Neural correlates of motor-cognitive dual-tasking in young and old adults

PubMed Central

Papegaaij, Selma; Hortobágyi, Tibor; Godde, Ben; Kaan, Wim A.; Erhard, Peter; Voelcker-Rehage, Claudia

2017-01-01

When two tasks are performed simultaneously, performance often declines in one or both tasks. These so-called dual-task costs are more pronounced in old than in young adults. One proposed neurological mechanism of the dual-task costs is that old compared with young adults tend to execute single-tasks with higher brain activation. In the brain regions that are needed for both tasks, the reduced residual capacity may interfere with performance of the dual-task. This competition for shared brain regions has been called structural interference. The purpose of the study was to determine whether structural interference indeed plays a role in the age-related decrease in dual-task performance. Functional magnetic resonance imaging (fMRI) was used to investigate 23 young adults (20–29 years) and 32 old adults (66–89 years) performing a calculation (serial subtraction by seven) and balance-simulation (plantar flexion force control) task separately or simultaneously. Behavioral performance decreased during the dual-task compared with the single-tasks in both age groups, with greater dual-task costs in old compared with young adults. Brain activation was significantly higher in old than young adults during all conditions. Region of interest analyses were performed on brain regions that were active in both tasks. Structural interference was apparent in the right insula, as quantified by an age-related reduction in upregulation of brain activity from single- to dual-task. However, the magnitude of upregulation did not correlate with dual-task costs. Therefore, we conclude that the greater dual-task costs in old adults were probably not due to increased structural interference. PMID:29220349

Processing demands upon cognitive, linguistic, and articulatory functions promote grey matter plasticity in the adult multilingual brain: Insights from simultaneous interpreters.

PubMed

Elmer, Stefan; Hänggi, Jürgen; Jäncke, Lutz

2014-05-01

Until now, considerable effort has been made to determine structural brain characteristics related to exceptional multilingual skills. However, at least one important question has not yet been satisfactorily addressed in the previous literature, namely whether and to which extent the processing demands upon cognitive, linguistic, and articulatory functions may promote grey matter plasticity in the adult multilingual brain. Based on the premise that simultaneous interpretation is a highly demanding linguistic task that places strong demands on executive and articulatory functions, here we compared grey matter volumes between professional simultaneous interpreters (SI) and multilingual control subjects. Thereby, we focused on a specific set of a-priori defined bilateral brain regions that have previously been shown to support neurocognitional aspects of language control and linguistic functions in the multilingual brain. These regions are the cingulate gyrus, caudate nucleus, frontal operculum (pars triangularis and opercularis), inferior parietal lobe (IPL) (supramarginal and angular gyrus), and the insula. As a main result, we found reduced grey matter volumes in professional SI, compared to multilingual controls, in the left middle-anterior cingulate gyrus, bilateral pars triangularis, left pars opercularis, bilateral middle part of the insula, and in the left supramarginal gyrus (SMG). Interestingly, grey matter volume in left pars triangularis, right pars opercularis, middle-anterior cingulate gyrus, and in the bilateral caudate nucleus was negatively correlated with the cumulative number of interpreting hours. Hence, we provide first evidence for an expertise-related grey matter architecture that may reflect a composite of brain characteristics that were still present before interpreting training and training-related changes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback.

PubMed

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-05-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback

PubMed Central

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-01-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

Local activity determines functional connectivity in the resting human brain: a simultaneous FDG-PET/fMRI study.

PubMed

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.

Fiberless multicolor neural optoelectrode for in vivo circuit analysis.

PubMed

Kampasi, Komal; Stark, Eran; Seymour, John; Na, Kyounghwan; Winful, Herbert G; Buzsáki, György; Wise, Kensall D; Yoon, Euisik

2016-08-03

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.

Spatiotemporal Distribution of β-Amyloid in Alzheimer Disease Is the Result of Heterogeneous Regional Carrying Capacities.

PubMed

Whittington, Alex; Sharp, David J; Gunn, Roger N

2018-05-01

β-amyloid (Aβ) accumulation in the brain is 1 of 2 pathologic hallmarks of Alzheimer disease (AD), and the spatial distribution of Aβ has been studied extensively ex vivo. Methods: We applied mathematical modeling to Aβ in vivo PET imaging data to investigate competing theories of Aβ spread in AD. Results: Our results provided evidence that Aβ accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is due to heterogeneous regional carrying capacities (regional maximum possible concentration of Aβ) for the aggregated protein rather than to longer-term spreading from seed regions. Conclusion: The in vivo spatiotemporal distribution of Aβ in AD can be mathematically modeled using a logistic growth model in which the Aβ carrying capacity is heterogeneous across the brain but the exponential growth rate and time of half maximal Aβ concentration are constant. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

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

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain

PubMed Central

Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

2014-01-01

The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm3 for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously. PMID:24498247

Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation

PubMed Central

Oswal, Ashwini; Jha, Ashwani; Neal, Spencer; Reid, Alphonso; Bradbury, David; Aston, Peter; Limousin, Patricia; Foltynie, Tom; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

2016-01-01

Background Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. New method In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. Results Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. Comparison with existing approaches To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS. PMID:26698227

Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception

PubMed Central

de Gelder, B.

2016-01-01

The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. PMID:27025242

Regional Slow Waves and Spindles in Human Sleep

PubMed Central

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

A User-Configurable Headstage for Multimodality Neuromonitoring in Freely Moving Rats

PubMed Central

Limnuson, Kanokwan; Narayan, Raj K.; Chiluwal, Amrit; Golanov, Eugene V.; Bouton, Chad E.; Li, Chunyan

2016-01-01

Multimodal monitoring of brain activity, physiology, and neurochemistry is an important approach to gain insight into brain function, modulation, and pathology. With recent progress in micro- and nanotechnology, micro-nano-implants have become important catalysts in advancing brain research. However, to date, only a limited number of brain parameters have been measured simultaneously in awake animals in spite of significant recent progress in sensor technology. Here we have provided a cost and time effective approach to designing a headstage to conduct a multimodality brain monitoring in freely moving animals. To demonstrate this method, we have designed a user-configurable headstage for our micromachined multimodal neural probe. The headstage can reliably record direct-current electrocorticography (DC-ECoG), brain oxygen tension (PbrO2), cortical temperature, and regional cerebral blood flow (rCBF) simultaneously without significant signal crosstalk or movement artifacts for 72 h. Even in a noisy environment, it can record low-level neural signals with high quality. Moreover, it can easily interface with signal conditioning circuits that have high power consumption and are difficult to miniaturize. To the best of our knowledge, this is the first time where multiple physiological, biochemical, and electrophysiological cerebral variables have been simultaneously recorded from freely moving rats. We anticipate that the developed system will aid in gaining further insight into not only normal cerebral functioning but also pathophysiology of conditions such as epilepsy, stroke, and traumatic brain injury. PMID:27594826

Increased phase synchronization during continuous face integration measured simultaneously with EEG and fMRI.

