluorescence imaging can be performed simultaneously. The device enables bidirectional communication with the brain by means of light. In the present study, the device was evaluated in an in vitro experiment using a new on-chip 3D neuroculture with an extracellular matrix gel and an in vivo experiment involving regenerative medical transplantation and gene delivery to the brain by using both photosensitive channel and fluorescent Ca2+ indicator. The device succeeded in activating cells locally by selective photostimulation, and the physiological Ca2+ dynamics of neural cells were visualized simultaneously by fluorescence imaging.
-
Hutka, Stefanie; Bidelman, Gavin M; Moreno, Sylvain
2013-12-30
There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain's processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer.
-
Neural basis of exertional fatigue in the heat: A review of magnetic resonance imaging methods.
Tan, X R; Low, I C C; Stephenson, M C; Soong, T W; Lee, J K W
2018-03-01
The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
-
Detecting switching and intermittent causalities in time series
NASA Astrophysics Data System (ADS)
Zanin, Massimiliano; Papo, David
2017-04-01
During the last decade, complex network representations have emerged as a powerful instrument for describing the cross-talk between different brain regions both at rest and as subjects are carrying out cognitive tasks, in healthy brains and neurological pathologies. The transient nature of such cross-talk has nevertheless by and large been neglected, mainly due to the inherent limitations of some metrics, e.g., causality ones, which require a long time series in order to yield statistically significant results. Here, we present a methodology to account for intermittent causal coupling in neural activity, based on the identification of non-overlapping windows within the original time series in which the causality is strongest. The result is a less coarse-grained assessment of the time-varying properties of brain interactions, which can be used to create a high temporal resolution time-varying network. We apply the proposed methodology to the analysis of the brain activity of control subjects and alcoholic patients performing an image recognition task. Our results show that short-lived, intermittent, local-scale causality is better at discriminating both groups than global network metrics. These results highlight the importance of the transient nature of brain activity, at least under some pathological conditions.
-
Individual brain structure and modelling predict seizure propagation.
Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K
2017-03-01
See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.
-
MacNabb, Carrie; Schmitt, Lee; Michlin, Michael; Harris, Ilene; Thomas, Larry; Chittendon, David; Ebner, Timothy J; Dubinsky, Janet M
2006-01-01
The Department of Neuroscience at the University of Minnesota and the Science Museum of Minnesota have developed and implemented a successful program for middle school (grades 5-8) science teachers and their students, called Brain Science on the Move. The overall goals have been to bring neuroscience education to underserved schools, excite students about science, improve their understanding of neuroscience, and foster partnerships between scientists and educators. The program includes BrainU, a teacher professional development institute; Explain Your Brain Assembly and Exhibit Stations, multimedia large-group presentation and hands-on activities designed to stimulate student thinking about the brain; Class Activities, in-depth inquiry-based investigations; and Brain Trunks, materials and resources related to class activities. Formal evaluation of the program indicated that teacher neuroscience knowledge, self-confidence, and use of inquiry-based strategies and neuroscience in their classrooms have increased. Participating teachers increased the time spent teaching neuroscience and devoted more time to "inquiry-based" teaching versus "lecture-based teaching." Teachers appreciated in-depth discussions of pedagogy and science and opportunities for collegial interactions with world-class researchers. Student interest in the brain and in science increased. Since attending BrainU, participating teachers have reported increased enthusiasm about teaching and have become local neuroscience experts within their school communities.
-
MacNabb, Carrie; Schmitt, Lee; Michlin, Michael; Harris, Ilene; Thomas, Larry; Chittendon, David; Ebner, Timothy J.
2006-01-01
The Department of Neuroscience at the University of Minnesota and the Science Museum of Minnesota have developed and implemented a successful program for middle school (grades 5–8) science teachers and their students, called Brain Science on the Move. The overall goals have been to bring neuroscience education to underserved schools, excite students about science, improve their understanding of neuroscience, and foster partnerships between scientists and educators. The program includes BrainU, a teacher professional development institute; Explain Your Brain Assembly and Exhibit Stations, multimedia large-group presentation and hands-on activities designed to stimulate student thinking about the brain; Class Activities, in-depth inquiry-based investigations; and Brain Trunks, materials and resources related to class activities. Formal evaluation of the program indicated that teacher neuroscience knowledge, self-confidence, and use of inquiry-based strategies and neuroscience in their classrooms have increased. Participating teachers increased the time spent teaching neuroscience and devoted more time to “inquiry-based” teaching versus “lecture-based teaching.” Teachers appreciated in-depth discussions of pedagogy and science and opportunities for collegial interactions with world-class researchers. Student interest in the brain and in science increased. Since attending BrainU, participating teachers have reported increased enthusiasm about teaching and have become local neuroscience experts within their school communities. PMID:17012205
-
Resting-state functional brain connectivity: lessons from functional near-infrared spectroscopy.
Niu, Haijing; He, Yong
2014-04-01
Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area of interest and is currently attracting considerable attention as a new imaging tool for the study of resting-state brain function. Using variations in hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency spontaneous neural activity, combining the advantages of portability, low-cost, high temporal sampling rate and less physical burden to participants. The temporal synchronization of spontaneous neuronal activity in anatomically separated regions is referred to as resting-state functional connectivity (RSFC). In the past several years, an increasing body of R-fNIRS RSFC studies has led to many important findings about functional integration among local or whole-brain regions by measuring inter-regional temporal synchronization. Here, we summarize recent advances made in the R-fNIRS RSFC methodologies, from the detection of RSFC (e.g., seed-based correlation analysis, independent component analysis, whole-brain correlation analysis, and graph-theoretical topological analysis), to the assessment of RSFC performance (e.g., reliability, repeatability, and validity), to the application of RSFC in studying normal development and brain disorders. The literature reviewed here suggests that RSFC analyses based on R-fNIRS data are valid and reliable for the study of brain function in healthy and diseased populations, thus providing a promising imaging tool for cognitive science and clinics.
-
Mapping the information flow from one brain to another during gestural communication.
Schippers, Marleen B; Roebroeck, Alard; Renken, Remco; Nanetti, Luca; Keysers, Christian
2010-05-18
Both the putative mirror neuron system (pMNS) and the ventral medial prefrontal cortex (vmPFC) are deemed important for social interaction: the pMNS because it supposedly "resonates" with the actions of others, the vmPFC because it is involved in mentalizing. Strictly speaking, the resonance property of the pMNS has never been investigated. Classical functional MRI experiments have only investigated whether pMNS regions augment their activity when an action is seen or executed. Resonance, however, entails more than only "going on and off together". Activity in the pMNS of an observer should continuously follow the more subtle changes over time in activity of the pMNS of the actor. Here we directly explore whether such resonance indeed occurs during continuous streams of actions. We let participants play the game of charades while we measured brain activity of both gesturer and guesser. We then applied a method to localize directed influences between the brains of the participants: between-brain Granger-causality mapping. Results show that a guesser's brain activity in regions involved in mentalizing and mirroring echoes the temporal structure of a gesturer's brain activity. This provides evidence for resonance theories and indicates a fine-grained temporal interplay between regions involved in motor planning and regions involved in thinking about the mental states of others. Furthermore, this method enables experiments to be more ecologically valid by providing the opportunity to leave social interaction unconstrained. This, in turn, would allow us to tap into the neural substrates of social deficits such as autism spectrum disorder.
-
Brain mapping after prolonged cycling and during recovery in the heat.
De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain
2013-11-01
The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.
-
Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R
2016-03-01
Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Mulik, Rohit S.; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R.
2016-01-01
Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2× more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. PMID:26790145
-
Xia, Likun; Li, Shumei; Wang, Tianyue; Guo, Yaping; Meng, Lihong; Feng, Yunping; Cui, Yu; Wang, Fan; Ma, Jian; Jiang, Guihua
2017-01-01
Objective We aimed to examine how spontaneous brain activity might be related to the pathophysiology of generalized anxiety disorder (GAD). Patients and methods Using resting-state functional MRI, we examined spontaneous regional brain activity in 31 GAD patients (mean age, 36.87±9.16 years) and 36 healthy control participants (mean age, 39.53±8.83 years) matched for age, education, and sex from December 2014 to October 2015. We performed a two-sample t-test on the voxel-based analysis of the regional homogeneity (ReHo) maps. We used Pearson correlation analysis to compare scores from the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, State–Trait Anxiety Scale-Trait Scale, and mean ReHo values. Results We found abnormal spontaneous activity in multiple regions of brain in GAD patients, especially in the sensorimotor cortex and emotional regions. GAD patients showed decreased ReHo values in the right orbital middle frontal gyrus, left anterior cingulate cortex, right middle frontal gyrus, and bilateral supplementary motor areas, with increased ReHo values in the left middle temporal gyrus, left superior temporal gyrus, and right superior occipital gyrus. The ReHo value of the left middle temporal gyrus correlated positively with the Hamilton Anxiety Rating Scale scores. Conclusion These results suggest that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of GAD. PMID:28790831
-
Shulman, Robert G; Hyder, Fahmeed; Rothman, Douglas L
2014-01-01
Functional neuroimaging measures quantitative changes in neurophysiological parameters coupled to neuronal activity during observable behavior. These results have usually been interpreted by assuming that mental causation of behavior arises from the simultaneous actions of distinct psychological mechanisms or modules. However, reproducible localization of these modules in the brain using functional magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging has been elusive other than for sensory systems. In this paper, we show that neuroenergetic studies using PET, calibrated functional magnetic resonance imaging (fMRI), 13C magnetic resonance spectroscopy, and electrical recordings do not support the standard approach, which identifies the location of mental modules from changes in brain activity. Of importance in reaching this conclusion is that changes in neuronal activities underlying the fMRI signal are many times smaller than the high ubiquitous, baseline neuronal activity, or energy in resting, awake humans. Furthermore, the incremental signal depends on the baseline activity contradicting theoretical assumptions about linearity and insertion of mental modules. To avoid these problems, while making use of these valuable results, we propose that neuroimaging should be used to identify observable brain activities that are necessary for a person's observable behavior rather than being used to seek hypothesized mental processes. PMID:25160670
-
Qin, Pengmin; Duncan, Niall W; Wiebking, Christine; Gravel, Paul; Lyttelton, Oliver; Hayes, Dave J; Verhaeghe, Jeroen; Kostikov, Alexey; Schirrmacher, Ralf; Reader, Andrew J; Northoff, Georg
2012-01-01
Recent imaging studies have demonstrated that levels of resting γ-aminobutyric acid (GABA) in the visual cortex predict the degree of stimulus-induced activity in the same region. These studies have used the presentation of discrete visual stimulus; the change from closed eyes to open also represents a simple visual stimulus, however, and has been shown to induce changes in local brain activity and in functional connectivity between regions. We thus aimed to investigate the role of the GABA system, specifically GABA(A) receptors, in the changes in brain activity between the eyes closed (EC) and eyes open (EO) state in order to provide detail at the receptor level to complement previous studies of GABA concentrations. We conducted an fMRI study involving two different modes of the change from EC to EO: an EO and EC block design, allowing the modeling of the haemodynamic response, followed by longer periods of EC and EO to allow the measuring of functional connectivity. The same subjects also underwent [(18)F]Flumazenil PET to measure GABA(A) receptor binding potentials. It was demonstrated that the local-to-global ratio of GABA(A) receptor binding potential in the visual cortex predicted the degree of changes in neural activity from EC to EO. This same relationship was also shown in the auditory cortex. Furthermore, the local-to-global ratio of GABA(A) receptor binding potential in the visual cortex also predicted the change in functional connectivity between the visual and auditory cortex from EC to EO. These findings contribute to our understanding of the role of GABA(A) receptors in stimulus-induced neural activity in local regions and in inter-regional functional connectivity.
-
Toth, Marton; Faludi, Bela; Wackermann, Jiri; Czopf, Jozsef; Kondakor, Istvan
2009-11-01
EEG background activity of patients with obstructive sleep apnea syndrome (OSAS, N = 25) was compared to that of normal controls (N = 14) to reflect alterations of brain electrical activity caused by chronic intermittent hypoxia in OSAS. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Comparing patients to controls, lower Omega complexity was found globally and in the right hemisphere. Using LORETA, an increased medium frequency activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex. These findings indicate that alterations caused by chronic hypoxia in brain electrical activity in regions associated with influencing emotional regulation, long-term memory and the default mode network. Global synchronization (lower Omega complexity) may indicate a significantly reduced number of relatively independent, parallel neural processes due to chronic global hypoxic state in apneic patients as well as over the right hemisphere.
-
Use of 64-channel electroencephalography to study neural otolith-evoked responses.
McNerney, Kathleen M; Lockwood, Alan H; Coad, Mary Lou; Wack, David S; Burkard, Robert F
2011-03-01
The vestibular evoked myogenic potential (VEMP) is a myogenic response that can be used clinically to evaluate the function of the saccule. However, to date, little is known about the thalamo-cortical representation of saccular activation. It is important to understand all aspects of the VEMP, as this test is currently used clinically in the evaluation of saccular function. To identify the areas of the brain that are activated in response to stimuli used clinically to evoke the VEMP. Electroencephalography (EEG) recordings combined with current density analyses were used to identify the areas of the brain that are activated in response to stimuli presented above VEMP threshold (500 Hz, 120 dB peak SPL [pSPL] tone bursts), as compared to stimuli presented below VEMP threshold (90 dB pSPL, 500 Hz tone bursts). Ten subjects without any history of balance or hearing impairment participated in the study. The neural otolith-evoked responses (NOERs) recorded in response to stimuli presented below VEMP threshold were absent or smaller than NOERs that were recorded in response to stimuli presented above VEMP threshold. Subsequent analyses with source localization techniques, followed by statistical analysis with SPM5 (Statistical Parametric Mapping), revealed several areas that were activated in response to the 120 dB pSPL tone bursts. These areas included the primary visual cortex, the precuneus, the precentral gyrus, the medial temporal gyrus, and the superior temporal gyrus. The present study found a number of specific brain areas that may be activated by otolith stimulation. Given the findings and source localization techniques (which required limited input from the investigator as to where the sources are believed to be located in the brain) used in the present study as well as the similarity in findings between studies employing galvanic stimuli, fMRI (functional magnetic resonance imaging), and scalp-recorded potentials in response to VEMP-eliciting stimuli, our study provides additional evidence that these brain regions are activated in response to stimuli that can be used clinically to evoke the VEMP. American Academy of Audiology.
-
Hauswald, Anne; Übelacker, Teresa; Leske, Sabine; Weisz, Nathan
2015-01-01
Experienced meditators are able to voluntarily modulate their state of consciousness and attention. In the present study, we took advantage of this ability and studied brain activity related to the shift of mental state. Electrophysiological activity, i.e. EEG, was recorded from 11 subjects with varying degrees of meditation experience during Zen meditation (a form of open monitoring meditation) and during non-meditation rest. On a behavioral level, mindfulness scores were assessed using the Mindfulness Attention and Awareness Scale (MAAS). Analysis of EEG source power revealed the so far unreported finding that MAAS scores significantly correlated with gamma power (30–250 Hz), particularly high-frequency gamma (100–245 Hz), during meditation. High levels of mindfulness were related to increased high-frequency gamma, for example, in the cingulate cortex and somatosensory cortices. Further, we analyzed the relationship between connectivity during meditation and self-reported mindfulness (MAAS). We found a correlation between graph measures in the 160–170 Hz range and MAAS scores. Higher levels of mindfulness were related to lower small worldedness as well as global and local clustering in paracentral, insular, and thalamic regions during meditation. In sum, the present study shows significant relationships of mindfulness and brain activity during meditation indicated by measures of oscillatory power and graph theoretical measures. The most prominent effects occur in brain structures crucially involved in processes of awareness and attention, which also show structural changes in short- and long-term meditators, suggesting continuative alterations in the meditating brain. Overall, our study reveals strong changes in ongoing oscillatory activity as well as connectivity patterns that appear to be sensitive to the psychological state changes induced by Zen meditation. PMID:25562827
-
Hauswald, Anne; Übelacker, Teresa; Leske, Sabine; Weisz, Nathan
2015-03-01
Experienced meditators are able to voluntarily modulate their state of consciousness and attention. In the present study, we took advantage of this ability and studied brain activity related to the shift of mental state. Electrophysiological activity, i.e. EEG, was recorded from 11 subjects with varying degrees of meditation experience during Zen meditation (a form of open monitoring meditation) and during non-meditation rest. On a behavioral level, mindfulness scores were assessed using the Mindfulness Attention and Awareness Scale (MAAS). Analysis of EEG source power revealed the so far unreported finding that MAAS scores significantly correlated with gamma power (30-250Hz), particularly high-frequency gamma (100-245Hz), during meditation. High levels of mindfulness were related to increased high-frequency gamma, for example, in the cingulate cortex and somatosensory cortices. Further, we analyzed the relationship between connectivity during meditation and self-reported mindfulness (MAAS). We found a correlation between graph measures in the 160-170Hz range and MAAS scores. Higher levels of mindfulness were related to lower small worldedness as well as global and local clustering in paracentral, insular, and thalamic regions during meditation. In sum, the present study shows significant relationships of mindfulness and brain activity during meditation indicated by measures of oscillatory power and graph theoretical measures. The most prominent effects occur in brain structures crucially involved in processes of awareness and attention, which also show structural changes in short- and long-term meditators, suggesting continuative alterations in the meditating brain. Overall, our study reveals strong changes in ongoing oscillatory activity as well as connectivity patterns that appear to be sensitive to the psychological state changes induced by Zen meditation. Copyright © 2015. Published by Elsevier Inc.
-
Saito, Mitsuo; Chakraborty, Goutam; Shah, Relish; Mao, Rui-Fen; Kumar, Asok; Yang, Dun-Sheng; Dobrenis, Kostantin; Saito, Mariko
2012-05-01
GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase 3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c release and caspase 3 activation in the 7-day-old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
-
Whitmore, Nathan W; Lin, Shih-Chieh
2016-05-15
Local field potentials (LFPs) are commonly thought to reflect the aggregate dynamics in local neural circuits around recording electrodes. However, we show that when LFPs are recorded in awake behaving animals against a distal reference on the skull as commonly practiced, LFPs are significantly contaminated by non-local and non-neural sources arising from the reference electrode and from movement-related noise. In a data set with simultaneously recorded LFPs and electroencephalograms (EEGs) across multiple brain regions while rats perform an auditory oddball task, we used independent component analysis (ICA) to identify signals arising from electrical reference and from volume-conducted noise based on their distributed spatial pattern across multiple electrodes and distinct power spectral features. These sources of distal electrical signals collectively accounted for 23-77% of total variance in unprocessed LFPs, as well as most of the gamma oscillation responses to the target stimulus in EEGs. Gamma oscillation power was concentrated in volume-conducted noise and was tightly coupled with the onset of licking behavior, suggesting a likely origin of muscle activity associated with body movement or orofacial movement. The removal of distal signal contamination also selectively reduced correlations of LFP/EEG signals between distant brain regions but not within the same region. Finally, the removal of contamination from distal electrical signals preserved an event-related potential (ERP) response to auditory stimuli in the frontal cortex and also increased the coupling between the frontal ERP amplitude and neuronal activity in the basal forebrain, supporting the conclusion that removing distal electrical signals unmasked local activity within LFPs. Together, these results highlight the significant contamination of LFPs by distal electrical signals and caution against the straightforward interpretation of unprocessed LFPs. Our results provide a principled approach to identify and remove such contamination to unmask local LFPs. Published by Elsevier Inc.
-
Whitmore, Nathan W.; Lin, Shih-Chieh
2016-01-01
Local field potentials (LFPs) are commonly thought to reflect the aggregate dynamics in local neural circuits around recording electrodes. However, we show that when LFPs are recorded in awake behaving animals against a distal reference on the skull as commonly practiced, LFPs are significantly contaminated by non-local and non-neural sources arising from the reference electrode and from movement-related noise. In a data set with simultaneously recorded LFPs and electroencephalograms (EEGs) across multiple brain regions while rats perform an auditory oddball task, we used independent component analysis (ICA) to identify signals arising from electrical reference and from volume-conducted noise based on their distributed spatial pattern across multiple electrodes and distinct power spectral features. These sources of distal electrical signals collectively accounted for 23–77% of total variance in unprocessed LFPs, as well as most of the gamma oscillation responses to the target stimulus in EEGs. Gamma oscillation power was concentrated in volume-conducted noise and was tightly coupled with the onset of licking behavior, suggesting a likely origin of muscle activity associated with body movement or orofacial movement. The removal of distal signal contamination also selectively reduced correlations of LFP/EEG signals between distant brain regions but not within the same region. Finally, the removal of contamination from distal electrical signals preserved an event-related potential (ERP) response to auditory stimuli in the frontal cortex and also increased the coupling between the frontal ERP amplitude and neuronal activity in the basal forebrain, supporting the conclusion that removing distal electrical signals unmasked local activity within LFPs. Together, these results highlight the significant contamination of LFPs by distal electrical signals and caution against the straightforward interpretation of unprocessed LFPs. Our results provide a principled approach to identify and remove such contamination to unmask local LFPs. PMID:26899209
-
Brain Slice Staining and Preparation for Three-Dimensional Super-Resolution Microscopy
German, Christopher L.; Gudheti, Manasa V.; Fleckenstein, Annette E.; Jorgensen, Erik M.
2018-01-01
Localization microscopy techniques – such as photoactivation localization microscopy (PALM), fluorescent PALM (FPALM), ground state depletion (GSD), and stochastic optical reconstruction microscopy (STORM) – provide the highest precision for single molecule localization currently available. However, localization microscopy has been largely limited to cell cultures due to the difficulties that arise in imaging thicker tissue sections. Sample fixation and antibody staining, background fluorescence, fluorophore photoinstability, light scattering in thick sections, and sample movement create significant challenges for imaging intact tissue. We have developed a sample preparation and image acquisition protocol to address these challenges in rat brain slices. The sample preparation combined multiple fixation steps, saponin permeabilization, and tissue clarification. Together, these preserve intracellular structures, promote antibody penetration, reduce background fluorescence and light scattering, and allow acquisition of images deep in a 30 μm thick slice. Image acquisition challenges were resolved by overlaying samples with a permeable agarose pad and custom-built stainless steel imaging adapter, and sealing the imaging chamber. This approach kept slices flat, immobile, bathed in imaging buffer, and prevented buffer oxidation during imaging. Using this protocol, we consistently obtained single molecule localizations of synaptic vesicle and active zone proteins in three-dimensions within individual synaptic terminals of the striatum in rat brain slices. These techniques may be easily adapted to the preparation and imaging of other tissues, substantially broadening the application of super-resolution imaging. PMID:28924666
-
2016-01-01
When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574303
-
Explaining how brain stimulation can evoke memories.
Jacobs, Joshua; Lega, Bradley; Anderson, Christopher
2012-03-01
An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.
-
Turner, Robert
2016-10-05
When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Authors.
-
Functional brain connectivity when cooperation fails.
Balconi, Michela; Vanutelli, Maria Elide; Gatti, Laura
2018-06-01
Functional connectivity during cooperative actions is an important topic in social neuroscience that has yet to be answered. Here, we examined the effects of administration of (fictitious) negative social feedback in relation to cooperative capabilities. Cognitive performance and neural activation underlying the execution of joint actions was recorded with functional near-infrared spectroscopy (fNIRS) on prefrontal regions during a task where pairs of participants received negative feedback after their joint action. Performance (error rates (ERs) and response times (RTs)) and intra- and inter-brain connectivity indices were computed, along with the ConIndex (inter-brain/intra-brain connectivity). Finally, correlational measures were considered to assess the relation between these different measures. Results showed that the negative feedback was able to modulate participants' responses for both behavioral and neural components. Cognitive performance was decreased after the feedback. Moreover, decreased inter-brain connectivity and increased intra-brain connectivity was induced by the feedback, whereas the cooperative task pre-feedback condition was able to increase the brain-to-brain coupling, mainly localized within the dorsolateral prefrontal cortex (DLPFC). Finally, the presence of significant correlations between RTs and inter-brain connectivity revealed that ineffective joint action produces the worst cognitive performance and a more 'individual strategy' for brain activity, limiting the inter-brain connectivity. The present study provides a significant contribution to the identification of patterns of intra- and inter-brain functional connectivity when negative social reinforcement is provided in relation to cooperative actions. Copyright © 2018 Elsevier Inc. All rights reserved.
-
An fMRI compatible wrist robotic interface to study brain development in neonates.
Allievi, A G; Melendez-Calderon, A; Arichi, T; Edwards, A D; Burdet, E
2013-06-01
A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant's primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyd, S.K.
1987-01-01
Because arginine vasotocin (AVT) activates male sexual behaviors in the rough-skinned newt (Taricha granulosa), quantitative autoradiography with radiolabeled arginine vasopressin (/sup 3/H-AVP) was used to localize and characterize putative AVT receptors in the brain of this amphibian. Binding of /sup 3/H-AVP to sites within the medial pallium was saturable, specific, reversible, of high affinity and low capacity. These binding sites appear to represent authentic central nervous system receptors for AVT. Furthermore, ligand specificity for the binding sites in this amphibian differs from that reported for AVP binding sites in rat brains. Dense concentrations of specific binding sites were located inmore » the olfactory nerve as it entered the olfactory bulb within the medial pallium, dorsal pallium, and amygdala pars lateralis of the telencephalon, and in the tegmental region of the medulla. Concentrations of binding sites differed significantly among various brain regions. A comparison of male and female newts collected during the breeding season revealed no sexual dimorphism. These areas may represent site(s) of action where AVT elicits sexual behaviors in male T. granulosa.« less
-
The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.
Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino
2017-01-01
Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
-
Bola, R. Aaron; Kiyatkin, Eugene A.
2016-01-01
Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc) strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital, which is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r = 0.99) between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain tissue could be strongly modulated by pharmacological drugs via drug-induced changes in metabolic activity and the tone of cerebral vessels. PMID:26913008
-
Fellner, Marie-Christin; Bäuml, Karl-Heinz T; Hanslmayr, Simon
2013-10-01
Memory crucially depends on the way information is processed during encoding. Differences in processes during encoding not only lead to differences in memory performance but also rely on different brain networks. Although these assumptions are corroborated by several previous fMRI and ERP studies, little is known about how brain oscillations dissociate between different memory encoding tasks. The present study therefore compared encoding related brain oscillatory activity elicited by two very efficient encoding tasks: a typical deep semantic item feature judgment task and a more elaborative survival encoding task. Subjects were asked to judge words either for survival relevance or for animacy, as indicated by a cue presented prior to the item. This allowed dissociating pre-item activity from item-related activity for both tasks. Replicating prior studies, survival processing led to higher recognition performance than semantic processing. Successful encoding in the semantic condition was reflected by a strong decrease in alpha and beta power, whereas successful encoding in the survival condition was related to increased alpha and beta long-range phase synchrony. Moreover, a pre-item subsequent memory effect in theta power was found which did not vary with encoding condition. These results show that measures of local synchrony (power) and global long range-synchrony (phase synchronization) dissociate between memory encoding processes. Whereas semantic encoding was reflected in decreases in local synchrony, increases in global long range synchrony were related to elaborative survival encoding, presumably reflecting the involvement of a more widespread cortical network in this task. Copyright © 2013 Elsevier Inc. All rights reserved.
-
Shulman, Abraham; Goldstein, Barbara
2014-01-01
The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = ± 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient.
-
The Cluster Variation Method: A Primer for Neuroscientists.
Maren, Alianna J
2016-09-30
Effective Brain-Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables , is defined in terms of a single interaction enthalpy parameter ( h ) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found.
-
Neural Correlates of Math Gains Vary Depending on Parental Socioeconomic Status (SES)
Demir-Lira, Özlem Ece; Prado, Jérôme; Booth, James R.
2016-01-01
We used functional magnetic resonance imaging (fMRI) to examine the neural predictors of math development, and asked whether these predictors vary as a function of parental socioeconomic status (SES) in children ranging in age from 8 to 13 years. We independently localized brain regions subserving verbal versus spatial processing in order to characterize relations between activation in these regions during an arithmetic task and long-term change in math skill (up to 3 years). Neural predictors of math gains encompassed brain regions subserving both verbal and spatial processing, but the relation between relative reliance on these regions and math skill growth varied depending on parental SES. Activity in an area of the left inferior frontal gyrus (IFG) identified by the verbal localizer was related to greater growth in math skill at the higher end of the SES continuum, but lesser improvements at the lower end. Activity in an area of the right superior parietal cortex identified by the spatial localizer was related to greater growth in math skill at the lower end of the SES continuum, but lesser improvements at the higher end. Results highlight early neural mechanisms as possible neuromarkers of long-term arithmetic learning and suggest that neural predictors of math gains vary with parental SES. PMID:27378987
-
Hsu, Wei-Lun; Chung, Hui-Wen; Wu, Chih-Yueh; Wu, Huei-Ing; Lee, Yu-Tao; Chen, En-Chan; Fang, Weilun; Chang, Yen-Chung
2015-08-21
Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. By analyzing the metabolic incorporation of azidohomoalanine, a methionine analogue, in newly synthesized proteins, we find that glutamate treatments up-regulate protein translation not only in intact rat cortical neurons in culture but also in the axons emitting from cortical neurons before making synapses with target cells. The process by which glutamate stimulates local translation in axons begins with the binding of glutamate to the ionotropic AMPA receptors and metabotropic glutamate receptor 1 and members of group 2 metabotropic glutamate receptors on the plasma membrane. Subsequently, the activated mammalian target of rapamycin (mTOR) signaling pathway and the rise in Ca(2+), resulting from Ca(2+) influxes through calcium-permeable AMPA receptors, voltage-gated Ca(2+) channels, and transient receptor potential canonical channels, in axons stimulate the local translation machinery. For comparison, the enhancement effects of brain-derived neurotrophic factor (BDNF) on the local protein synthesis in cortical axons were also studied. The results indicate that Ca(2+) influxes via transient receptor potential canonical channels and activated the mTOR pathway in axons also mediate BDNF stimulation to local protein synthesis. However, glutamate- and BDNF-induced enhancements of translation in axons exhibit different kinetics. Moreover, Ca(2+) and mTOR signaling appear to play roles carrying different weights, respectively, in transducing glutamate- and BDNF-induced enhancements of axonal translation. Thus, our results indicate that exposure to transient increases of glutamate and more lasting increases of BDNF would stimulate local protein synthesis in migrating axons en route to their targets in the developing brain. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
-
Hsu, Wei-Lun; Chung, Hui-Wen; Wu, Chih-Yueh; Wu, Huei-Ing; Lee, Yu-Tao; Chen, En-Chan; Fang, Weilun; Chang, Yen-Chung
2015-01-01
Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. By analyzing the metabolic incorporation of azidohomoalanine, a methionine analogue, in newly synthesized proteins, we find that glutamate treatments up-regulate protein translation not only in intact rat cortical neurons in culture but also in the axons emitting from cortical neurons before making synapses with target cells. The process by which glutamate stimulates local translation in axons begins with the binding of glutamate to the ionotropic AMPA receptors and metabotropic glutamate receptor 1 and members of group 2 metabotropic glutamate receptors on the plasma membrane. Subsequently, the activated mammalian target of rapamycin (mTOR) signaling pathway and the rise in Ca2+, resulting from Ca2+ influxes through calcium-permeable AMPA receptors, voltage-gated Ca2+ channels, and transient receptor potential canonical channels, in axons stimulate the local translation machinery. For comparison, the enhancement effects of brain-derived neurotrophic factor (BDNF) on the local protein synthesis in cortical axons were also studied. The results indicate that Ca2+ influxes via transient receptor potential canonical channels and activated the mTOR pathway in axons also mediate BDNF stimulation to local protein synthesis. However, glutamate- and BDNF-induced enhancements of translation in axons exhibit different kinetics. Moreover, Ca2+ and mTOR signaling appear to play roles carrying different weights, respectively, in transducing glutamate- and BDNF-induced enhancements of axonal translation. Thus, our results indicate that exposure to transient increases of glutamate and more lasting increases of BDNF would stimulate local protein synthesis in migrating axons en route to their targets in the developing brain. PMID:26134564
-
A Subspace Pursuit–based Iterative Greedy Hierarchical Solution to the Neuromagnetic Inverse Problem
Babadi, Behtash; Obregon-Henao, Gabriel; Lamus, Camilo; Hämäläinen, Matti S.; Brown, Emery N.; Purdon, Patrick L.