PubMed

Kottlow, Mara; Jann, Kay; Dierks, Thomas; Koenig, Thomas

2012-08-01

Gamma zero-lag phase synchronization has been measured in the animal brain during visual binding. Human scalp EEG studies used a phase locking factor (trial-to-trial phase-shift consistency) or gamma amplitude to measure binding but did not analyze common-phase signals so far. This study introduces a method to identify networks oscillating with near zero-lag phase synchronization in human subjects. We presented unpredictably moving face parts (NOFACE) which - during some periods - produced a complete schematic face (FACE). The amount of zero-lag phase synchronization was measured using global field synchronization (GFS). GFS provides global information on the amount of instantaneous coincidences in specific frequencies throughout the brain. Gamma GFS was increased during the FACE condition. To localize the underlying areas, we correlated gamma GFS with simultaneously recorded BOLD responses. Positive correlates comprised the bilateral middle fusiform gyrus and the left precuneus. These areas may form a network of areas transiently synchronized during face integration, including face-specific as well as binding-specific regions and regions for visual processing in general. Thus, the amount of zero-lag phase synchronization between remote regions of the human visual system can be measured with simultaneously acquired EEG/fMRI. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Fiberless multicolor neural optoelectrode for in vivo circuit analysis

PubMed Central

Kampasi, Komal; Stark, Eran; Seymour, John; Na, Kyounghwan; Winful, Herbert G.; Buzsáki, György; Wise, Kensall D.; Yoon, Euisik

2016-01-01

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets. PMID:27485264

Selective attention to temporal features on nested time scales.

PubMed

Henry, Molly J; Herrmann, Björn; Obleser, Jonas

2015-02-01

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Simultaneous Determination of Vinpocetine and its Major Active Metabolite Apovincaminic Acid in Rats by UPLC-MS/MS and its Application to the Brain Tissue Distribution Study.

PubMed

Wang, Manman; Wang, Lijuan; Sun, Jinghan; Zhang, Lili; Zhao, Longshan; Xiong, Zhili

2018-03-01

A specific, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for simultaneous determination of vinpocetine (VP) and its active metabolite, apovincaminic acid (AVA) in rat brain regions, such as hypothalamus, striatum, cortex, cerebellum and hippocampus. Phenacetin was used as internal standard (IS). Brain tissue samples were precipitated protein by using 500 μL methanol. The separation was achieved on a Waters ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm), using a methanol-water gradient elution at the flow rate of 0.20 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via positive electrospray ionization source (ESI). The quantification was operated using the transitions of m/z 351 → m/z 280 for VP, m/z 323 → m/z 280 for AVA and m/z 180 → m/z 110 for IS, respectively. The calibration curve was linear in concentration range from 0.100 to 60.0 ng/mL for VP and 0.103 to 6.18 ng/mL for AVA. The intra-day and inter-day precision (relative standard deviation, RSD) values were within 11.8%, the accuracy (relative error, RE) was from -1.7% to 3.0% for VP and 2.7% to 9.5% for AVA at all the three concentration levels of quality-control (QC) samples. The improved UPLC-MS/MS method was specific, rapid and sensitive, which was further successfully applied to simultaneous determination of VP and AVA in different rat brain regions after intragastric administration of 4 mg/kg VP. It was indicated that VP could be eliminated quickly in brain, while the elimination of AVA was slow and it could be maintained for more than 12 h in brain. Moreover, it was found that the contents of VP and AVA were much higher in the hypothalamus, striatum and cortex than those in the cerebellum and hippocampus, which verified the distribution characteristics of VP and AVA in different brain regions from the point of quantitation in rats.

Optimized beamforming for simultaneous MEG and intracranial local field potential recordings in deep brain stimulation patients.

PubMed

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.

Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.

PubMed

Banerjee, Abhirup; Maji, Pradipta

2015-12-01

The segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

PubMed

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.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

PubMed Central

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

Hyperglycemia is associated with simultaneous alterations in electrical brain activity in youths with type 1 diabetes mellitus.

PubMed

Rachmiel, M; Cohen, M; Heymen, E; Lezinger, M; Inbar, D; Gilat, S; Bistritzer, T; Leshem, G; Kan-Dror, E; Lahat, E; Ekstein, D

2016-02-01

To assess the association between hyperglycemia and electrical brain activity in type 1 diabetes mellitus (T1DM). Nine youths with T1DM were monitored simultaneously and continuously by EEG and continuous glucose monitor system, for 40 h. EEG powers of 0.5-80 Hz frequency bands in all the different brain regions were analyzed according to interstitial glucose concentration (IGC) ranges of 4-11 mmol/l, 11-15.5 mmol/l and >15.5 mmol/l. Analysis of variance was used to examine the differences in EEG power of each frequency band between the subgroups of IGC. Analysis was performed separately during wakefulness and sleep, controlling for age, gender and HbA1c. Mean IGC was 11.49 ± 5.26 mmol/l in 1253 combined measurements. IGC>15.5 mmol/l compared to 4-11 mmol/l was associated during wakefulness with increased EEG power of low frequencies and with decreased EEG power of high frequencies. During sleep, it was associated with increased EEG power of low frequencies in all brain areas and of high frequencies in frontal and central areas. Asymptomatic transient hyperglycemia in youth with T1DM is associated with simultaneous alterations in electrical brain activity during wakefulness and sleep. The clinical implications of immediate electrical brain alterations under hyperglycemia need to be studied and may lead to adaptations of management. Copyright © 2015. Published by Elsevier Ireland Ltd.

Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception.

PubMed

de Borst, A W; de Gelder, B

2016-08-01

The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Transcranial focused ultrasound stimulation of human primary visual cortex

NASA Astrophysics Data System (ADS)

Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

2016-09-01

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Statistical Analyses of Brain Surfaces Using Gaussian Random Fields on 2-D Manifolds

PubMed Central

Staib, Lawrence H.; Xu, Dongrong; Zhu, Hongtu; Peterson, Bradley S.

2008-01-01

Interest in the morphometric analysis of the brain and its subregions has recently intensified because growth or degeneration of the brain in health or illness affects not only the volume but also the shape of cortical and subcortical brain regions, and new image processing techniques permit detection of small and highly localized perturbations in shape or localized volume, with remarkable precision. An appropriate statistical representation of the shape of a brain region is essential, however, for detecting, localizing, and interpreting variability in its surface contour and for identifying differences in volume of the underlying tissue that produce that variability across individuals and groups of individuals. Our statistical representation of the shape of a brain region is defined by a reference region for that region and by a Gaussian random field (GRF) that is defined across the entire surface of the region. We first select a reference region from a set of segmented brain images of healthy individuals. The GRF is then estimated as the signed Euclidean distances between points on the surface of the reference region and the corresponding points on the corresponding region in images of brains that have been coregistered to the reference. Correspondences between points on these surfaces are defined through deformations of each region of a brain into the coordinate space of the reference region using the principles of fluid dynamics. The warped, coregistered region of each subject is then unwarped into its native space, simultaneously bringing into that space the map of corresponding points that was established when the surfaces of the subject and reference regions were tightly coregistered. The proposed statistical description of the shape of surface contours makes no assumptions, other than smoothness, about the shape of the region or its GRF. The description also allows for the detection and localization of statistically significant differences in the shapes of the surfaces across groups of subjects at both a fine and coarse scale. We demonstrate the effectiveness of these statistical methods by applying them to study differences in shape of the amygdala and hippocampus in a large sample of normal subjects and in subjects with attention deficit/hyperactivity disorder (ADHD). PMID:17243583

Subthalamic nucleus long-range synchronization—an independent hallmark of human Parkinson's disease

PubMed Central

Moshel, Shay; Shamir, Reuben R.; Raz, Aeyal; de Noriega, Fernando R.; Eitan, Renana; Bergman, Hagai; Israel, Zvi

2013-01-01

Beta-band synchronous oscillations in the dorsolateral region of the subthalamic nucleus (STN) of human patients with Parkinson's disease (PD) have been frequently reported. However, the correlation between STN oscillations and synchronization has not been thoroughly explored. The simultaneous recordings of 2390 multi-unit pairs recorded by two parallel microelectrodes (separated by fixed distance of 2 mm, n = 72 trajectories with two electrode tracks >4 mm STN span) in 57 PD patients undergoing STN deep brain stimulation surgery were analyzed. Automatic procedures were utilized to divide the STN into dorsolateral oscillatory and ventromedial non-oscillatory regions, and to quantify the intensity of STN oscillations and synchronicity. Finally, the synchronicity of simultaneously vs. non-simultaneously recorded pairs were compared using a shuffling procedure. Synchronization was observed predominately in the beta range and only between multi-unit pairs in the dorsolateral oscillatory region (n = 615). In paired recordings between sites in the dorsolateral and ventromedial (n = 548) and ventromedial-ventromedial region pairs (n = 1227), no synchronization was observed. Oscillation and synchronicity intensity decline along the STN dorsolateral-ventromedial axis suggesting a fuzzy border between the STN regions. Synchronization strength was significantly correlated to the oscillation power, but synchronization was no longer observed following shuffling. We conclude that STN long-range beta oscillatory synchronization is due to increased neuronal coupling in the Parkinsonian brain and does not merely reflect the outcome of oscillations at similar frequency. The neural synchronization in the dorsolateral (probably the motor domain) STN probably augments the pathological changes in firing rate and patterns of subthalamic neurons in PD patients. PMID:24312018

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

PubMed Central

Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

Network Configurations in the Human Brain Reflect Choice Bias during Rapid Face Processing.

PubMed

Tu, Tao; Schneck, Noam; Muraskin, Jordan; Sajda, Paul

2017-12-13

Network interactions are likely to be instrumental in processes underlying rapid perception and cognition. Specifically, high-level and perceptual regions must interact to balance pre-existing models of the environment with new incoming stimuli. Simultaneous electroencephalography (EEG) and fMRI (EEG/fMRI) enables temporal characterization of brain-network interactions combined with improved anatomical localization of regional activity. In this paper, we use simultaneous EEG/fMRI and multivariate dynamical systems (MDS) analysis to characterize network relationships between constitute brain areas that reflect a subject's choice for a face versus nonface categorization task. Our simultaneous EEG and fMRI analysis on 21 human subjects (12 males, 9 females) identifies early perceptual and late frontal subsystems that are selective to the categorical choice of faces versus nonfaces. We analyze the interactions between these subsystems using an MDS in the space of the BOLD signal. Our main findings show that differences between face-choice and house-choice networks are seen in the network interactions between the early and late subsystems, and that the magnitude of the difference in network interaction positively correlates with the behavioral false-positive rate of face choices. We interpret this to reflect the role of saliency and expectations likely encoded in frontal "late" regions on perceptual processes occurring in "early" perceptual regions. SIGNIFICANCE STATEMENT Our choices are affected by our biases. In visual perception and cognition such biases can be commonplace and quite curious-e.g., we see a human face when staring up at a cloud formation or down at a piece of toast at the breakfast table. Here we use multimodal neuroimaging and dynamical systems analysis to measure whole-brain spatiotemporal dynamics while subjects make decisions regarding the type of object they see in rapidly flashed images. We find that the degree of interaction in these networks accounts for a substantial fraction of our bias to see faces. In general, our findings illustrate how the properties of spatiotemporal networks yield insight into the mechanisms of how we form decisions. Copyright © 2017 the authors 0270-6474/17/3712226-12$15.00/0.

Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

PubMed Central

Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

2016-01-01

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

In Vivo Comparison of Norepinephrine and Dopamine Release in Rat Brain by Simultaneous Measurements with Fast-Scan Cyclic Voltammetry

PubMed Central

Park, Jinwoo; Takmakov, Pavel; Wightman, R. Mark

2011-01-01

Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. Here, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry (FSCV) at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle (VNB), the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra (VTA/SN), the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode FSCV technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures. PMID:21933188

Low Dose Isoflurane Exerts Opposing Effects on Neuronal Network Excitability in Neocortex and Hippocampus

PubMed Central

Ranft, Andreas; von Meyer, Ludwig; Zieglgänsberger, Walter; Kochs, Eberhard; Dodt, Hans-Ulrich

2012-01-01

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity. PMID:22723999

Estimation of effective brain connectivity with dual Kalman filter and EEG source localization methods.

PubMed

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.

Development of a multichannel optical system for differential cortical measurement

NASA Astrophysics Data System (ADS)

Maki, Atsushi; Yamashita, Yuichi; Watanabe, Eiju; Koizumi, Hideaki

1997-08-01

A prototype system based on intensity-modulation spectroscopy (IMS) was produced with the goal of developing 'optoencephalography' as a new instrument for clinical application and for investigating human brain functions. This system can use dual wavelengths (787 and 827 nm) to simultaneously measure reflectances at 8 measurement positions on the human head. Using the system, we measured the changes in blood circulation and oxygenation changes caused by epileptic seizures and specific brain functions. The former measurements were made simultaneously with tests to determine the epileptic focus by using single-photon-emission computed tomography (SPECT) and electrodes set in the brian. Four measurement positions were fixed in each temporal region. The areas where cerebral blood flow increased, as observed by SPECT, corresponded to the positions where the regional cerebral blood volume (rCBV) increased, as measured by the IMS system. Furthermore, the timing of the epileptic seizures, as measured by the depth-electrodes, corresponded to the timing of the increase in rCBV measured by the prototype system. Our measurements of changes in blood circulation as a result of brain functions were made for motor functions to compare the differences between the right and left hemisphere in how they respond to specific functions. Four measurement positions were set in bilateral motor areas. Significant differences in blood circulation in connection with brain activities were observed between the right and left hemispheres.

Varieties of semantic cognition revealed through simultaneous decomposition of intrinsic brain connectivity and behaviour.

PubMed

Vatansever, Deniz; Bzdok, Danilo; Wang, Hao-Ting; Mollo, Giovanna; Sormaz, Mladen; Murphy, Charlotte; Karapanagiotidis, Theodoros; Smallwood, Jonathan; Jefferies, Elizabeth

2017-09-01

Contemporary theories assume that semantic cognition emerges from a neural architecture in which different component processes are combined to produce aspects of conceptual thought and behaviour. In addition to the state-level, momentary variation in brain connectivity, individuals may also differ in their propensity to generate particular configurations of such components, and these trait-level differences may relate to individual differences in semantic cognition. We tested this view by exploring how variation in intrinsic brain functional connectivity between semantic nodes in fMRI was related to performance on a battery of semantic tasks in 154 healthy participants. Through simultaneous decomposition of brain functional connectivity and semantic task performance, we identified distinct components of semantic cognition at rest. In a subsequent validation step, these data-driven components demonstrated explanatory power for neural responses in an fMRI-based semantic localiser task and variation in self-generated thoughts during the resting-state scan. Our findings showed that good performance on harder semantic tasks was associated with relative segregation at rest between frontal brain regions implicated in controlled semantic retrieval and the default mode network. Poor performance on easier tasks was linked to greater coupling between the same frontal regions and the anterior temporal lobe; a pattern associated with deliberate, verbal thematic thoughts at rest. We also identified components that related to qualities of semantic cognition: relatively good performance on pictorial semantic tasks was associated with greater separation of angular gyrus from frontal control sites and greater integration with posterior cingulate and anterior temporal cortex. In contrast, good speech production was linked to the separation of angular gyrus, posterior cingulate and temporal lobe regions. Together these data show that quantitative and qualitative variation in semantic cognition across individuals emerges from variations in the interaction of nodes within distinct functional brain networks. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural brain connectivity and cognitive ability differences: A multivariate distance matrix regression analysis.

PubMed

Ponsoda, Vicente; Martínez, Kenia; Pineda-Pardo, José A; Abad, Francisco J; Olea, Julio; Román, Francisco J; Barbey, Aron K; Colom, Roberto

2017-02-01

Neuroimaging research involves analyses of huge amounts of biological data that might or might not be related with cognition. This relationship is usually approached using univariate methods, and, therefore, correction methods are mandatory for reducing false positives. Nevertheless, the probability of false negatives is also increased. Multivariate frameworks have been proposed for helping to alleviate this balance. Here we apply multivariate distance matrix regression for the simultaneous analysis of biological and cognitive data, namely, structural connections among 82 brain regions and several latent factors estimating cognitive performance. We tested whether cognitive differences predict distances among individuals regarding their connectivity pattern. Beginning with 3,321 connections among regions, the 36 edges better predicted by the individuals' cognitive scores were selected. Cognitive scores were related to connectivity distances in both the full (3,321) and reduced (36) connectivity patterns. The selected edges connect regions distributed across the entire brain and the network defined by these edges supports high-order cognitive processes such as (a) (fluid) executive control, (b) (crystallized) recognition, learning, and language processing, and (c) visuospatial processing. This multivariate study suggests that one widespread, but limited number, of regions in the human brain, supports high-level cognitive ability differences. Hum Brain Mapp 38:803-816, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

2017-10-01

Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

Neurophysiological Factors in Human Information Processing Capacity

ERIC Educational Resources Information Center

Ramsey, Nick F.; Jansma, J. M.; Jager, G.; Van Raalten, T.; Kahn, R. S.

2004-01-01

What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of…

Divided versus selective attention: evidence for common processing mechanisms

PubMed Central

Hahn, Britta; Wolkenberg, Frank A.; Ross, Thomas J.; Myers, Carol S.; Heishman, Stephen J.; Stein, Dan J.; Kurup, Pradeep K.; Stein, Elliot A.

2008-01-01

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks’ processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants’ BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention. PMID:18479670

Divided versus selective attention: evidence for common processing mechanisms.