2013-01-01
Magnetoencephalography (MEG) is an important non-invasive method for studying activity within the human brain. Source localization methods can be used to estimate spatiotemporal activity from MEG measurements with high temporal resolution, but the spatial resolution of these estimates is poor due to the ill-posed nature of the MEG inverse problem. Recent developments in source localization methodology have emphasized temporal as well as spatial constraints to improve source localization accuracy, but these methods can be computationally intense. Solutions emphasizing spatial sparsity hold tremendous promise, since the underlying neurophysiological processes generating MEG signals are often sparse in nature, whether in the form of focal sources, or distributed sources representing large-scale functional networks. Recent developments in the theory of compressed sensing (CS) provide a rigorous framework to estimate signals with sparse structure. In particular, a class of CS algorithms referred to as greedy pursuit algorithms can provide both high recovery accuracy and low computational complexity. Greedy pursuit algorithms are difficult to apply directly to the MEG inverse problem because of the high-dimensional structure of the MEG source space and the high spatial correlation in MEG measurements. In this paper, we develop a novel greedy pursuit algorithm for sparse MEG source localization that overcomes these fundamental problems. This algorithm, which we refer to as the Subspace Pursuit-based Iterative Greedy Hierarchical (SPIGH) inverse solution, exhibits very low computational complexity while achieving very high localization accuracy. We evaluate the performance of the proposed algorithm using comprehensive simulations, as well as the analysis of human MEG data during spontaneous brain activity and somatosensory stimuli. These studies reveal substantial performance gains provided by the SPIGH algorithm in terms of computational complexity, localization accuracy, and robustness. PMID:24055554
-
Getter, Nir; Kaplan, Zeev; Todder, Doron
2015-10-01
Electroencephalography source localization neurofeedback, i.e Standardized low-resolution tomography (sLORETA) neurofeedback are non-invasive method for altering region specific brain activity. This is an improvement over traditional neurofeedback which were based on recordings from a single scalp-electrode. We proposed three criteria clusters as a methodological framework to evaluate electroencephalography source localization neurofeedback and present relevant data. Our objective was to evaluate standardized low resolution EEG tomography neurofeedback by examining how training one neuroanatomical area effects the mental rotation task (which is related to the activity of bilateral Parietal regions) and the stop-signal test (which is related to frontal structures). Twelve healthy participants were enrolled in a single session sLORETA neurofeedback protocol. The participants completed both the mental rotation task and the stop-signal test before and after one sLORETA neurofeedback session. During sLORETA neurofeedback sessions participants watched one sitcom episode while the picture quality co-varied with activity in the superior parietal lobule. Participants were rewarded for increasing activity in this region only. Results showed a significant reaction time decrease and an increase in accuracy after sLORETA neurofeedback on the mental rotation task but not after stop signal task. Together with behavioral changes a significant activity increase was found at the left parietal brain after sLORETA neurofeedback compared with baseline. We concluded that activity increase in the parietal region had a specific effect on the mental rotation task. Tasks unrelated to parietal brain activity were unaffected. Therefore, sLORETA neurofeedback could be used as a research, or clinical tool for cognitive disorders. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Solute Carriers in the Blood-Brain Barier: Safety in Abundance.
Nałęcz, Katarzyna A
2017-03-01
Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5, SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the blood-brain barriers has been demonstrated are characterized with a special emphasis put on polarity of transporters localization in a luminal (blood side) versus an abluminal (brain side) membrane.
-
NASA Astrophysics Data System (ADS)
Vergallo, P.; Lay-Ekuakille, A.
2013-08-01
Brain activity can be recorded by means of EEG (Electroencephalogram) electrodes placed on the scalp of the patient. The EEG reflects the activity of groups of neurons located in the head, and the fundamental problem in neurophysiology is the identification of the sources responsible of brain activity, especially if a seizure occurs and in this case it is important to identify it. The studies conducted in order to formalize the relationship between the electromagnetic activity in the head and the recording of the generated external field allow to know pattern of brain activity. The inverse problem, that is given the sampling field at different electrodes the underlying asset must be determined, is more difficult because the problem may not have a unique solution, or the search for the solution is made difficult by a low spatial resolution which may not allow to distinguish between activities involving sources close to each other. Thus, sources of interest may be obscured or not detected and known method in source localization problem as MUSIC (MUltiple SIgnal Classification) could fail. Many advanced source localization techniques achieve a best resolution by exploiting sparsity: if the number of sources is small as a result, the neural power vs. location is sparse. In this work a solution based on the spatial sparsity of the field signal is presented and analyzed to improve MUSIC method. For this purpose, it is necessary to set a priori information of the sparsity in the signal. The problem is formulated and solved using a regularization method as Tikhonov, which calculates a solution that is the better compromise between two cost functions to minimize, one related to the fitting of the data, and another concerning the maintenance of the sparsity of the signal. At the first, the method is tested on simulated EEG signals obtained by the solution of the forward problem. Relatively to the model considered for the head and brain sources, the result obtained allows to have a significant improvement compared to the classical MUSIC method, with a small margin of uncertainty about the exact location of the sources. In fact, the constraints of the spatial sparsity on the signal field allow to concentrate power in the directions of active sources, and consequently it is possible to calculate the position of the sources within the considered volume conductor. Later, the method is tested on the real EEG data too. The result is in accordance with the clinical report even if improvements are necessary to have further accurate estimates of the positions of the sources.
-
Robot-assisted motor activation monitored by time-domain optical brain imaging
NASA Astrophysics Data System (ADS)
Steinkellner, O.; Wabnitz, H.; Schmid, S.; Steingräber, R.; Schmidt, H.; Krüger, J.; Macdonald, R.
2011-07-01
Robot-assisted motor rehabilitation proved to be an effective supplement to conventional hand-to-hand therapy in stroke patients. In order to analyze and understand motor learning and performance during rehabilitation it is desirable to develop a monitor to provide objective measures of the corresponding brain activity at the rehabilitation progress. We used a portable time-domain near-infrared reflectometer to monitor the hemodynamic brain response to distal upper extremity activities. Four healthy volunteers performed two different robot-assisted wrist/forearm movements, flexion-extension and pronation-supination in comparison with an unassisted squeeze ball exercise. A special headgear with four optical measurement positions to include parts of the pre- and postcentral gyrus provided a good overlap with the expected activation areas. Data analysis based on variance of time-of-flight distributions of photons through tissue was chosen to provide a suitable representation of intracerebral signals. In all subjects several of the four detection channels showed a response. In some cases indications were found of differences in localization of the activated areas for the various tasks.
-
Sex differences in the neural representation of pain unpleasantness.
Girard-Tremblay, Lydia; Auclair, Vincent; Daigle, Kathya; Léonard, Guillaume; Whittingstall, Kevin; Goffaux, Philippe
2014-08-01
Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. This article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
-
Grimault, Stephan; Nolden, Sophie; Lefebvre, Christine; Vachon, François; Hyde, Krista; Peretz, Isabelle; Zatorre, Robert; Robitaille, Nicolas; Jolicoeur, Pierre
2014-07-01
We used magnetoencephalography (MEG) to examine brain activity related to the maintenance of non-verbal pitch information in auditory short-term memory (ASTM). We focused on brain activity that increased with the number of items effectively held in memory by the participants during the retention interval of an auditory memory task. We used very simple acoustic materials (i.e., pure tones that varied in pitch) that minimized activation from non-ASTM related systems. MEG revealed neural activity in frontal, temporal, and parietal cortices that increased with a greater number of items effectively held in memory by the participants during the maintenance of pitch representations in ASTM. The present results reinforce the functional role of frontal and temporal cortices in the retention of pitch information in ASTM. This is the first MEG study to provide both fine spatial localization and temporal resolution on the neural mechanisms of non-verbal ASTM for pitch in relation to individual differences in the capacity of ASTM. This research contributes to a comprehensive understanding of the mechanisms mediating the representation and maintenance of basic non-verbal auditory features in the human brain. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Altered Spontaneous Activity in Anisometropic Amblyopia Subjects: Revealed by Resting-State fMRI
Lin, Xiaoming; Ding, Kun; Liu, Yong; Yan, Xiaohe; Song, Shaojie; Jiang, Tianzi
2012-01-01
Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo), a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia. PMID:22937041
-
Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.
Watanabe, T; Morimoto, A; Murakami, N
1987-06-01
We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.
-
Probe-pin device for optical neurotransmitter sensing in the brain
NASA Astrophysics Data System (ADS)
Kim, Min Hyuck; Song, Kyo D.; Yoon, Hargsoon; Park, Yeonjoon; Choi, Sang H.; Lee, Dae-Sung; Shin, Kyu-Sik; Hwang, Hak-In; Lee, Uhn
2015-04-01
Development of an optical neurotransmitter sensing device using nano-plasmonic probes and a micro-spectrometer for real time monitoring of neural signals in the brain is underway. Clinical application of this device technology is to provide autonomous closed-loop feedback control to a deep brain stimulation (DBS) system and enhance the accuracy and efficacy of DBS treatment. By far, we have developed an implantable probe-pin device based on localized field enhancement of surface plasmonic resonance on a nanostructured sensing domain which can amplify neurochemical signals from evoked neural activity in the brain. In this paper, we will introduce the details of design and sensing performance of a proto-typed microspectrometer and nanostructured probing devices for real time measurement of neurotransmitter concentrations.
-
Jiang, Lili; Zuo, Xi-Nian
2015-01-01
Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004
-
Schrot, Rudolph J; Ma, Joyce H; Greco, Claudia M; Arias, Angelo D; Angelastro, James M
2007-11-01
The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.
-
Localization of PPAR isotypes in the adult mouse and human brain
Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron
2016-01-01
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430
-
Localization of PPAR isotypes in the adult mouse and human brain.
Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B; Mayfield, R Dayne; Harris, R Adron
2016-06-10
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.
-
Activity flow over resting-state networks shapes cognitive task activations.
Cole, Michael W; Ito, Takuya; Bassett, Danielle S; Schultz, Douglas H
2016-12-01
Resting-state functional connectivity (FC) has helped reveal the intrinsic network organization of the human brain, yet its relevance to cognitive task activations has been unclear. Uncertainty remains despite evidence that resting-state FC patterns are highly similar to cognitive task activation patterns. Identifying the distributed processes that shape localized cognitive task activations may help reveal why resting-state FC is so strongly related to cognitive task activations. We found that estimating task-evoked activity flow (the spread of activation amplitudes) over resting-state FC networks allowed prediction of cognitive task activations in a large-scale neural network model. Applying this insight to empirical functional MRI data, we found that cognitive task activations can be predicted in held-out brain regions (and held-out individuals) via estimated activity flow over resting-state FC networks. This suggests that task-evoked activity flow over intrinsic networks is a large-scale mechanism explaining the relevance of resting-state FC to cognitive task activations.
-
Activity flow over resting-state networks shapes cognitive task activations
Cole, Michael W.; Ito, Takuya; Bassett, Danielle S.; Schultz, Douglas H.
2016-01-01
Resting-state functional connectivity (FC) has helped reveal the intrinsic network organization of the human brain, yet its relevance to cognitive task activations has been unclear. Uncertainty remains despite evidence that resting-state FC patterns are highly similar to cognitive task activation patterns. Identifying the distributed processes that shape localized cognitive task activations may help reveal why resting-state FC is so strongly related to cognitive task activations. We found that estimating task-evoked activity flow (the spread of activation amplitudes) over resting-state FC networks allows prediction of cognitive task activations in a large-scale neural network model. Applying this insight to empirical functional MRI data, we found that cognitive task activations can be predicted in held-out brain regions (and held-out individuals) via estimated activity flow over resting-state FC networks. This suggests that task-evoked activity flow over intrinsic networks is a large-scale mechanism explaining the relevance of resting-state FC to cognitive task activations. PMID:27723746
-
Localization of Asymmetric Brain Function in Emotion and Depression
Herrington, John D.; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S.; Banich, Marie T.; Webb, Andrew G.; Miller, Gregory A.
2011-01-01
Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used. PMID:20070577
-
Localization of asymmetric brain function in emotion and depression.
Herrington, John D; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S; Banich, Marie T; Webb, Andrew G; Miller, Gregory A
2010-05-01
Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.
-
Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan
2017-09-01
A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p < 0.05). Ischemia-reperfusion-induced renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.
-
Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization.
Faber, Pascal L; Lehmann, Dietrich; Gianotti, Lorena R R; Milz, Patricia; Pascual-Marqui, Roberto D; Held, Marlene; Kochi, Kieko
2015-02-01
Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.
-
Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.
Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, Christian
2015-07-15
Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Cellular Links between Neuronal Activity and Energy Homeostasis.
Shetty, Pavan K; Galeffi, Francesca; Turner, Dennis A
2012-01-01
Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.
-
NASA Astrophysics Data System (ADS)
Maksimenko, Vladimir A.; Lüttjohann, Annika; Makarov, Vladimir V.; Goremyko, Mikhail V.; Koronovskii, Alexey A.; Nedaivozov, Vladimir; Runnova, Anastasia E.; van Luijtelaar, Gilles; Hramov, Alexander E.; Boccaletti, Stefano
2017-07-01
We introduce a practical and computationally not demanding technique for inferring interactions at various microscopic levels between the units of a network from the measurements and the processing of macroscopic signals. Starting from a network model of Kuramoto phase oscillators, which evolve adaptively according to homophilic and homeostatic adaptive principles, we give evidence that the increase of synchronization within groups of nodes (and the corresponding formation of synchronous clusters) causes also the defragmentation of the wavelet energy spectrum of the macroscopic signal. Our methodology is then applied to getting a glance into the microscopic interactions occurring in a neurophysiological system, namely, in the thalamocortical neural network of an epileptic brain of a rat, where the group electrical activity is registered by means of multichannel EEG. We demonstrate that it is possible to infer the degree of interaction between the interconnected regions of the brain during different types of brain activities and to estimate the regions' participation in the generation of the different levels of consciousness.
-
Nashiro, Kaoru; Qin, Shuo; O'Connell, Margaret A; Basak, Chandramallika
2018-05-15
It is well documented that older adults recruit additional brain regions compared to those recruited by younger adults while performing a wide variety of cognitive tasks. However, it is unclear how such age-related over-recruitment interacts with different types of cognitive control, and whether this over-recruitment is compensatory. To test this, we used a multitasking paradigm, which allowed us to examine age-related over-activation associated with three types of cognitive costs (i.e., global switch, local switch, compatibility-switch costs). We found age-related impairments in global switch cost (GSC), evidenced by slower response times for maintaining and coordinating two tasks vs. performing only one task. However, no age-related declines were observed in either local switch cost (LSC), a cognitive cost associated with switching between the two tasks while maintaining two task loads, or compatibility-switch cost (CSC), a cognitive cost associated with incompatible vs. compatible stimulus-response mappings across the two tasks. The fMRI analyses allowed for identification of distinct cognitive cost-sensitive brain regions associated with GSC and LSC. In fronto-parietal GSC and LSC regions, older adults' increased activations were associated with poorer performance (greater costs), whereas a reverse relationship was observed in younger adults. Older adults also recruited additional fronto-parietal brain regions outside the cognitive cost-sensitive areas, which was associated with poorer performance or no behavioral benefits. Our results suggest that older adults exhibit a combination of inefficient activation within cognitive cost-sensitive regions, specifically the GSC and LSC regions, and non-compensatory over-recruitment in age-sensitive regions. Age-related declines in global switching, compared to local switching, was observed earlier in old age at both neural and behavioral levels. Copyright © 2018 Elsevier Inc. All rights reserved.
-
Localizing Pain Matrix and Theory of Mind networks with both verbal and non-verbal stimuli.
Jacoby, Nir; Bruneau, Emile; Koster-Hale, Jorie; Saxe, Rebecca
2016-02-01
Functional localizer tasks allow researchers to identify brain regions in each individual's brain, using a combination of anatomical and functional constraints. In this study, we compare three social cognitive localizer tasks, designed to efficiently identify regions in the "Pain Matrix," recruited in response to a person's physical pain, and the "Theory of Mind network," recruited in response to a person's mental states (i.e. beliefs and emotions). Participants performed three tasks: first, the verbal false-belief stories task; second, a verbal task including stories describing physical pain versus emotional suffering; and third, passively viewing a non-verbal animated movie, which included segments depicting physical pain and beliefs and emotions. All three localizers were efficient in identifying replicable, stable networks in individual subjects. The consistency across tasks makes all three tasks viable localizers. Nevertheless, there were small reliable differences in the location of the regions and the pattern of activity within regions, hinting at more specific representations. The new localizers go beyond those currently available: first, they simultaneously identify two functional networks with no additional scan time, and second, the non-verbal task extends the populations in whom functional localizers can be applied. These localizers will be made publicly available. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Disturbed temporal dynamics of brain synchronization in vision loss.
Bola, Michał; Gall, Carolin; Sabel, Bernhard A
2015-06-01
Damage along the visual pathway prevents bottom-up visual input from reaching further processing stages and consequently leads to loss of vision. But perception is not a simple bottom-up process - rather it emerges from activity of widespread cortical networks which coordinate visual processing in space and time. Here we set out to study how vision loss affects activity of brain visual networks and how networks' activity is related to perception. Specifically, we focused on studying temporal patterns of brain activity. To this end, resting-state eyes-closed EEG was recorded from partially blind patients suffering from chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13). Amplitude (power) of oscillatory activity and phase locking value (PLV) were used as measures of local and distant synchronization, respectively. Synchronization time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and analyzed with three measures of temporal patterns: (i) length of synchronized-/desynchronized-periods, (ii) Higuchi Fractal Dimension (HFD), and (iii) Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less complex, more random and noise-like temporal dynamics of high-alpha band activity. More random temporal patterns were associated with worse performance in static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We conclude that disturbed temporal patterns of neural synchronization in vision loss patients indicate disrupted communication within brain visual networks caused by prolonged deafferentation. We propose that because the state of brain networks is essential for normal perception, impaired brain synchronization in patients with vision loss might aggravate the functional consequences of reduced visual input. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Plasticity of brain wave network interactions and evolution across physiologic states
Liu, Kang K. L.; Bartsch, Ronny P.; Lin, Aijing; Mantegna, Rosario N.; Ivanov, Plamen Ch.
2015-01-01
Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of network connectivity and link strength, while at the same time each frequency-specific network is characterized by a different signature pattern of sleep-stage stratification, reflecting a remarkable flexibility in response to change in physiologic state. These new aspects of neural plasticity demonstrate that in addition to dominant brain waves, the network of brain wave interactions is a previously unrecognized hallmark of physiologic state and function. PMID:26578891
-
Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria.
Villa, Roberto Federico; Ferrari, Federica; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio
2016-08-25
Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
-
Dajani, Dina R.; Uddin, Lucina Q.
2015-01-01
Lay Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with ASD. Here we investigated the development of local connectivity across three age cohorts of individuals with ASD and typically developing (TD) individuals. We find that in typical development, children exhibit high levels of local connectivity across the brain, while adolescents exhibit lower levels of local connectivity, similar to adult levels. On the other hand, children with ASD exhibit marginally lower local connectivity than TD children, and adolescents and adults with ASD exhibit levels of local connectivity comparable to that observed in neurotypical individuals. During all developmental stages -- childhood, adolescence, and adulthood -- individuals with ASD exhibited lower local connectivity in brain regions involved in sensory processing and higher local connectivity in brain regions involved in complex information processing. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. Thus we demonstrate that local connectivity is disrupted in autism across development, with the most pronounced differences occurring in childhood. Scientific Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel’s timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in childhood. Developmental changes in ReHo do not mirror findings from fMRI studies of long-range connectivity in ASD, pointing to a need for more nuanced accounts of brain connectivity alterations in the disorder. PMID:26058882
-
The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke
Falcon, Maria Inez; Riley, Jeffrey D.; Jirsa, Viktor; McIntosh, Anthony R.; Shereen, Ahmed D.; Chen, E. Elinor; Solodkin, Ana
2015-01-01
There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual’s brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P = 0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic interventions. PMID:26579071
-
Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher
2010-06-01
MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.
-
Computationally optimized ECoG stimulation with local safety constraints.
Guler, Seyhmus; Dannhauer, Moritz; Roig-Solvas, Biel; Gkogkidis, Alexis; Macleod, Rob; Ball, Tonio; Ojemann, Jeffrey G; Brooks, Dana H
2018-06-01
Direct stimulation of the cortical surface is used clinically for cortical mapping and modulation of local activity. Future applications of cortical modulation and brain-computer interfaces may also use cortical stimulation methods. One common method to deliver current is through electrocorticography (ECoG) stimulation in which a dense array of electrodes are placed subdurally or epidurally to stimulate the cortex. However, proximity to cortical tissue limits the amount of current that can be delivered safely. It may be desirable to deliver higher current to a specific local region of interest (ROI) while limiting current to other local areas more stringently than is guaranteed by global safety limits. Two commonly used global safety constraints bound the total injected current and individual electrode currents. However, these two sets of constraints may not be sufficient to prevent high current density locally (hot-spots). In this work, we propose an efficient approach that prevents current density hot-spots in the entire brain while optimizing ECoG stimulus patterns for targeted stimulation. Specifically, we maximize the current along a particular desired directional field in the ROI while respecting three safety constraints: one on the total injected current, one on individual electrode currents, and the third on the local current density magnitude in the brain. This third set of constraints creates a computational barrier due to the huge number of constraints needed to bound the current density at every point in the entire brain. We overcome this barrier by adopting an efficient two-step approach. In the first step, the proposed method identifies the safe brain region, which cannot contain any hot-spots solely based on the global bounds on total injected current and individual electrode currents. In the second step, the proposed algorithm iteratively adjusts the stimulus pattern to arrive at a solution that exhibits no hot-spots in the remaining brain. We report on simulations on a realistic finite element (FE) head model with five anatomical ROIs and two desired directional fields. We also report on the effect of ROI depth and desired directional field on the focality of the stimulation. Finally, we provide an analysis of optimization runtime as a function of different safety and modeling parameters. Our results suggest that optimized stimulus patterns tend to differ from those used in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.
-
Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation.
Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A
2017-02-15
Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.
-
Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.
2012-01-01
Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. PMID:23284276
-
Dynamic Neural State Identification in Deep Brain Local Field Potentials of Neuropathic Pain.
Luo, Huichun; Huang, Yongzhi; Du, Xueying; Zhang, Yunpeng; Green, Alexander L; Aziz, Tipu Z; Wang, Shouyan
2018-01-01
In neuropathic pain, the neurophysiological and neuropathological function of the ventro-posterolateral nucleus of the thalamus (VPL) and the periventricular gray/periaqueductal gray area (PVAG) involves multiple frequency oscillations. Moreover, oscillations related to pain perception and modulation change dynamically over time. Fluctuations in these neural oscillations reflect the dynamic neural states of the nucleus. In this study, an approach to classifying the synchronization level was developed to dynamically identify the neural states. An oscillation extraction model based on windowed wavelet packet transform was designed to characterize the activity level of oscillations. The wavelet packet coefficients sparsely represented the activity level of theta and alpha oscillations in local field potentials (LFPs). Then, a state discrimination model was designed to calculate an adaptive threshold to determine the activity level of oscillations. Finally, the neural state was represented by the activity levels of both theta and alpha oscillations. The relationship between neural states and pain relief was further evaluated. The performance of the state identification approach achieved sensitivity and specificity beyond 80% in simulation signals. Neural states of the PVAG and VPL were dynamically identified from LFPs of neuropathic pain patients. The occurrence of neural states based on theta and alpha oscillations were correlated to the degree of pain relief by deep brain stimulation. In the PVAG LFPs, the occurrence of the state with high activity levels of theta oscillations independent of alpha and the state with low-level alpha and high-level theta oscillations were significantly correlated with pain relief by deep brain stimulation. This study provides a reliable approach to identifying the dynamic neural states in LFPs with a low signal-to-noise ratio by using sparse representation based on wavelet packet transform. Furthermore, it may advance closed-loop deep brain stimulation based on neural states integrating multiple neural oscillations.
-
Dynamic Neural State Identification in Deep Brain Local Field Potentials of Neuropathic Pain
Luo, Huichun; Huang, Yongzhi; Du, Xueying; Zhang, Yunpeng; Green, Alexander L.; Aziz, Tipu Z.; Wang, Shouyan
2018-01-01
In neuropathic pain, the neurophysiological and neuropathological function of the ventro-posterolateral nucleus of the thalamus (VPL) and the periventricular gray/periaqueductal gray area (PVAG) involves multiple frequency oscillations. Moreover, oscillations related to pain perception and modulation change dynamically over time. Fluctuations in these neural oscillations reflect the dynamic neural states of the nucleus. In this study, an approach to classifying the synchronization level was developed to dynamically identify the neural states. An oscillation extraction model based on windowed wavelet packet transform was designed to characterize the activity level of oscillations. The wavelet packet coefficients sparsely represented the activity level of theta and alpha oscillations in local field potentials (LFPs). Then, a state discrimination model was designed to calculate an adaptive threshold to determine the activity level of oscillations. Finally, the neural state was represented by the activity levels of both theta and alpha oscillations. The relationship between neural states and pain relief was further evaluated. The performance of the state identification approach achieved sensitivity and specificity beyond 80% in simulation signals. Neural states of the PVAG and VPL were dynamically identified from LFPs of neuropathic pain patients. The occurrence of neural states based on theta and alpha oscillations were correlated to the degree of pain relief by deep brain stimulation. In the PVAG LFPs, the occurrence of the state with high activity levels of theta oscillations independent of alpha and the state with low-level alpha and high-level theta oscillations were significantly correlated with pain relief by deep brain stimulation. This study provides a reliable approach to identifying the dynamic neural states in LFPs with a low signal-to-noise ratio by using sparse representation based on wavelet packet transform. Furthermore, it may advance closed-loop deep brain stimulation based on neural states integrating multiple neural oscillations. PMID:29695951
-
Hutka, Stefanie; Bidelman, Gavin M.; Moreno, Sylvain
2013-01-01
There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain’s processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer. PMID:24454295
-
Hellyer, Peter John; Clopath, Claudia; Kehagia, Angie A; Turkheimer, Federico E; Leech, Robert
2017-08-01
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we describe a simple model of spontaneous neural dynamics that controls an agent moving in a simple virtual environment. These dynamics generate interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics demonstrating the need for homeostatic mechanisms. We investigate roles for homeostatic plasticity both locally (local inhibition adjusting to balance excitatory input) as well as more globally (regional "task negative" activity that compensates for "task positive", sensory input in another region) balancing neural activity and leading to more stable behavior (trajectories through the environment). Our results suggest complementary functional roles for both local and macroscale mechanisms in maintaining neural and behavioral dynamics and a novel functional role for macroscopic "task-negative" patterns of activity (e.g., the default mode network).
-
GDNF family receptor α-1 in the catfish: Possible implication to brain dopaminergic activity.
Mamta, Sajwan-Khatri; Senthilkumaran, Balasubramanian
2018-05-31
Glial cell line-derived neurotrophic factor (GDNF)is a potent trophic factor that preferentially binds to GDNF family receptor α-1 (GFRα-1)by regulating dopaminergic (DA-ergic) neuronsin brain. Present study aimed to evaluate the significance of GFRα-1 expression during early brain development in catfish. Initially, the full-length cDNA of GFRα-1 was cloned from adult brain which showed high homology with other vertebrate counterparts. Quantitative PCR analysis of tissue distribution revealed ubiquitous expression of GFRα-1 in the tissues analyzed with high levels in female brain and ovary. Significant high expression was evident in brain at 75 and 100 days post hatch females than the respective age-match males. Expression of GFRα-1 was high in brain during the spawning phase when compared to other reproductive phases. Localization of GFRα-1 revealed its presence in preoptic area-hypothalamus which correlated well with the expression profile in discrete areas of brain in adult catfish. Transient silencing of GFRα-1through siRNA lowered expression levels of GFRα-1, which further down regulated the expression of certain brain-specific genes. Expression of GFRα-1 in brain declined significantly upon treatment with the 1-methyl-1,2,3,6-tetrahydropyridinecausing neurodegeneration which further correlated with catecholamines (CA), L-3,4-dihydroxyphenylalanine, DA and norepinephrine levels. Taken together, GFRα-1 plausibly entrains gonadotropin-releasing hormone and gonadotropin axiseither directly or indirectly, at least by partially targeting CA-ergic activity. Copyright © 2018 Elsevier Inc. All rights reserved.
-
Solis, Ernesto; Cameron-Burr, Keaton T; Shaham, Yavin; Kiyatkin, Eugene A
2017-01-01
Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100-200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO 2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity.
-
Diurnal alterations of brain electrical activity in healthy adults: a LORETA study.
Toth, Marton; Kiss, Attila; Kosztolanyi, Peter; Kondakor, Istvan
2007-01-01
EEG background activity was investigated by low resolution brain electromagnetic tomography (LORETA) to test the diurnal alterations of brain electrical activity in healthy adults. Fourteen right-handed healthy male postgraduate medical students were examined four times (8 a.m., 2 p.m., 8 p.m. and next day 2 p.m.). LORETA was computed to localize generators of EEG frequency components. Comparing the EEG activity between 2 p.m. and 8 a.m., increased activity was seen (1) in theta band (6.5-8 Hz) in the left prefrontal, bilateral mesial frontal and anterior cingulate cortex; (2) in alpha2 band (10.5-12 Hz) in the bilateral precuneus and posterior parietal cortex as well as in the right temporo-occipital cortex; (3) in beta1-2-3 band (12.5-30 Hz) in the right hippocampus and parieto-occipital cortex, left frontal and bilateral cingulate cortex. Comparing the brain activity between 8 p.m. and 8 a.m., (1) midline theta activity disappeared; (2) increased alpha2 band activity was seen in the left hemisphere (including the left hippocampus); and (3) increased beta bands activity was found over almost the whole cortex (including both of hippocampi) with the exception of left temporo-occipital region. There were no significant changes between the background activities of 2 p.m. and next day 2 p.m. Characteristic distribution of increased activity of cortex (no change in delta band, and massive changes in the upper frequency bands) may mirror increasing activation of reticular formation and thus evoked thalamocortical feedback mechanisms as a sign of maintenance of arousal.
-
Niwińska, Anna
2016-10-01
The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.
-
fMRI evidence for areas that process surface gloss in the human visual cortex
Sun, Hua-Chun; Ban, Hiroshi; Di Luca, Massimiliano; Welchman, Andrew E.
2015-01-01
Surface gloss is an important cue to the material properties of objects. Recent progress in the study of macaque’s brain has increased our understating of the areas involved in processing information about gloss, however the homologies with the human brain are not yet fully understood. Here we used human functional magnetic resonance imaging (fMRI) measurements to localize brain areas preferentially responding to glossy objects. We measured cortical activity for thirty-two rendered three-dimensional objects that had either Lambertian or specular surface properties. To control for differences in image structure, we overlaid a grid on the images and scrambled its cells. We found activations related to gloss in the posterior fusiform sulcus (pFs) and in area V3B/KO. Subsequent analysis with Granger causality mapping indicated that V3B/KO processes gloss information differently than pFs. Our results identify a small network of mid-level visual areas whose activity may be important in supporting the perception of surface gloss. PMID:25490434
-
Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism.
Cai, Bin; Li, Wenjun; Mao, XiaoOu; Winters, Ali; Ryou, Myoung-Gwi; Liu, Ran; Greenberg, David A; Wang, Ning; Jin, Kunlin; Yang, Shao-Hua
2016-03-01
Neuroglobin (Ngb) is a recently discovered globin with preferential localization to neurons. Growing evidence indicates that Ngb has distinct physiological functions separate from the oxygen storage and transport roles of other globins, such as hemoglobin and myoglobin. We found increased ATP production and decreased glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT-22), in parallel with inhibition of AMP-activated protein kinase (AMPK) signaling and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also inhibited in the brain and heart from Ngb-overexpressing transgenic mice. Although Ngb overexpression did not change glycogen content in whole brain, glycogen synthase was activated in cortical neurons of Ngb-overexpressing mouse brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen content was increased in hearts derived from Ngb-overexpressing mice. These findings suggest that Ngb functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling.