PubMed

Hahn, Britta; Wolkenberg, Frank A; Ross, Thomas J; Myers, Carol S; Heishman, Stephen J; Stein, Dan J; Kurup, Pradeep K; Stein, Elliot A

2008-06-18

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention.

Simultaneous imaging of oxygen tension and blood flow in animals using a digital micromirror device.

PubMed

Ponticorvo, Adrien; Dunn, Andrew K

2010-04-12

In this study we present a novel imaging method that combines high resolution cerebral blood flow imaging with a highly flexible map of absolute pO(2). In vivo measurements of pO(2) in animals using phosphorescence quenching is a well established method, and is preferable over electrical probes which are inherently invasive and are limited to single point measurements. However, spatially resolved pO(2) measurements using phosphorescence lifetime quenching typically require expensive cameras to obtain images of pO(2) and often suffer from poor signal to noise. Our approach enables us to retain the high temporal resolution and sensitivity of single point detection of phosphorescence by using a digital micromirror device (DMD) to selectively illuminate arbitrarily shaped regions of tissue. In addition, by simultaneously using Laser Speckle Contrast Imaging (LSCI) to measure relative blood flow, we can better examine the relationship between blood flow and absolute pO(2). We successfully used this instrument to study changes that occur during ischemic conditions in the brain with enough spatial resolution to clearly distinguish different regions. This novel instrument will provide researchers with an inexpensive and improved technique to examine multiple hemodynamic parameters simultaneously in the brain as well as other tissues.

Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment.

PubMed

Tosun, Duygu; Schuff, Norbert; Mathis, Chester A; Jagust, William; Weiner, Michael W

2011-04-01

Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by (11)C-labelled Pittsburgh compound B positron emission tomography imaging. However, some individuals tolerate high brain amyloid-β loads without developing symptoms, while others progressively decline, suggesting that events in the brain downstream from amyloid-β deposition, such as regional brain atrophy rates, play an important role. The main purpose of this study was to understand the relationship between the regional distributions of increased amyloid-β and the regional distribution of increased brain atrophy rates in patients with mild cognitive impairment. To simultaneously capture the spatial distributions of amyloid-β and brain atrophy rates, we employed the statistical concept of parallel independent component analysis, an effective method for joint analysis of multimodal imaging data. Parallel independent component analysis identified significant relationships between two patterns of amyloid-β deposition and atrophy rates: (i) increased amyloid-β burden in the left precuneus/cuneus and medial-temporal regions was associated with increased brain atrophy rates in the left medial-temporal and parietal regions; and (ii) in contrast, increased amyloid-β burden in bilateral precuneus/cuneus and parietal regions was associated with increased brain atrophy rates in the right medial temporal regions. The spatial distribution of increased amyloid-β and the associated spatial distribution of increased brain atrophy rates embrace a characteristic pattern of brain structures known for a high vulnerability to Alzheimer's disease pathology, encouraging for the use of (11)C-labelled Pittsburgh compound B positron emission tomography measures as early indicators of Alzheimer's disease. These results may begin to shed light on the mechanisms by which amyloid-β deposition leads to neurodegeneration and cognitive decline and the development of a more specific Alzheimer's disease-specific imaging signature for diagnosis and use of this knowledge in the development of new anti-therapies for Alzheimer's disease.

Injured Brains and Adaptive Networks: The Benefits and Costs of Hyperconnectivity.

PubMed

Hillary, Frank G; Grafman, Jordan H

2017-05-01

A common finding in human functional brain-imaging studies is that damage to neural systems paradoxically results in enhanced functional connectivity between network regions, a phenomenon commonly referred to as 'hyperconnectivity'. Here, we describe the various ways that hyperconnectivity operates to benefit a neural network following injury while simultaneously negotiating the trade-off between metabolic cost and communication efficiency. Hyperconnectivity may be optimally expressed by increasing connections through the most central and metabolically efficient regions (i.e., hubs). While adaptive in the short term, we propose that chronic hyperconnectivity may leave network hubs vulnerable to secondary pathological processes over the life span due to chronically elevated metabolic stress. We conclude by offering novel, testable hypotheses for advancing our understanding of the role of hyperconnectivity in systems-level brain plasticity in neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

An EEG Finger-Print of fMRI deep regional activation.

PubMed

Meir-Hasson, Yehudit; Kinreich, Sivan; Podlipsky, Ilana; Hendler, Talma; Intrator, Nathan

2014-11-15

This work introduces a general framework for producing an EEG Finger-Print (EFP) which can be used to predict specific brain activity as measured by fMRI at a given deep region. This new approach allows for improved EEG spatial resolution based on simultaneous fMRI activity measurements. Advanced signal processing and machine learning methods were applied on EEG data acquired simultaneously with fMRI during relaxation training guided by on-line continuous feedback on changing alpha/theta EEG measure. We focused on demonstrating improved EEG prediction of activation in sub-cortical regions such as the amygdala. Our analysis shows that a ridge regression model that is based on time/frequency representation of EEG data from a single electrode, can predict the amygdala related activity significantly better than a traditional theta/alpha activity sampled from the best electrode and about 1/3 of the times, significantly better than a linear combination of frequencies with a pre-defined delay. The far-reaching goal of our approach is to be able to reduce the need for fMRI scanning for probing specific sub-cortical regions such as the amygdala as the basis for brain-training procedures. On the other hand, activity in those regions can be characterized with higher temporal resolution than is obtained by fMRI alone thus revealing additional information about their processing mode. Copyright © 2013 Elsevier Inc. All rights reserved.

Interpretation of the Precision Matrix and Its Application in Estimating Sparse Brain Connectivity during Sleep Spindles from Human Electrocorticography Recordings

PubMed Central

Das, Anup; Sampson, Aaron L.; Lainscsek, Claudia; Muller, Lyle; Lin, Wutu; Doyle, John C.; Cash, Sydney S.; Halgren, Eric; Sejnowski, Terrence J.