-
Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro
2015-01-01
Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB. PMID:25828099
-
Liu, Hesheng; Gao, Xiaorong; Schimpf, Paul H; Yang, Fusheng; Gao, Shangkai
2004-10-01
Estimation of intracranial electric activity from the scalp electroencephalogram (EEG) requires a solution to the EEG inverse problem, which is known as an ill-conditioned problem. In order to yield a unique solution, weighted minimum norm least square (MNLS) inverse methods are generally used. This paper proposes a recursive algorithm, termed Shrinking LORETA-FOCUSS, which combines and expands upon the central features of two well-known weighted MNLS methods: LORETA and FOCUSS. This recursive algorithm makes iterative adjustments to the solution space as well as the weighting matrix, thereby dramatically reducing the computation load, and increasing local source resolution. Simulations are conducted on a 3-shell spherical head model registered to the Talairach human brain atlas. A comparative study of four different inverse methods, standard Weighted Minimum Norm, L1-norm, LORETA-FOCUSS and Shrinking LORETA-FOCUSS are presented. The results demonstrate that Shrinking LORETA-FOCUSS is able to reconstruct a three-dimensional source distribution with smaller localization and energy errors compared to the other methods.
-
Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans
Tan, Huiling; Pogosyan, Alek; Ashkan, Keyoumars; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Brown, Peter
2016-01-01
The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN) in patients with deep brain stimulation (DBS) electrodes. We found that STN LFP activities in the gamma (55–90 Hz) and beta (13–30m Hz) bands were most informative about gripping force, and that a first order dynamic linear model with these STN LFP features as inputs can be used to decode the temporal profile of gripping force. Our results enhance the understanding of how the basal ganglia control gripping force, and also suggest that deep brain LFPs could potentially be used to decode movement parameters related to force and movement vigour for the development of advanced human-machine interfaces. DOI: http://dx.doi.org/10.7554/eLife.19089.001 PMID:27855780
-
Iofetamine hydrochloride I 123: a new radiopharmaceutical for cerebral perfusion imaging
DOE Office of Scientific and Technical Information (OSTI.GOV)
Druckenbrod, R.W.; Williams, C.C.; Gelfand, M.J.
1989-01-01
Iofetamine hydrochloride I-123 permits cerebral blood perfusion imaging with single photon emission computed tomography (SPECT). SPECT is more widely available than positron emission tomography, and complements anatomic visualization with X-ray computed tomography (CT) or magnetic resonance imaging. Iofetamine is an amphetamine analog that is rapidly taken up by the lungs, then redistributed principally to the liver and brain. The precise mechanism of localization has not been determined, but is believed to result from nonspecific receptor binding. Brain uptake peaks at 30 minutes postinjection and remains relatively constant through 60 minutes. The drug is metabolized and excreted in the urine, withmore » negligible activity remaining at 48 hours. When compared with CT in stroke patients, visualization may be performed sooner after symptom onset and a larger zone of involvement may be evident with iofetamine. Localization of seizure foci and diagnosis of Alzheimer's disease may also be possible. As CT has revolutionized noninvasive imaging of brain anatomy, SPECT with iofetamine permits routine cerebral blood flow imaging. 36 references.« less
-
Role of Monocarboxylate Transporters in Drug Delivery to the Brain
Vijay, Nisha; Morris, Marilyn E.
2014-01-01
Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956
-
Mace, Michael; Pavese, Nicola; Borisyuk, Roman; Bain, Peter
2017-01-01
Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit. PMID:28068428
-
Local entrainment of oscillatory activity induced by direct brain stimulation in humans
Amengual, Julià L.; Vernet, Marine; Adam, Claude; Valero-Cabré, Antoni
2017-01-01
In a quest for direct evidence of oscillation entrainment, we analyzed intracerebral electroencephalographic recordings obtained during intracranial electrical stimulation in a cohort of three medication-resistant epilepsy patients tested pre-surgically. Spectral analyses of non-epileptogenic cerebral sites stimulated directly with high frequency electrical bursts yielded episodic local enhancements of frequency-specific rhythmic activity, phase-locked to each individual pulse. These outcomes reveal an entrainment of physiological oscillatory activity within a frequency band dictated by the rhythm of the stimulation source. Our results support future uses of rhythmic stimulation to elucidate the causal contributions of synchrony to specific aspects of human cognition and to further develop the therapeutic manipulation of dysfunctional rhythmic activity subtending the symptoms of some neuropsychiatric conditions. PMID:28256510
-
Lab Streaming Layer Enabled Myo Data Collection Software User Manual
2017-06-07
time - series data over a local network. LSL handles the networking, time -synchronization, (near-) real- time access as well as, optionally, the... series data collection (e.g., brain activity, heart activity, muscle activity) using the LSL application programming interface (API). Time -synchronized...saved to a single extensible data format (XDF) file. Once the time - series data are collected in a Lab Recorder XDF file, users will be able to query
-
Zhang, Yan; Schuetz, John D; Elmquist, William F; Miller, Donald W
2004-11-01
Several multidrug resistance-associated protein (MRP) homologs are expressed in brain microvessel endothelial cells forming the blood-brain barrier (BBB). The influence of these MRP transporters on BBB permeability will be dependent on their localization within the brain microvessel endothelial cells. Using two different and complementary approaches, the localization of various MPR homologs (MRP1, MRP4, and MRP5) was examined in primary cultured bovine brain microvessel endothelial cells (BBMECs). The first approach involved centrifugal separation of apical and basolateral plasma membranes of cultured BBMECs. The membrane fractions were then subjected to Western blot analysis for MRPs. The second approach used confocal laser scanning microscopy to determine membrane localization of MRPs in BBMECs. Results show a predominantly apical plasma membrane distribution for MRP1 and MRP5, and an almost equal distribution of MRP4 on the apical and basolateral plasma membrane of BBMECs. These studies provide the first demonstration of the localization of MRP1, MRP4, and MRP5 homologs in brain microvessel endothelial cells. The present studies also indicate that the localization of MRPs in the endothelial cells forming the BBB is different from that observed in polarized epithelial cells and thus may contribute to the reduced entry and enhanced elimination of organic anions and nucleotides in the brain.
-
A subharmonic dynamical bifurcation during in vitro epileptiform activity
NASA Astrophysics Data System (ADS)
Perez Velazquez, Jose L.; Khosravani, Houman
2004-06-01
Epileptic seizures are considered to result from a sudden change in the synchronization of firing neurons in brain neural networks. We have used an in vitro model of status epilepticus (SE) to characterize dynamical regimes underlying the observed seizure-like activity. Time intervals between spikes or bursts were used as the variable to construct first-return interpeak or interburst interval plots, for studying neuronal population activity during the transition to seizure, as well as within seizures. Return maps constructed for a brief epoch before seizures were used for approximating the local system dynamics during that time window. Analysis of the first-return maps suggests that intermittency is a dynamical regime underlying the observed epileptic activity. This type of analysis may be useful for understanding the collective dynamics of neuronal populations in the normal and pathological brain.
-
González-Ramírez, Laura R.; Ahmed, Omar J.; Cash, Sydney S.; Wayne, C. Eugene; Kramer, Mark A.
2015-01-01
Epilepsy—the condition of recurrent, unprovoked seizures—manifests in brain voltage activity with characteristic spatiotemporal patterns. These patterns include stereotyped semi-rhythmic activity produced by aggregate neuronal populations, and organized spatiotemporal phenomena, including waves. To assess these spatiotemporal patterns, we develop a mathematical model consistent with the observed neuronal population activity and determine analytically the parameter configurations that support traveling wave solutions. We then utilize high-density local field potential data recorded in vivo from human cortex preceding seizure termination from three patients to constrain the model parameters, and propose basic mechanisms that contribute to the observed traveling waves. We conclude that a relatively simple and abstract mathematical model consisting of localized interactions between excitatory cells with slow adaptation captures the quantitative features of wave propagation observed in the human local field potential preceding seizure termination. PMID:25689136
-
Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals
Koos, Tibor; Buzsáki, György
2012-01-01
Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529
-
Blanco, Igor; Zirak, Peyman; Dragojević, Tanja; Castellvi, Clara; Durduran, Turgut; Justicia, Carles
2017-10-01
Neural activity is an important biomarker for the presence of neurodegenerative diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a surrogate marker for treatment effects. These pathologies may occur and evolve in a long time-period, thus, noninvasive, transcutaneous techniques are necessary to allow a longitudinal follow-up. In the present work, we have customized noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize changes in cerebral blood flow (CBF) induced by neural activity. We were able to detect changes in CBF in the somatosensory cortex by using a model of electrical forepaw stimulation in rats. The suitability of DCS measurements for longitudinal monitoring was demonstrated by performing multiple sessions with the same animals at different ages (from 6 to 18 months). In addition, functional DCS has been cross-validated by comparison with functional magnetic resonance imaging (fMRI) in the same animals in a subset of the time-points. The overall results obtained with transcutaneous DCS demonstrates that it can be utilized in longitudinal studies safely and reproducibly to locate changes in CBF induced by neural activity in the small animal brain.
-
Li, Junyi; Yuan, Yongsheng; Wang, Min; Zhang, Jiejin; Zhang, Li; Jiang, Siming; Ding, Jian; Zhang, Kezhong
2017-10-01
Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.
-
Possible psycho-physiological consequences of human long-term space missions
NASA Astrophysics Data System (ADS)
Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.
Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an
-
Localization and mobility of glucose-coated gold nanoparticles within the brain.
Gromnicova, Radka; Yilmaz, Canan Ugur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather; Williams, Phil; Romero, Ignacio A; Sharrack, Basil; Male, David
2016-03-01
To identify the localization of glucose-coated gold nanoparticles within cells of the brain after intravascular infusion which may point to the mechanism by which they cross the blood-brain barrier. Tissue distribution of the nanoparticles was measured by inductively-coupled-mass spectrometry and localization within the brain by histochemistry and electron microscopy. Nanoparticles were identified within neurons and glial cells more than 10 μm from the nearest microvessel within 10 min of intracarotid infusion. Their distribution indicated movement across the endothelial cytosol, and direct transfer between cells of the brain. The rapid movement of this class of nanoparticle (<5 nm) into the brain demonstrates their potential to carry therapeutic biomolecules or imaging reagents.
-
Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.
Kajikawa, Yoshinao; Smiley, John F; Schroeder, Charles E
2017-10-18
Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. Copyright © 2017 the authors 0270-6474/17/3710139-15$15.00/0.
-
Kim, Daniel H; Schultheiss, Timothy E; Radany, Eric H; Badie, Behnam; Pezner, Richard D
2013-10-01
Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.
-
Osten, Jaime Rendón-von; Soares, Amadeu M V M; Guilhermino, Lucia
2005-02-01
Rice is the main crop in the subbasin of the fluvial lagoon system of Palizada River (FLSPR) in the state of Campeche, Mexico. The pesticides used to control pests of this crop mainly are carbofuran, chlorpyrifos, and glyphosate. Black-bellied whistling duck (Dendrocygna autumnalis) is an ecologically and economically important species in the area. This duck is consumed by local inhabitants throughout the year, despite its potential exposure to pesticides. Due to its feeding habits, abundance, and nutritional value, D. autumnalis is a good indicator of environmental contamination and a potential route of human exposure to organophosphate and carbamate pesticides. In this study, the brain cholinesterase (ChE) in the frontal cerebral cortex of autochthonous ducks was characterized. In addition, the potential of the three locally used pesticides and mixtures to inhibit ChE activity was investigated and the exposure of the wild duck population during intensive pesticide applications in rice fields was evaluated. We found that acetylcholinesterase (AChE) seems to be the predominant ChE form in the biological fraction analyzed. Carbofuran was the most potent ChE inhibitor of D. autumnalis brain ChE activity from the three pesticides analyzed. Cholinesterase inhibition after exposure to pesticide mixtures predominantly was due to carbofuran. A decrease (p < 0.05) in AChE activity (>30%) was apparent in wild ducks compared to reference ducks, with recovery of ChE inhibition in wild ducks occurring months later when no pesticides were applied in the field. Dendrocygna autumnalis brain ChE is a suitable parameter for inclusion in biomonitoring programs for both environmental protection and human safety.
-
Maladaptive Neural Synchrony in Tinnitus: Origin and Restoration
Eggermont, Jos J.; Tass, Peter A.
2015-01-01
Tinnitus is the conscious perception of sound heard in the absence of physical sound sources external or internal to the body, reflected in aberrant neural synchrony of spontaneous or resting-state brain activity. Neural synchrony is generated by the nearly simultaneous firing of individual neurons, of the synchronization of membrane-potential changes in local neural groups as reflected in the local field potentials, resulting in the presence of oscillatory brain waves in the EEG. Noise-induced hearing loss, often resulting in tinnitus, causes a reorganization of the tonotopic map in auditory cortex and increased spontaneous firing rates and neural synchrony. Spontaneous brain rhythms rely on neural synchrony. Abnormal neural synchrony in tinnitus appears to be confined to specific frequency bands of brain rhythms. Increases in delta-band activity are generated by deafferented/deprived neuronal networks resulting from hearing loss. Coordinated reset (CR) stimulation was developed in order to specifically counteract such abnormal neuronal synchrony by desynchronization. The goal of acoustic CR neuromodulation is to desynchronize tinnitus-related abnormal delta-band oscillations. CR neuromodulation does not require permanent stimulus delivery in order to achieve long-lasting desynchronization or even a full-blown anti-kindling but may have cumulative effects, i.e., the effect of different CR epochs separated by pauses may accumulate. Unlike other approaches, acoustic CR neuromodulation does not intend to reduce tinnitus-related neuronal activity by employing lateral inhibition. The potential efficacy of acoustic CR modulation was shown in a clinical proof of concept trial, where effects achieved in 12 weeks of treatment delivered 4–6 h/day persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy, leading to 75% responders. PMID:25741316
-
Chen, Qiu-Feng; Chen, Hua-Jun; Liu, Jun; Sun, Tao; Shen, Qun-Tai
2016-01-01
Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.
-
G5G2.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia.
Murta, Veronica; Schilrreff, Priscila; Rosciszewski, Gerardo; Morilla, Maria Jose; Ramos, Alberto Javier
2018-03-01
Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS, and to specifically target glial cells. In the present work, we explored the use core-shell polyamidoamine tecto-dendrimer (G5G2.5 PAMAM) and studied its ability to target distinct populations of stroke-activated glial cells. We found that G5G2.5 tecto-dendrimer is actively engulfed by primary glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen-glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial G5G2.5 uptake; not being incorporated by neurons or other cell types. We conclude that G5G2.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia. © 2017 International Society for Neurochemistry.
-
Spisák, Tamás; Jakab, András; Kis, Sándor A; Opposits, Gábor; Aranyi, Csaba; Berényi, Ervin; Emri, Miklós
2014-01-01
Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that "resting-state" fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences and preserves real neuronal differences, as demonstrated by the autism-related comparisons.
-
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.
Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel
2015-01-01
Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.
-
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain
Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel
2015-01-01
Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653
-
Decoding the Nature of Emotion in the Brain.
Kragel, Philip A; LaBar, Kevin S
2016-06-01
A central, unresolved problem in affective neuroscience is understanding how emotions are represented in nervous system activity. After prior localization approaches largely failed, researchers began applying multivariate statistical tools to reconceptualize how emotion constructs might be embedded in large-scale brain networks. Findings from pattern analyses of neuroimaging data show that affective dimensions and emotion categories are uniquely represented in the activity of distributed neural systems that span cortical and subcortical regions. Results from multiple-category decoding studies are incompatible with theories postulating that specific emotions emerge from the neural coding of valence and arousal. This 'new look' into emotion representation promises to improve and reformulate neurobiological models of affect. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Decoding the Nature of Emotion in the Brain
Kragel, Philip A.; LaBar, Kevin S.
2016-01-01
A central, unresolved problem in affective neuroscience is understanding how emotions are represented in nervous system activity. After prior localization approaches largely failed, researchers began applying multivariate statistical tools to reconceptualize how emotion constructs might be embedded in large-scale brain networks. Findings from pattern analyses of neuroimaging data show that affective dimensions and emotion categories are uniquely represented in the activity of distributed neural systems that span cortical and subcortical regions. Results from multiple-category decoding studies are incompatible with theories postulating that specific emotions emerge from the neural coding of valence and arousal. This ‘new look’ into emotion representation promises to improve and reformulate neurobiological models of affect. PMID:27133227
-
NASA Astrophysics Data System (ADS)
Capone, Cristiano; Mattia, Maurizio
2017-01-01
Neural field models are powerful tools to investigate the richness of spatiotemporal activity patterns like waves and bumps, emerging from the cerebral cortex. Understanding how spontaneous and evoked activity is related to the structure of underlying networks is of central interest to unfold how information is processed by these systems. Here we focus on the interplay between local properties like input-output gain function and recurrent synaptic self-excitation of cortical modules, and nonlocal intermodular synaptic couplings yielding to define a multiscale neural field. In this framework, we work out analytic expressions for the wave speed and the stochastic diffusion of propagating fronts uncovering the existence of an optimal balance between local and nonlocal connectivity which minimizes the fluctuations of the activation front propagation. Incorporating an activity-dependent adaptation of local excitability further highlights the independent role that local and nonlocal connectivity play in modulating the speed of propagation of the activation and silencing wavefronts, respectively. Inhomogeneities in space of local excitability give raise to a novel hysteresis phenomenon such that the speed of waves traveling in opposite directions display different velocities in the same location. Taken together these results provide insights on the multiscale organization of brain slow-waves measured during deep sleep and anesthesia.
-
Neuropsychology of humor: an introduction. Part II. Humor and the brain.
Derouesné, Christian
2016-09-01
Impairment of the perception or comprehension of humor is observed in patients with focal brain lesions in both hemispheres, but mainly in the right frontal lobe. Studies by functional magnetic resonance imaging in healthy subjects show that humor is associated with activation of two main neural systems in both hemispheres. The detection and resolution of incongruity, cognitive groundings of humor, are associated with activation of the medial prefrontal and temporoparietal cortex, and the humor appreciation with activation of the orbito-frontal and insular cortex, amygdala and the brain reward system. However, activation of these areas is not humor-specific and can be observed in various cognitive or emotional processes. Event-related potential studies confirm the involvement of both hemispheres in humor processing, and suggest that left prefrontal area is associated with joke comprehension and right prefrontal area with the resolution stage. Humor thus appears to be a complex and dynamic functional process involving, on one hand, two specialized but not specific neural systems linked to humor apprehension and appreciation, and, on the other hand, multiple interconnected functional brain networks including neural patterns underlying the moral framework and belief system, acquired by conditioning or imitation during the cognitive development and social interactions of the individual, and more distributed systems associated with the analysis of the current context of humor occurrence. Disturbances of the sense of humor could then result from focal brain alterations localized in one or two of the specialized areas underlying the comprehension or appreciation of humor, or from perturbations of the network interconnectivity in non-focal brain disorders such as Alzheimer's disease or schizophrenia.
-
Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity.
Liu, Huan; Luo, Qi; Du, Wanyi; Li, Xingbao; Zhang, Zhiwei; Yu, Renqiang; Chen, Xiaolu; Meng, Huaqing; Du, Lian
2018-01-03
Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.
-
Zhang, Cong; Bélanger, Samuel; Pouliot, Philippe; Lesage, Frédéric
2015-01-01
In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure.
-
Dendritic protein synthesis in the normal and diseased brain
Swanger, Sharon A.; Bassell, Gary J.
2015-01-01
Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237
-
Su, Wendy; Pasternak, Gavril W.
2013-01-01
The blood brain barrier protects the brain from circulating compounds and drugs. The ATP-binding cassette (ABC) transporter P-glycoprotein (Pgp) is involved with the barrier, both preventing the influx of agent from the blood into the brain and facilitating the efflux of compounds from the brain into the blood, raising the possibility of a similar role for other transporters. Multidrug resistance associated protein (MRP), a 190 kDa protein similar to Pgp is also ABC transport that has been implicated in the blood brain barrier. The current study explores its role in opioid action. Immunohistochemically, it is localized in the choroid plexus in ratsand can be selectively downregulated by antisense treatment at both the level of mRNA, as shown by RT-PCR, and protein, as demonstrated immunohistochemically. Behaviorally, downregulation of MRP significantly enhances the analgesic potency of systemic morphine in MRP knockout mice and in antisense-treated rats by lowering the blood brain barrier. Following intracerebroventricular administration, a number of compounds, including some opioids, are rapidly secreted from the brain into the blood where they contribute to the overall analgesic effects by activating peripheral systems. MRP plays a role in this efflux. Downregulating MRP expression leads to a corresponding decrease in the transport and a diminished analgesic response from opioids administered intracerebroventricularly. Thus, the transporter protein MRP plays a role in maintaining the blood-brain barrier and modulates the activity of opioids. PMID:23508590
-
Developing a system for blind acoustic source localization and separation
NASA Astrophysics Data System (ADS)
Kulkarni, Raghavendra
This dissertation presents innovate methodologies for locating, extracting, and separating multiple incoherent sound sources in three-dimensional (3D) space; and applications of the time reversal (TR) algorithm to pinpoint the hyper active neural activities inside the brain auditory structure that are correlated to the tinnitus pathology. Specifically, an acoustic modeling based method is developed for locating arbitrary and incoherent sound sources in 3D space in real time by using a minimal number of microphones, and the Point Source Separation (PSS) method is developed for extracting target signals from directly measured mixed signals. Combining these two approaches leads to a novel technology known as Blind Sources Localization and Separation (BSLS) that enables one to locate multiple incoherent sound signals in 3D space and separate original individual sources simultaneously, based on the directly measured mixed signals. These technologies have been validated through numerical simulations and experiments conducted in various non-ideal environments where there are non-negligible, unspecified sound reflections and reverberation as well as interferences from random background noise. Another innovation presented in this dissertation is concerned with applications of the TR algorithm to pinpoint the exact locations of hyper-active neurons in the brain auditory structure that are directly correlated to the tinnitus perception. Benchmark tests conducted on normal rats have confirmed the localization results provided by the TR algorithm. Results demonstrate that the spatial resolution of this source localization can be as high as the micrometer level. This high precision localization may lead to a paradigm shift in tinnitus diagnosis, which may in turn produce a more cost-effective treatment for tinnitus than any of the existing ones.
-
Veeraraghavan, Jamunarani; Natarajan, Mohan; Herman, Terence S; Aravindan, Natarajan
2011-01-10
Radiation-induced amplification of reactive oxygen species (ROS) may be a sensing mechanism for activation of signaling cascades that influence cell fate. However, the regulated intrinsic mechanisms and targets of low-dose ionizing radiation (LDIR) are still unclear. Accordingly, we investigated the effects of LDIR on NFκB signal transduction and manganese superoxide dismutase (SOD2) activity in mice brain and gut. LDIR resulted in both dose-dependent and persistent NFκB activation in gut and brain. QPCR displayed a dose- and tissue-dependent differential modulation of 88 signaling molecules. With stringent criteria, a total of 15 (2cGy), 43 (10cGy) and 19 (50cGy) genes were found to be commonly upregulated between brain and gut. SOD2 immunostaining showed a LDIR-dose dependent increase. Consistent with the NFκB results, we observed a persistent increase in SOD2 activity after LDIR. Moreover, muting of LDIR-induced NFκB attenuated SOD2 transactivation and cellular localization. These results imply that exposure of healthy tissues to LDIR results in induced NFκB and SOD2 activity and transcriptional activation of NFκB-signal transduction/target molecules. More importantly, the results suggest that NFκB initiates a feedback response through transcriptional activation of SOD2 that may play a key role in the LDIR-induced oxidative stress response and may control the switch that directs cell fate. 2010 Elsevier B.V. All rights reserved.
-
Hutzler, Michael; Fromherz, Peter
2004-04-01
Probing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field-effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus-response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long-term studies of topographic mapping.
-
Optical Imaging of Targeted β-Galactosidase in Brain Tumors to Detect EGFR Levels
Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James
2015-01-01
A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging. PMID:25775241
-
Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.
Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James
2015-04-15
A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.
-
Rummel, Christoph; Hübschle, Thomas; Gerstberger, Rüdiger; Roth, Joachim
2004-01-01
The purpose of the present study was to investigate a possible lipopolysaccharide (LPS)-induced activation of brain cells that is mediated by the pleiotropic cytokine interleukin-6 (IL-6) and its transcription factor STAT3 during systemic or localized inflammation. In guinea pigs, intra-arterial (i.a., 10 μg kg−1) or intraperitoneal (i.p., 30 μg kg−1) injections of bacterial LPS cause a systemic inflammatory response which is accompanied by a robust fever. A febrile response can also be induced by administration of LPS into artificial subcutaneously implanted Teflon chambers (s.c. 100 or 10 μg kg−1), which reflects an experimental model that mimics local tissue inflammation. Baseline plasma levels of bioactive IL-6 determined 60 min prior to injections of LPS or vehicle amounted to 35–80 international units (i.u.) ml−1. Within 90 min of LPS injection, plasma IL-6 rose about 1000-fold in the groups injected i.a. or i.p., about 50-fold in the group injected s.c. with 100 μg kg−1 LPS, and only 5-fold in guinea pigs injected with the lower dose of LPS (10 μg kg−1). At this time point, a distinct nuclear translocation pattern of the transcription factor STAT3 became evident in several brain structures. Amongst those, the sensory circumventricular organs known to lack a tight blood—brain barrier such as the area postrema, the vascular organ of the lamina terminalis and the subfornical organ, as well as the hypothalamic supraoptic nucleus showed intense nuclear STAT3 signals in the i.a. or i.p. injected groups. In contrast a moderate (s.c. group, 100 μg kg−1), or even no (s.c. group, 10 μg kg−1), nuclear STAT3 translocation occurred in response to s.c. injections of LPS. These results suggest that STAT3-mediated genomic activation of target gene transcription in brain cells occurred only in those cases in which sufficiently high concentrations of circulating IL-6 were formed during systemic (i.a.. and i.p. groups) or localized (s.c. group, 100 μg kg−1) inflammation. PMID:14966301
-
Thul, Alexander; Lechinger, Julia; Donis, Johann; Michitsch, Gabriele; Pichler, Gerald; Kochs, Eberhard F; Jordan, Denis; Ilg, Rüdiger; Schabus, Manuel
2016-02-01
Clinical assessments that rely on behavioral responses to differentiate Disorders of Consciousness are at times inapt because of some patients' motor disabilities. To objectify patients' conditions of reduced consciousness the present study evaluated the use of electroencephalography to measure residual brain activity. We analyzed entropy values of 18 scalp EEG channels of 15 severely brain-damaged patients with clinically diagnosed Minimally-Conscious-State (MCS) or Unresponsive-Wakefulness-Syndrome (UWS) and compared the results to a sample of 24 control subjects. Permutation entropy (PeEn) and symbolic transfer entropy (STEn), reflecting information processes in the EEG, were calculated for all subjects. Participants were tested on a modified active own-name paradigm to identify correlates of active instruction following. PeEn showed reduced local information content in the EEG in patients, that was most pronounced in UWS. STEn analysis revealed altered directed information flow in the EEG of patients, indicating impaired feed-backward connectivity. Responses to auditory stimulation yielded differences in entropy measures, indicating reduced information processing in MCS and UWS. Local EEG information content and information flow are affected in Disorders of Consciousness. This suggests local cortical information capacity and feedback information transfer as neural correlates of consciousness. The utilized EEG entropy analyses were able to relate to patient groups with different Disorders of Consciousness. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
-
Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism.
Soares, Ana Francisca; Gruetter, Rolf; Lei, Hongxia
2017-07-15
In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy ( 13 C-MRS) in vivo. With this approach, glycogen synthesis and degradation may be followed in real time, thereby providing valuable insights into brain glycogen dynamics. However, compared to the liver and muscle, where glycogen is abundant, the sensitivity for detection of brain glycogen by 13 C-MRS is inherently low. In this review we focus on strategies used to optimize the sensitivity for 13 C-MRS detection of glycogen. Namely, we explore several technical perspectives, such as magnetic field strength, field homogeneity, coil design, decoupling, and localization methods. Furthermore, we also address basic principles underlying the use of 13 C-labeled precursors to enhance the detectable glycogen signal, emphasizing specific experimental aspects relevant for obtaining kinetic information on brain glycogen. Copyright © 2016 Elsevier Inc. All rights reserved.
-
Jeong, Eun-Kee; Sung, Young-Hoon; Kim, Seong-Eun; Zuo, Chun; Shi, Xianfeng; Mellon, Eric A; Renshaw, Perry F
2011-08-01
High-energy phosphate metabolism, which allows the synthesis and regeneration of adenosine triphosphate (ATP), is a vital process for neuronal survival and activity. In particular, creatine kinase (CK) serves as an energy reservoir for the rapid buffering of ATP levels. Altered CK enzyme activity, reflecting compromised high-energy phosphate metabolism or mitochondrial dysfunction in the brain, can be assessed using magnetization transfer (MT) MRS. MT (31)P MRS has been used to measure the forward CK reaction rate in animal and human brain, employing a surface radiofrequency coil. However, long acquisition times and excessive radiofrequency irradiation prevent these methods from being used routinely for clinical evaluations. In this article, a new MT (31)P MRS method is presented, which can be practically used to measure the CK forward reaction rate constant in a clinical MRI system employing a volume head (31)P coil for spatial localization, without contamination from the scalp muscle, and an acquisition time of 30 min. Other advantages associated with the method include radiofrequency homogeneity within the regions of interest of the brain using a volume coil with image-selected in vivo spectroscopy localization, and reduction of the specific absorption rate using nonadiabatic radiofrequency pulses for MT saturation. The mean value of k(f) was measured as 0.320 ± 0.075 s(-1) from 10 healthy volunteers with an age range of 18-40 years. These values are consistent with those obtained using earlier methods, and the technique may be used routinely to evaluate energetic processes in the brain on a clinical MRI system. Copyright © 2010 John Wiley & Sons, Ltd.
-
Tamura, Yukie; Ogawa, Hiroshi; Kapeller, Christoph; Prueckl, Robert; Takeuchi, Fumiya; Anei, Ryogo; Ritaccio, Anthony; Guger, Christoph; Kamada, Kyousuke
2016-12-01
OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.
-
Vidal, Juan R.; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe
2015-01-01
If conscious perception requires global information integration across active distant brain networks, how does the loss of conscious perception affect neural processing in these distant networks? Pioneering studies on perceptual suppression (PS) described specific local neural network responses in primary visual cortex, thalamus and lateral prefrontal cortex of the macaque brain. Yet the neural effects of PS have rarely been studied with intracerebral recordings outside these cortices and simultaneously across distant brain areas. Here, we combined (1) a novel experimental paradigm in which we produced a similar perceptual disappearance and also re-appearance by using visual adaptation with transient contrast changes, with (2) electrophysiological observations from human intracranial electrodes sampling wide brain areas. We focused on broadband high-frequency (50–150 Hz, i.e., gamma) and low-frequency (8–24 Hz) neural activity amplitude modulations related to target visibility and invisibility. We report that low-frequency amplitude modulations reflected stimulus visibility in a larger ensemble of recording sites as compared to broadband gamma responses, across distinct brain regions including occipital, temporal and frontal cortices. Moreover, the dynamics of the broadband gamma response distinguished stimulus visibility from stimulus invisibility earlier in anterior insula and inferior frontal gyrus than in temporal regions, suggesting a possible role of fronto-insular cortices in top–down processing for conscious perception. Finally, we report that in primary visual cortex only low-frequency amplitude modulations correlated directly with perceptual status. Interestingly, in this sensory area broadband gamma was not modulated during PS but became positively modulated after 300 ms when stimuli were rendered visible again, suggesting that local networks could be ignited by top–down influences during conscious perception. PMID:25642199
-
Brain processing of meter and rhythm in music. Electrophysiological evidence of a common network.
Kuck, Heleln; Grossbach, Michael; Bangert, Marc; Altenmüller, Eckart
2003-11-01
To determine cortical structures involved in "global" meter and "local" rhythm processing, slow brain potentials (DC potentials) were recorded from the scalp of 18 musically trained subjects while listening to pairs of monophonic sequences with both metric structure and rhythmic variations. The second sequence could be either identical to or different from the first one. Differences were either of a metric or a rhythmic nature. The subjects' task was to judge whether the sequences were identical or not. During processing of the auditory tasks, brain activation patterns along with the subjects' performance were assessed using 32-channel DC electroencephalography. Data were statistically analyzed using MANOVA. Processing of both meter and rhythm produced sustained cortical activation over bilateral frontal and temporal brain regions. A shift towards right hemispheric activation was pronounced during presentation of the second stimulus. Processing of rhythmic differences yielded a more centroparietal activation compared to metric processing. These results do not support Lerdhal and Jackendoff's two-component model, predicting a dissociation of left hemispheric rhythm and right hemispheric meter processing. We suggest that the uniform right temporofrontal predominance reflects auditory working memory and a pattern recognition module, which participates in both rhythm and meter processing. More pronounced parietal activation during rhythm processing may be related to switching of task-solving strategies towards mental imagination of the score.