2017-01-01

The correlation method from brain imaging has been used to estimate functional connectivity in the human brain. However, brain regions might show very high correlation even when the two regions are not directly connected due to the strong interaction of the two regions with common input from a third region. One previously proposed solution to this problem is to use a sparse regularized inverse covariance matrix or precision matrix (SRPM) assuming that the connectivity structure is sparse. This method yields partial correlations to measure strong direct interactions between pairs of regions while simultaneously removing the influence of the rest of the regions, thus identifying regions that are conditionally independent. To test our methods, we first demonstrated conditions under which the SRPM method could indeed find the true physical connection between a pair of nodes for a spring-mass example and an RC circuit example. The recovery of the connectivity structure using the SRPM method can be explained by energy models using the Boltzmann distribution. We then demonstrated the application of the SRPM method for estimating brain connectivity during stage 2 sleep spindles from human electrocorticography (ECoG) recordings using an 8 × 8 electrode array. The ECoG recordings that we analyzed were from a 32-year-old male patient with long-standing pharmaco-resistant left temporal lobe complex partial epilepsy. Sleep spindles were automatically detected using delay differential analysis and then analyzed with SRPM and the Louvain method for community detection. We found spatially localized brain networks within and between neighboring cortical areas during spindles, in contrast to the case when sleep spindles were not present. PMID:28095202

Simultaneous measurement of brain tissue oxygen partial pressure, temperature, and global oxygen consumption during hibernation, arousal, and euthermy in non-sedated and non-anesthetized Arctic ground squirrels.

PubMed

Ma, Yilong; Wu, Shufen

2008-09-30

This study reports an online temperature correction method for determining tissue oxygen partial pressure P(tO2) in the striatum and a novel simultaneous measurement of brain P(tO2) and temperature (T(brain)) in conjunction with global oxygen consumption V(O2) in non-sedated and non-anesthetized freely moving Arctic ground squirrels (AGS, Spermophilus parryii). This method fills an important research gap-the lack of a suitable method for physiologic studies of tissue P(O2) in hibernating or other cool-blooded species. P(tO2) in AGS brain during euthermy (21.22+/-2.06 mmHg) is significantly higher (P=0.016) than during hibernation (13.21+/-0.46 mmHg) suggests brain oxygenation in the striatum is normoxic during euthermy and hypoxic during hibernation. These results in P(tO2) are different from blood oxygen partial pressure P(aO2) in AGS, which are significantly lower during euthermy than during hibernation and are actually hypoxic during euthermy and normoxic during hibernation in our previous study. This intriguing difference between the P(O2) of brain tissue and blood during these two physiological states suggests that regional mechanisms in the brain play a role in maintaining tissue oxygenation and protect against hypoxia during hibernation.

The two-brain approach: how can mutually interacting brains teach us something about social interaction?

PubMed Central

Konvalinka, Ivana; Roepstorff, Andreas

2012-01-01

Measuring brain activity simultaneously from two people interacting is intuitively appealing if one is interested in putative neural markers of social interaction. However, given the complex nature of interactions, it has proven difficult to carry out two-person brain imaging experiments in a methodologically feasible and conceptually relevant way. Only a small number of recent studies have put this into practice, using fMRI, EEG, or NIRS. Here, we review two main two-brain methodological approaches, each with two conceptual strategies. The first group has employed two-brain fMRI recordings, studying (1) turn-based interactions on the order of seconds, or (2) pseudo-interactive scenarios, where only one person is scanned at a time, investigating the flow of information between brains. The second group of studies has recorded dual EEG/NIRS from two people interacting, in (1) face-to-face turn-based interactions, investigating functional connectivity between theory-of-mind regions of interacting partners, or in (2) continuous mutual interactions on millisecond timescales, to measure coupling between the activity in one person's brain and the activity in the other's brain. We discuss the questions these approaches have addressed, and consider scenarios when simultaneous two-brain recordings are needed. Furthermore, we suggest that (1) quantification of inter-personal neural effects via measures of emergence, and (2) multivariate decoding models that generalize source-specific features of interaction, may provide novel tools to study brains in interaction. This may allow for a better understanding of social cognition as both representation and participation. PMID:22837744

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Jing; Rocke, David M.; Perry, George

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE PAGES

Xia, Jing; Rocke, David M.; Perry, George; ...

2014-01-01

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Comparison of simultaneously recorded [H2(15)O]-PET and LORETA during cognitive and pharmacological activation.

PubMed

Gamma, Alex; Lehmann, Dietrich; Frei, Edi; Iwata, Kazuki; Pascual-Marqui, Roberto D; Vollenweider, Franz X

2004-06-01

The complementary strengths and weaknesses of established functional brain imaging methods (high spatial, low temporal resolution) and EEG-based techniques (low spatial, high temporal resolution) make their combined use a promising avenue for studying brain processes at a more fine-grained level. However, this strategy requires a better understanding of the relationship between hemodynamic/metabolic and neuroelectric measures of brain activity. We investigated possible correspondences between cerebral blood flow (CBF) as measured by [H2O]-PET and intracerebral electric activity computed by Low Resolution Brain Electromagnetic Tomography (LORETA) from scalp-recorded multichannel EEG in healthy human subjects during cognitive and pharmacological stimulation. The two imaging modalities were compared by descriptive, correlational, and variance analyses, the latter carried out using statistical parametric mapping (SPM99). Descriptive visual comparison showed a partial overlap between the sets of active brain regions detected by the two modalities. A number of exclusively positive correlations of neuroelectric activity with regional CBF were found across the whole EEG frequency range, including slow wave activity, the latter finding being in contrast to most previous studies conducted in patients. Analysis of variance revealed an extensive lack of statistically significant correspondences between brain activity changes as measured by PET vs. EEG-LORETA. In general, correspondences, to the extent they were found, were dependent on experimental condition, brain region, and EEG frequency. Copyright 2004 Wiley-Liss, Inc.

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

PubMed

Badve, C; Yu, A; Dastmalchian, S; Rogers, M; Ma, D; Jiang, Y; Margevicius, S; Pahwa, S; Lu, Z; Schluchter, M; Sunshine, J; Griswold, M; Sloan, A; Gulani, V

2017-03-01

MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00; P < .0001). MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. © 2017 by American Journal of Neuroradiology.

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study.

PubMed

Dinomais, Mickael; Chinier, Eva; Lignon, Gregoire; Richard, Isabelle; Ter Minassian, Aram; Tich, Sylvie Nguyen The

2013-10-01

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action-observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening-closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more "higher motor areas" including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sexual selection predicts brain structure in dragon lizards.

PubMed

Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

2017-02-01

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Stretchable Transparent Electrode Arrays for Simultaneous Electrical and Optical Interrogation of Neural Circuits in Vivo.

PubMed

Zhang, Jing; Liu, Xiaojun; Xu, Wenjing; Luo, Wenhan; Li, Ming; Chu, Fangbing; Xu, Lu; Cao, Anyuan; Guan, Jisong; Tang, Shiming; Duan, Xiaojie

2018-05-09

Recent developments of transparent electrode arrays provide a unique capability for simultaneous optical and electrical interrogation of neural circuits in the brain. However, none of these electrode arrays possess the stretchability highly desired for interfacing with mechanically active neural systems, such as the brain under injury, the spinal cord, and the peripheral nervous system (PNS). Here, we report a stretchable transparent electrode array from carbon nanotube (CNT) web-like thin films that retains excellent electrochemical performance and broad-band optical transparency under stretching and is highly durable under cyclic stretching deformation. We show that the CNT electrodes record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. Simultaneous two-photon calcium imaging through the transparent CNT electrodes from cortical surfaces of GCaMP-expressing mice with epilepsy shows individual activated neurons in brain regions from which the concurrent electrical recording is taken, thus providing complementary cellular information in addition to the high-temporal-resolution electrical recording. Notably, the studies on rats show that the CNT electrodes remain operational during and after brain contusion that involves the rapid deformation of both the electrode array and brain tissue. This enables real-time, continuous electrophysiological monitoring of cortical activity under traumatic brain injury. These results highlight the potential application of the stretchable transparent CNT electrode arrays in combining electrical and optical modalities to study neural circuits, especially under mechanically active conditions, which could potentially provide important new insights into the local circuit dynamics of the spinal cord and PNS as well as the mechanism underlying traumatic injuries of the nervous system.

Effect of MRI acoustic noise on cerebral fludeoxyglucose uptake in simultaneous MR-PET imaging.

PubMed

Chonde, Daniel B; Abolmaali, Nasreddin; Arabasz, Grae; Guimaraes, Alexander R; Catana, Ciprian

2013-05-01

Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P < 0.05 (corrected) was used; however, a P < 0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]). Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude.

Theta and Alpha Oscillations in Attentional Interaction during Distracted Driving

PubMed Central

Wang, Yu-Kai; Jung, Tzyy-Ping; Lin, Chin-Teng

2018-01-01

Performing multiple tasks simultaneously usually affects the behavioral performance as compared with executing the single task. Moreover, processing multiple tasks simultaneously often involve more cognitive demands. Two visual tasks, lane-keeping task and mental calculation, were utilized to assess the brain dynamics through 32-channel electroencephalogram (EEG) recorded from 14 participants. A 400-ms stimulus onset asynchrony (SOA) factor was used to induce distinct levels of attentional requirements. In the dual-task conditions, the deteriorated behavior reflected the divided attention and the overlapping brain resources used. The frontal, parietal and occipital components were decomposed by independent component analysis (ICA) algorithm. The event- and response-related theta and alpha oscillations in selected brain regions were investigated first. The increased theta oscillation in frontal component and decreased alpha oscillations in parietal and occipital components reflect the cognitive demands and attentional requirements as executing the designed tasks. Furthermore, time-varying interactive over-additive (O-Add), additive (Add) and under-additive (U-Add) activations were explored and summarized through the comparison between the summation of the elicited spectral perturbations in two single-task conditions and the spectral perturbations in the dual task. Add and U-Add activations were observed while executing the dual tasks. U-Add theta and alpha activations dominated the posterior region in dual-task situations. Our results show that both deteriorated behaviors and interactive brain activations should be comprehensively considered for evaluating workload or attentional interaction precisely. PMID:29479310

fMRI reveals reciprocal inhibition between social and physical cognitive domains

PubMed Central

Jack, Anthony I.; Dawson, Abigail; Begany, Katelyn; Leckie, Regina L.; Barry, Kevin; Ciccia, Angela; Snyder, Abraham

2012-01-01

Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which is directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results indicate the reciprocal inhibition is not attributable to constraints inherent in the tasks, but is neural in origin. Hence, there is a physiological constraint on our ability to simultaneously engage two distinct cognitive modes. Further work is needed to more precisely characterize these opposing cognitive domains. PMID:23110882

Understanding in an instant: neurophysiological evidence for mechanistic language circuits in the brain.

PubMed

Pulvermüller, Friedemann; Shtyrov, Yury; Hauk, Olaf

2009-08-01

How long does it take the human mind to grasp the idea when hearing or reading a sentence? Neurophysiological methods looking directly at the time course of brain activity indexes of comprehension are critical for finding the answer to this question. As the dominant cognitive approaches, models of serial/cascaded and parallel processing, make conflicting predictions on the time course of psycholinguistic information access, they can be tested using neurophysiological brain activation recorded in MEG and EEG experiments. Seriality and cascading of lexical, semantic and syntactic processes receives support from late (latency approximately 1/2s) sequential neurophysiological responses, especially N400 and P600. However, parallelism is substantiated by early near-simultaneous brain indexes of a range of psycholinguistic processes, up to the level of semantic access and context integration, emerging already 100-250ms after critical stimulus information is present. Crucially, however, there are reliable latency differences of 20-50ms between early cortical area activations reflecting lexical, semantic and syntactic processes, which are left unexplained by current serial and parallel brain models of language. We here offer a mechanistic model grounded in cortical nerve cell circuits that builds upon neuroanatomical and neurophysiological knowledge and explains both near-simultaneous activations and fine-grained delays. A key concept is that of discrete distributed cortical circuits with specific inter-area topographies. The full activation, or ignition, of specifically distributed binding circuits explains the near-simultaneity of early neurophysiological indexes of lexical, syntactic and semantic processing. Activity spreading within circuits determined by between-area conduction delays accounts for comprehension-related regional activation differences in the millisecond range.

Visual brain activity patterns classification with simultaneous EEG-fMRI: A multimodal approach.