-
Kinreich, Sivan; Intrator, Nathan; Hendler, Talma
2011-01-01
One of the greatest challenges involved in studying the brain mechanisms of fear is capturing the individual's unique instantaneous experience. Brain imaging studies to date commonly sacrifice valuable information regarding the individual real-time conscious experience, especially when focusing on elucidating the amygdala's activity. Here, we assumed that by using a minimally intrusive cue along with applying a robust clustering approach to probe the amygdala, it would be possible to rate fear in real time and to derive the related network of activation. During functional magnetic resonance imaging scanning, healthy volunteers viewed two excerpts from horror movies and were periodically auditory cued to rate their instantaneous experience of "I'm scared." Using graph theory and community mathematical concepts, data-driven clustering of the fear-related functional cliques in the amygdala was performed guided by the individually marked periods of heightened fear. Individually tailored functions derived from these amygdala activation cliques were subsequently applied as general linear model predictors to a whole-brain analysis to reveal the correlated networks. Our results suggest that by using a localized robust clustering approach, it is possible to probe activation in the right dorsal amygdala that is directly related to individual real-time emotional experience. Moreover, this fear-evoked amygdala revealed two opposing networks of co-activation and co-deactivation, which correspond to vigilance and rest-related circuits, respectively.
-
The direct relationship between inhibitory currents and local field potentials.
Trevelyan, Andrew J
2009-12-02
The frequency profiles of various extracellular field oscillations are known to reflect functional brain states, yet we lack detailed explanations of how these brain oscillations arise. Of particular clinical relevance are the high-frequency oscillations (HFOs) associated with interictal events and the onset of seizures. These time periods are also when pyramidal firing appears to be vetoed by high-frequency volleys of inhibitory synaptic currents, thereby providing an inhibitory restraint that opposes epileptiform spread (Trevelyan et al., 2006, 2007). The pattern and timing of this inhibitory volley is suggestive of a causal relationship between the restraint and HFOs. I show that at these times, isolated inhibitory currents from single pyramidal cells have a similarity to the extracellular signal that significantly exceeds chance. The ability to extrapolate from discrete currents in single cells to the extracellular signal arises because these inhibitory currents are synchronized in local populations of pyramidal cells. The visibility of these inhibitory currents in the field recordings is greatest when local pyramidal activity is suppressed: the correlation between the inhibitory currents and the field signal becomes worse when local activity increases, suggestive of a switch from one source of HFO to another as the restraint starts to fail. This association suggests that a significant component of HFOs reflects the last act of defiance in the face of an advancing ictal event.
-
Mathewson, Kyle E.; Beck, Diane M.; Ro, Tony; Maclin, Edward L.; Low, Kathy A.; Fabiani, Monica; Gratton, Gabriele
2015-01-01
We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously we proposed that alpha (8-12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top-down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently-recorded electroencephalogram (EEG), while subjects performed a visual target-detection task. The pre-target alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha's inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across subjects. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network, and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks prior to posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top-down control from attention networks modulates both posterior alpha and awareness of visual stimuli. PMID:24702458
-
Regions of mid-level human visual cortex sensitive to the global coherence of local image patches.
Mannion, Damien J; Kersten, Daniel J; Olman, Cheryl A
2014-08-01
The global structural arrangement and spatial layout of the visual environment must be derived from the integration of local signals represented in the lower tiers of the visual system. This interaction between the spatially local and global properties of visual stimulation underlies many of our visual capacities, and how this is achieved in the brain is a central question for visual and cognitive neuroscience. Here, we examine the sensitivity of regions of the posterior human brain to the global coordination of spatially displaced naturalistic image patches. We presented observers with image patches in two circular apertures to the left and right of central fixation, with the patches drawn from either the same (coherent condition) or different (noncoherent condition) extended image. Using fMRI at 7T (n = 5), we find that global coherence affected signal amplitude in regions of dorsal mid-level cortex. Furthermore, we find that extensive regions of mid-level visual cortex contained information in their local activity pattern that could discriminate coherent and noncoherent stimuli. These findings indicate that the global coordination of local naturalistic image information has important consequences for the processing in human mid-level visual cortex.
-
Gratton, Gabriele
2018-03-01
Here, I propose a view of the architecture of the human information processing system, and of how it can be adapted to changing task demands (which is the hallmark of cognitive control). This view is informed by an interpretation of brain activity as reflecting the excitability level of neural representations, encoding not only stimuli and temporal contexts, but also action plans and task goals. The proposed cognitive architecture includes three types of circuits: open circuits, involved in feed-forward processing such as that connecting stimuli with responses and characterized by brief, transient brain activity; and two types of closed circuits, positive feedback circuits (characterized by sustained, high-frequency oscillatory activity), which help select and maintain representations, and negative feedback circuits (characterized by brief, low-frequency oscillatory bursts), which are instead associated with changes in representations. Feed-forward activity is primarily responsible for the spread of activation along the information processing system. Oscillatory activity, instead, controls this spread. Sustained oscillatory activity due to both local cortical circuits (gamma) and longer corticothalamic circuits (alpha and beta) allows for the selection of individuated representations. Through the interaction of these circuits, it also allows for the preservation of representations across different temporal spans (sensory and working memory) and their spread across the brain. In contrast, brief bursts of oscillatory activity, generated by novel and/or conflicting information, lead to the interruption of sustained oscillatory activity and promote the generation of new representations. I discuss how this framework can account for a number of psychological and behavioral phenomena. © 2017 Society for Psychophysiological Research.
-
Nair, Arun T; Ramachandran, Vadivelan; Joghee, Nanjan M; Antony, Shanish; Ramalingam, Gopalakrishnan
2018-01-01
Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients. PMID:29291606
-
Wei, Ling; Li, Yingjie; Yang, Xiaoli; Xue, Qing; Wang, Yuping
2015-10-01
The present study evaluated the topological properties of whole brain networks using graph theoretical concepts and investigated the time-evolution characteristic of brain network in mild cognitive impairment patients during a selective attention task. Electroencephalography (EEG) activities were recorded in 10 MCI patients and 17 healthy subjects when they performed a color match task. We calculated the phase synchrony index between each possible pairs of EEG channels in alpha and beta frequency bands and analyzed the local interconnectedness, overall connectedness and small-world characteristic of brain network in different degree for two groups. Relative to healthy normal controls, the properties of cortical networks in MCI patients tend to be a shift of randomization. Lower σ of MCI had suggested that patients had a further loss of small-world attribute both during active and resting states. Our results provide evidence for the functional disconnection of brain regions in MCI. Furthermore, we found the properties of cortical networks could reflect the processing of conflict information in the selective attention task. The human brain tends to be a more regular and efficient neural architecture in the late stage of information processing. In addition, the processing of conflict information needs stronger information integration and transfer between cortical areas. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Black, Paul J.; Page, Brandi R.; Lucas, John T.; Qasem, Shadi A.; Watabe, Kounosuke; Ruiz, Jimmy; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar; Chan, Michael D.
2016-01-01
Purpose We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). Methods and materials Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. Results Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). Conclusions WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS. PMID:29296433
-
The role of the immune system in central nervous system plasticity after acute injury.
Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano
2014-12-26
Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
-
CEREBRA: a 3-D visualization tool for brain network extracted from fMRI data.
Nasir, Baris; Yarman Vural, Fatos T
2016-08-01
In this paper, we introduce a new tool, CEREBRA, to visualize the 3D network of human brain, extracted from the fMRI data. The tool aims to analyze the brain connectivity by representing the selected voxels as the nodes of the network. The edge weights among the voxels are estimated by considering the relationships among the voxel time series. The tool enables the researchers to observe the active brain regions and the interactions among them by using graph theoretic measures, such as, the edge weight and node degree distributions. CEREBRA provides an interactive interface with basic display and editing options for the researchers to study their hypotheses about the connectivity of the brain network. CEREBRA interactively simplifies the network by selecting the active voxels and the most correlated edge weights. The researchers may remove the voxels and edges by using local and global thresholds selected on the window. The built-in graph reduction algorithms are then eliminate the irrelevant regions, voxels and edges and display various properties of the network. The toolbox is capable of space-time representation of the voxel time series and estimated arc weights by using the animated heat maps.
-
Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano
2014-01-01
Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.
-
Reduced local field potential power in the medial prefrontal cortex by noxious stimuli.
Li, Ai-Ling; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo
2016-10-01
Nociceptive signals produced by noxious stimuli at the periphery reach the brain through ascending pathways. These signals are processed by various brain areas and lead to activity changes in those areas. The medial prefrontal cortex (mPFC) is involved in higher cognitive functions and emotional processing. It receives projections from brain areas involved in nociception. In this study, we investigated how nociceptive input from the periphery changes the local field potential (LFP) activity in the mPFC. Three different types of noxious stimuli were applied to the hind paw contralateral to the LFP recording site. They were transcutaneous electrical stimulations, mechanical stimuli and a chemical stimulus (formalin injection). High intensity transcutaneous stimulations (10V to 50V) and noxious mechanical stimulus (pinch) significantly reduced the LFP power during the stimulating period (p<0.05), but not the low intensity subcutaneous stimulations (0.1V to 5V) and other innocuous mechanical stimuli (brush and pressure). More frequency bands were inhibited with increased intensity of transcutaneous electrical stimulation, and almost all frequency bands were inhibited by stimulations at or higher than 30v. Pinch significantly reduced the power for beta band and formalin injection significantly reduced the power of alpha and beta band. Our data demonstrated the noxious stimuli-induced reduction of LFP power in the mPFC, which indicates the active processing of nociceptive information by the mPFC. Copyright © 2016 Elsevier Inc. All rights reserved.
-
Rossion, Bruno; Dricot, Laurence; Goebel, Rainer; Busigny, Thomas
2011-01-01
How a visual stimulus is initially categorized as a face in a network of human brain areas remains largely unclear. Hierarchical neuro-computational models of face perception assume that the visual stimulus is first decomposed in local parts in lower order visual areas. These parts would then be combined into a global representation in higher order face-sensitive areas of the occipito-temporal cortex. Here we tested this view in fMRI with visual stimuli that are categorized as faces based on their global configuration rather than their local parts (two-tones Mooney figures and Arcimboldo's facelike paintings). Compared to the same inverted visual stimuli that are not categorized as faces, these stimuli activated the right middle fusiform gyrus (“Fusiform face area”) and superior temporal sulcus (pSTS), with no significant activation in the posteriorly located inferior occipital gyrus (i.e., no “occipital face area”). This observation is strengthened by behavioral and neural evidence for normal face categorization of these stimuli in a brain-damaged prosopagnosic patient whose intact right middle fusiform gyrus and superior temporal sulcus are devoid of any potential face-sensitive inputs from the lesioned right inferior occipital cortex. Together, these observations indicate that face-preferential activation may emerge in higher order visual areas of the right hemisphere without any face-preferential inputs from lower order visual areas, supporting a non-hierarchical view of face perception in the visual cortex. PMID:21267432
-
Epilepsy, regulation of brain energy metabolism and neurotransmission.
Cloix, Jean-François; Hévor, Tobias
2009-01-01
Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.
-
Weisz, Nathan; Obleser, Jonas
2014-01-01
Human magneto- and electroencephalography (M/EEG) are capable of tracking brain activity at millisecond temporal resolution in an entirely non-invasive manner, a feature that offers unique opportunities to uncover the spatiotemporal dynamics of the hearing brain. In general, precise synchronisation of neural activity within as well as across distributed regions is likely to subserve any cognitive process, with auditory cognition being no exception. Brain oscillations, in a range of frequencies, are a putative hallmark of this synchronisation process. Embedded in a larger effort to relate human cognition to brain oscillations, a field of research is emerging on how synchronisation within, as well as between, brain regions may shape auditory cognition. Combined with much improved source localisation and connectivity techniques, it has become possible to study directly the neural activity of auditory cortex with unprecedented spatio-temporal fidelity and to uncover frequency-specific long-range connectivities across the human cerebral cortex. In the present review, we will summarise recent contributions mainly of our laboratories to this emerging domain. We present (1) a more general introduction on how to study local as well as interareal synchronisation in human M/EEG; (2) how these networks may subserve and influence illusory auditory perception (clinical and non-clinical) and (3) auditory selective attention; and (4) how oscillatory networks further reflect and impact on speech comprehension. This article is part of a Special Issue entitled Human Auditory Neuroimaging. Copyright © 2013 Elsevier B.V. All rights reserved.
-
Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells
ERIC Educational Resources Information Center
Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.
2013-01-01
In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…
-
Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance
ERIC Educational Resources Information Center
Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.
2010-01-01
Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…
-
Cameron-Burr, Keaton T.; Shaham, Yavin
2017-01-01
Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100–200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity. PMID:28593192
-
Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto
2013-01-01
Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes. PMID:24478697
-
Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto
2014-01-01
Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.
-
Allegra, Mario; Carletti, Fabio; Gambino, Giuditta; Tutone, Marco; Attanzio, Alessandro; Tesoriere, Luisa; Ferraro, Giuseppe; Sardo, Pierangelo; Almerico, Anna Maria; Livrea, Maria Antonia
2015-08-26
Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependently modulated the rate of discharge of spontaneously active neurons of the hippocampus, with reduction of the discharge and related changes of latency and duration of the effect. Indicaxanthin (0.34 ng/neuron) showed inhibitory effects on glutamate-induced excitation, indicating activity at the level of glutamatergic synapses. A molecular target of indicaxanthin is suggested by in silico molecular modeling of indicaxanthin with N-methyl-D-aspartate receptor (NMDAR), the most represented of the glutamate receptor family in hippocampus. Therefore, at nutritionally compatible amounts indicaxanthin (i) crosses the rat BBB and accumulates in brain; (ii) can affect the bioelectric activity of hippocampal neurons locally treated with amounts comparable with those measured in the brain; and (iii) modulates glutamate-induced neuronal excitation. The potential of dietary indicaxanthin as a natural neuromodulatory agent deserves further mechanistic and neurophysiologic investigation.
-
Huang, Ying; Matysiak, Artur; Heil, Peter; König, Reinhard; Brosch, Michael
2016-01-01
Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys. DOI: http://dx.doi.org/10.7554/eLife.15441.001 PMID:27438411
-
Dienel, Gerald A; Cruz, Nancy F
2016-07-01
Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain activation. Aerobic glycolysis, the preferential up-regulation of glucose utilization (CMRglc ) compared with oxygen consumption (CMRO2 ) during brain activation, is blocked by propranolol. Epinephrine release from the adrenal gland stimulates vagus nerve signaling to the locus coeruleus, enhancing norepinephrine release in the brain, and regulation of astrocytic and neuronal metabolism to stimulate CMRglc more than CMRO2 . Propranolol suppresses CMRglc more than CMRO2 . © 2016 International Society for Neurochemistry.
-
Coughlin, Jennifer M; Wang, Yuchuan; Minn, Il; Bienko, Nicholas; Ambinder, Emily B; Xu, Xin; Peters, Matthew E; Dougherty, John W; Vranesic, Melin; Koo, Soo Min; Ahn, Hye-Hyun; Lee, Merton; Cottrell, Chris; Sair, Haris I; Sawa, Akira; Munro, Cynthia A; Nowinski, Christopher J; Dannals, Robert F; Lyketsos, Constantine G; Kassiou, Michael; Smith, Gwenn; Caffo, Brian; Mori, Susumu; Guilarte, Tomas R; Pomper, Martin G
2017-01-01
Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.
-
Aberrant patterns of local and long-range functional connectivity densities in schizophrenia
Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun
2017-01-01
Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions. PMID:28654893
-
Aberrant patterns of local and long-range functional connectivity densities in schizophrenia.
Liu, Chuanxin; Zhang, Wei; Chen, Guangdong; Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun
2017-07-18
Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.
-
Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah
2014-11-01
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
-
Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah
2014-01-01
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826
-
Nuclear localization of Klotho in brain: an anti-aging protein
German, Dwight C.; Khobahy, Ida; Pastor, Johanne; Kuro-o, Makoto; Liu, Xinran
2011-01-01
Klotho is a putative age-suppressing gene whose over-expression in mice results in extension of life span. The klotho gene encodes a single-pass transmembrane protein whose extracellular domain is shed and released into blood, urine, and cerebrospinal fluid, potentially functioning as a humoral factor. The extracellular domain of Klotho has an activity that increases the expression of anti-oxidant enzymes and confers resistance to oxidative stress in cultured cells and in whole animals. The transmembrane form of the Klotho protein directly binds to multiple fibroblast growth factor receptors and modifies their ligand affinity and specificity. The purpose of the present study was to determine the precise cellular localization of Klotho in the mouse brain. Using light microscopic immunohistochemical methods, we found the highest levels of Klotho immunoreactivity in two brain regions: the choroid plexus, and cerebellar Purkinje cells. In the choroid plexus cells, Klotho was found not only on the plasma membrane but also in large amounts near the nuclear membrane. Likewise, in the Purkinje cell Klotho was found throughout the cell including dendrites, axon and soma with large amounts near the nuclear membrane. Using immunoelectron microscopy, we found Klotho in the cell membrane, but the highest concentration was localized in the peripheral portion of the nucleus and the nucleolus in both cell types. This new finding suggests that in addition to Klotho being secreted from cells in brain, it also has a nuclear function. PMID:22245317
-
... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury Going Local to Find Help Past Issues / Fall ... all the time. From the MedlinePlus page on Traumatic Brain Injury, you can use Go Local to find specific ...
-
Matsuda, Junko; Vanier, Marie T.; Popa, Iuliana; Portoukalian, Jacques; Suzuki, Kunihiko
2006-01-01
Gangliosides in the brain of the knockout mouse deficient in the activity of β1,4 N-acetylgalactosaminyl transferase (β1,4 GalNAc-T)(GM2 synthase) consisted of nearly exclusively of GM3- and GD3-gangliosides as expected from the known substrate specificity of the enzyme and in confirmation of the initial reports from two laboratories that generated the mutant mouse experimentally. The total molar amount of gangliosides was approximately 30% higher in the mutant mouse brain than that in the wild-type brain. However, contrary to the initial reports, one-fourth of total GD3-ganglioside was O-acetylated. It reacted positively with an anti-O-acetylated GD3 monoclonal antibody and disappeared with a corresponding increase in GD3-ganglioside after mild alkaline treatment. The absence of O-acetylated GD3 in the initial reports can be explained by the saponification step included in their analytical procedures. Although quantitatively much less and identification tentative, we also detected GT3 and O-acetylated GT3. Anti-GD3 and anti-O-acetylated GD3 monoclonal antibodies gave positive reactions in the brain of mutant mouse as expected from the analytical results. Either antibody barely stained wild-type brain except for immunoreactivity of GD3 in the cerebellar Purkinje cells. The distributions of GD3 and O-acetylated GD3 in the brain of mutant mouse were similar but differential localization was noted in the cerebellar Purkinje cells and cerebral cortex. PMID:25792782
-
NASA Astrophysics Data System (ADS)
Zhang, Zhongxing; Khatami, Ramin
2013-03-01
The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, p<0.05) during SWS compared to light sleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.
-
Stratoulias, Vassilis; Heino, Tapio I
2015-05-01
Glia are abundant cells in the brain of animals ranging from flies to humans. They perform conserved functions not only in neural development and wiring, but also in brain homeostasis. Here we show that by manipulating gene expression in glia, a previously unidentified cell type appears in the Drosophila brain during metamorphosis. More specifically, this cell type appears in three contexts: (1) after the induction of either immunity, or (2) autophagy, or (3) by silencing of neurotrophic factor DmMANF in glial cells. We call these cells MANF immunoreactive Cells (MiCs). MiCs are migratory based on their shape, appearance in brain areas where no cell bodies exist and the nuclear localization of dSTAT. They are labeled with a unique set of molecular markers including the conserved neurotrophic factor DmMANF and the transcription factor Zfh1. They possess the nuclearly localized protein Relish, which is the hallmark of immune response activation. They also express the conserved engulfment receptor Draper, therefore indicating that they are potentially phagocytic. Surprisingly, they do not express any of the common glial and neuronal markers. In addition, ultrastructural studies show that MiCs are extremely rich in lysosomes. Our findings reveal critical molecular and functional components of an unusual cell type in the Drosophila brain. We suggest that MiCs resemble macrophages/hemocytes and vertebrate microglia based on their appearance in the brain upon genetically challenged conditions and the expression of molecular markers. Interestingly, macrophages/hemocytes or microglia-like cells have not been reported in the fly nervous system before.
-
Changes in the organ procurement system in South Korea: effects on brain-dead donor numbers.
Lee, S D; Kim, J H
2009-11-01
In Korea, the Organ Transplantation Act came into effect in 2000, establishing the Korean Network for Organ Sharing (KONOS) with centralized authority for organ procurement as well as for approval of donors and recipients to ensure fair organ allocation. However, the number of brain-dead donors decreased sharply, and the organ allocation system proved inefficient. The government revised the Organ Transplantation Act in August 2002, introducing an incentive system. If a transplantation hospital formed a Committee for Brain Death Evaluation and a Hospital Organ Procurement Organization, it could receive a kidney from a brain dead-donor as an incentive to foster organ procurement regardless of the KONOS wait list. The government also launched a pilot brain-dead donor registry program to strengthen Hospital Organ Procurement Organization activity. If local hospitals collaborated with specialized hospitals in organ procurement, local hospitals obtained financial incentives. But because the organ shortage problem has not been resolved, the government has proposed four initiatives: first, broadening the incentive system, which makes it possible to give each specialized hospital a choice of one of eight organs from each donor as an incentive; second, development of an Independent Organ Procurement Organization; third introduction of an opt-out system; and last, improvement of the Committee for Brain Death Evaluation system. It is uncertain which initiatives will be adopted, but changes in organ procurement systems are nonetheless considered a key to solve the organ shortage problem in Korea.
-
NASA Astrophysics Data System (ADS)
Molteni, Erika; Contini, Davide; Caffini, Matteo; Baselli, Giuseppe; Spinelli, Lorenzo; Cubeddu, Rinaldo; Cerutti, Sergio; Bianchi, Anna Maria; Torricelli, Alessandro
2012-05-01
We evaluated frontal brain activation during a mixed attentional/working memory task with graded levels of difficulty in a group of 19 healthy subjects, by means of time-domain functional near-infrared spectroscopy (fNIRS). Brain activation was assessed, and load-related oxy- and deoxy-hemoglobin changes were studied. Generalized linear model (GLM) was applied to the data to explore the metabolic processes occurring during the mental effort and, possibly, their involvement in short-term memorization. GLM was applied to the data twice: for modeling the task as a whole and for specifically investigating brain activation at each cognitive load. This twofold employment of GLM allowed (1) the extraction and isolation of different information from the same signals, obtained through the modeling of different cognitive categories (sustained attention and working memory), and (2) the evaluation of model fitness, by inspection and comparison of residuals (i.e., unmodeled part of the signal) obtained in the two different cases. Results attest to the presence of a persistent attentional-related metabolic activity, superimposed to a task-related mnemonic contribution. Some hemispherical differences have also been highlighted frontally: deoxy-hemoglobin changes manifested a strong right lateralization, whereas modifications in oxy- and total hemoglobin showed a medial localization. The present work successfully explored the capability of fNIRS to detect the two neurophysiological categories under investigation and distinguish their activation patterns.
-
Estrogen-2-hydroxylase in the brain of the male African catfish, Clarias gariepinus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Timmers, R.J.; Granneman, J.C.; Lambert, J.G.
1988-11-01
Estrogen-2-hydroxylase activity, involved in the biosynthesis of catecholestrogens, was localized in the brain of the male African catfish, Clarias gariepinus, by means of a radiometric assay using (2-TH)estradiol as substrate. Fore- and midbrain were divided in 18, 500-microns thick, transverse sections from which small defined areas were punched out and assayed. The estrogen-2-hydroxylase activity was calculated from the release of tritium during hydroxylation, and expressed in femtomole catecholestradiol.milligram-1 tissue.hour-1. The enzyme could be demonstrated throughout the brain. A high activity (greater than 350 fmol) was observed in the telencephalon, in particularly the rostral part and the area ventralis pars dorsalis;more » in the diencephalon in the preoptic region, including the magnocellular part of the preoptic nucleus and the rostral part of the anterior periventricular nucleus; and in the area tuberalis, including the nucleus lateralis tuberis, the rostral part of the nucleus anterior tuberis, the caudal part of the nucleus posterior periventricularis, and in the nucleus recessus posterioris. Also a high activity was detected in the mesencephalic tectum opticum and the dorsolateral part of the torus semicircularis. The ventral mesencephalon showed a moderate (200-350 fmol) to low (less than 200 fmol) activity, whereas the lowest activity was found in the hindbrain (118 fmol). The significance of the biosynthesis of catecholestrogens in the brain is discussed in light of the negative feedback mechanism of gonadal steroids on gonadotropin release.« less
-
The neuropathology of morality: Germany 1930-1960.
Schirmann, Felix
2014-01-01
This article analyzes brain scientists' attempts to trace morality in the brain in Germany from 1930 to 1960. The debate around Karl Kleist's localization of the Gemeinschafts-Ich [community-I] in the 1930s is depicted in order to illustrate the central arguments for and against localizations of morality. The focus of this article is on the period 1936-1960 in which experts put forth specific ideas on morality's cerebral underpinnings that mirror the larger theoretical shift from strict localization doctrine to a more holistic understanding of the brain. As a result of this shift, experts avoided exact localizations of morality. Instead, they posited correlations between brain areas and morality. The analysis illustrates the dependence of neuropathological research on morality on general theories of brain functioning and marks a first contribution to the history of the neuroscience of morality for the time after 1930.
-
Spatio-Temporal Information Analysis of Event-Related BOLD Responses
Alpert, Galit Fuhrmann; Handwerker, Dan; Sun, Felice T.; D’Esposito, Mark; Knight, Robert T.
2009-01-01
A new approach for analysis of event related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task related activity, as well as for extracting temporal information regarding the task dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF), nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times. PMID:17188515
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; IRCCS Neuromed, Pozzilli; Scaringi, Claudia
Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, amore » propensity score analysis was used. Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.« less
-
Different forms of effective connectivity in primate frontotemporal pathways.
Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K
2015-01-23
It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.
-
Different forms of effective connectivity in primate frontotemporal pathways
Petkov, Christopher I.; Kikuchi, Yukiko; Milne, Alice E.; Mishkin, Mortimer; Rauschecker, Josef P.; Logothetis, Nikos K.
2015-01-01
It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex. PMID:25613079
-
Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark
2015-01-01
Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231
-
Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT).
Åslund, Andreas K O; Snipstad, Sofie; Healey, Andrew; Kvåle, Svein; Torp, Sverre H; Sontum, Per C; Davies, Catharina de Lange; van Wamel, Annemieke
2017-01-01
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.
-
Serletis, Demitre; Bardakjian, Berj L; Valiante, Taufik A; Carlen, Peter L
2012-10-01
Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/f(γ) noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders.
-
Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands.
Deligianni, Fani; Centeno, Maria; Carmichael, David W; Clayden, Jonathan D
2014-01-01
Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity.
-
Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands
Deligianni, Fani; Centeno, Maria; Carmichael, David W.; Clayden, Jonathan D.
2014-01-01
Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity. PMID:25221467
-
Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S
Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.
-
The two-pore domain K+ channel TASK-1 is closely associated with brain barriers and meninges.
Kanjhan, Refik; Pow, David V; Noakes, Peter G; Bellingham, Mark C
2010-12-01
Impairment of the blood-brain barrier (BBB), the blood-cerebrospinal fluid (CSF) barrier and brain-CSF barrier has been implicated in neuropathology of several brain disorders, such as amyotrophic lateral sclerosis, cerebral edema, multiple sclerosis, neural inflammation, ischemia and stroke. Two-pore domain weakly inward rectifying K+ channel (TWIK)-related acid-sensitive potassium (TASK)-1 channels (K2p3.1; KCNK3) are among the targets that contribute to the development of these pathologies. For example TASK-1 activity is inhibited by acidification, ischemia, hypoxia and several signaling molecules released under pathologic conditions. We have used immuno-histochemistry to examine the distribution of the TASK-1 protein in structures associated with the BBB, blood-CSF barrier, brain-CSF barrier, and in the meninges of adult rat. Dense TASK-1 immuno-reactivity (TASK-1-IR) was observed in ependymal cells lining the fourth ventricle at the brain-CSF interface, in glial cells that ensheath the walls of blood vessels at the glio-vascular interface, and in the meninges. In these structures, TASK-1-IR often co-localized with glial fibrillary associated protein (GFAP) or vimentin. This study provides anatomical evidence for localization of TASK-1 K+ channels in cells that segregate distinct fluid compartments within and surrounding the brain. We suggest that TASK-1 channels, in coordination with other ion channels (e.g., aquaporins and chloride channels) and transporters (e.g., Na+-K+-ATPase and Na+-K+-2Cl⁻ and by virtue of its heterogeneous distribution, may differentially contribute to the varying levels of K+ vital for cellular function in these compartments. Our findings are likely to be relevant to recently reported roles of TASK-1 in cerebral ischemia, stroke and inflammatory brain disorders.
-
Hemispheric asymmetry of electroencephalography-based functional brain networks.
Jalili, Mahdi
2014-11-12
Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.
-
NASA Astrophysics Data System (ADS)
Yamaguchi, Takahiro; Takehara, Hiroaki; Sunaga, Yoshinori; Haruta, Makito; Motoyama, Mayumi; Ohta, Yasumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun
2016-04-01
A self-reset pixel of 15 × 15 µm2 with high signal-to-noise ratio (effective peak SNR ≃64 dB) for an implantable image sensor has been developed for intrinsic signal detection arising from hemodynamic responses in a living mouse brain. For detecting local conversion between oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in brain tissues, an implantable imaging device was fabricated with our newly designed self-reset image sensor and orange light-emitting diodes (LEDs; λ = 605 nm). We demonstrated imaging of hemodynamic responses in the sensory cortical area accompanied by forelimb stimulation of a living mouse. The implantable imaging device for intrinsic signal detection is expected to be a powerful tool to measure brain activities in living animals used in behavioral analysis.
-
Lu, Jun-Feng; Zhang, Han; Wu, Jin-Song; Yao, Cheng-Jun; Zhuang, Dong-Xiao; Qiu, Tian-Ming; Jia, Wen-Bin; Mao, Ying; Zhou, Liang-Fu
2012-01-01
As a promising noninvasive imaging technique, functional MRI (fMRI) has been extensively adopted as a functional localization procedure for surgical planning. However, the information provided by preoperative fMRI (pre-fMRI) is hampered by the brain deformation that is secondary to surgical procedures. Therefore, intraoperative fMRI (i-fMRI) becomes a potential alternative that can compensate for brain shifts by updating the functional localization information during craniotomy. However, previous i-fMRI studies required that patients be under general anesthesia, preventing the wider application of such a technique as the patients cannot perform tasks unless they are awake. In this study, we propose a new technique that combines awake surgery and i-fMRI, named “awake” i-fMRI (ai-fMRI). We introduced ai-fMRI to the real-time localization of sensorimotor areas during awake craniotomy in seven patients. The results showed that ai-fMRI could successfully detect activations in the bilateral primary sensorimotor areas and supplementary motor areas for all patients, indicating the feasibility of this technique in eloquent area localization. The reliability of ai-fMRI was further validated using intraoperative stimulation mapping (ISM) in two of the seven patients. Comparisons between the pre-fMRI-derived localization result and the ai-fMRI derived result showed that the former was subject to a heavy brain shift and led to incorrect localization, while the latter solved that problem. Additionally, the approaches for the acquisition and processing of the ai-fMRI data were fully illustrated and described. Some practical issues on employing ai-fMRI in awake craniotomy were systemically discussed, and guidelines were provided. PMID:24179766
-
Bortfeld, M; Rius, M; König, J; Herold-Mende, C; Nies, A T; Keppler, D
2006-01-01
Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.