PubMed

Ahmad, Rana Fayyaz; Malik, Aamir Saeed; Kamel, Nidal; Reza, Faruque; Amin, Hafeez Ullah; Hussain, Muhammad

2017-01-01

Classification of the visual information from the brain activity data is a challenging task. Many studies reported in the literature are based on the brain activity patterns using either fMRI or EEG/MEG only. EEG and fMRI considered as two complementary neuroimaging modalities in terms of their temporal and spatial resolution to map the brain activity. For getting a high spatial and temporal resolution of the brain at the same time, simultaneous EEG-fMRI seems to be fruitful. In this article, we propose a new method based on simultaneous EEG-fMRI data and machine learning approach to classify the visual brain activity patterns. We acquired EEG-fMRI data simultaneously on the ten healthy human participants by showing them visual stimuli. Data fusion approach is used to merge EEG and fMRI data. Machine learning classifier is used for the classification purposes. Results showed that superior classification performance has been achieved with simultaneous EEG-fMRI data as compared to the EEG and fMRI data standalone. This shows that multimodal approach improved the classification accuracy results as compared with other approaches reported in the literature. The proposed simultaneous EEG-fMRI approach for classifying the brain activity patterns can be helpful to predict or fully decode the brain activity patterns.

Emotional arousal amplifies the effects of biased competition in the brain

PubMed Central

Lee, Tae-Ho; Sakaki, Michiko; Cheng, Ruth; Velasco, Ricardo

2014-01-01

The arousal-biased competition model predicts that arousal increases the gain on neural competition between stimuli representations. Thus, the model predicts that arousal simultaneously enhances processing of salient stimuli and impairs processing of relatively less-salient stimuli. We tested this model with a simple dot-probe task. On each trial, participants were simultaneously exposed to one face image as a salient cue stimulus and one place image as a non-salient stimulus. A border around the face cue location further increased its bottom-up saliency. Before these visual stimuli were shown, one of two tones played: one that predicted a shock (increasing arousal) or one that did not. An arousal-by-saliency interaction in category-specific brain regions (fusiform face area for salient faces and parahippocampal place area for non-salient places) indicated that brain activation associated with processing the salient stimulus was enhanced under arousal whereas activation associated with processing the non-salient stimulus was suppressed under arousal. This is the first functional magnetic resonance imaging study to demonstrate that arousal can enhance information processing for prioritized stimuli while simultaneously impairing processing of non-prioritized stimuli. Thus, it goes beyond previous research to show that arousal does not uniformly enhance perceptual processing, but instead does so selectively in ways that optimizes attention to highly salient stimuli. PMID:24532703

Modality-specific alpha modulations facilitate long-term memory encoding in the presence of distracters.

PubMed

Jiang, Haiteng; van Gerven, Marcel A J; Jensen, Ole

2015-03-01

It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it reflects the functional disengagement of specific regions in attention and memory tasks. We here ask if such allocation of resources by alpha oscillations generalizes to long-term memory encoding in a cross-modal setting in which we acquired the ongoing brain activity using magnetoencephalography. Participants were asked to encode pictures while ignoring simultaneously presented words and vice versa. We quantified the brain activity during rehearsal reflecting subsequent memory in the different attention conditions. The key finding was that successful long-term memory encoding is reflected by alpha power decreases in the sensory region of the to-be-attended modality and increases in the sensory region of the to-be-ignored modality to suppress distraction during rehearsal period. Our results corroborate related findings from attention studies by demonstrating that alpha activity is also important for the allocation of resources during long-term memory encoding in the presence of distracters.

Neural correlates of trust.

PubMed

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-12-11

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.

Neural correlates of trust

PubMed Central

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-01-01

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species. PMID:18056800

Dwelling quietly in the rich club: brain network determinants of slow cortical fluctuations.

PubMed

Gollo, Leonardo L; Zalesky, Andrew; Hutchison, R Matthew; van den Heuvel, Martijn; Breakspear, Michael

2015-05-19

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously--elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow timescales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding 'feeder' cortical regions shows unstable, rapidly fluctuating dynamics likely to be crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Simultaneous perception of a spoken and a signed language: The brain basis of ASL-English code-blends

PubMed Central

Weisberg, Jill; McCullough, Stephen; Emmorey, Karen

2018-01-01

Code-blends (simultaneous words and signs) are a unique characteristic of bimodal bilingual communication. Using fMRI, we investigated code-blend comprehension in hearing native ASL-English bilinguals who made a semantic decision (edible?) about signs, audiovisual words, and semantically equivalent code-blends. English and ASL recruited a similar fronto-temporal network with expected modality differences: stronger activation for English in auditory regions of bilateral superior temporal cortex, and stronger activation for ASL in bilateral occipitotemporal visual regions and left parietal cortex. Code-blend comprehension elicited activity in a combination of these regions, and no cognitive control regions were additionally recruited. Furthermore, code-blends elicited reduced activation relative to ASL presented alone in bilateral prefrontal and visual extrastriate cortices, and relative to English alone in auditory association cortex. Consistent with behavioral facilitation observed during semantic decisions, the findings suggest that redundant semantic content induces more efficient neural processing in language and sensory regions during bimodal language integration. PMID:26177161

Cerebral hemodynamic responses to seizure in the mouse brain: simultaneous near-infrared spectroscopy-electroencephalography study

NASA Astrophysics Data System (ADS)

Lee, Seungduk; Lee, Mina; Koh, Dalkwon; Kim, Beop-Min; Choi, Jee Hyun

2010-05-01

We applied near-infrared spectroscopy (NIRS) and electroencephalography (EEG) simultaneously on the mouse brain and investigated the hemodynamic response to epileptic episodes under pharmacologically driven seizure. γ-butyrolactone (GBL) and 4-aminopyridine (4-AP) were applied to induce absence and tonic-clonic seizures, respectively. The epileptic episodes were identified from the single-channel EEG, and the corresponding hemodynamic changes in different regions of the brain were characterized by multichannel frequency-domain NIRS. Our results are the following: (i) the oxyhemoglobin level increases in the case of GBL-treated mice but not 4-AP-treated mice compared to the predrug state; (ii) the dominant response to each absence seizure is a decrease in deoxyhemolobin; (iii) the phase shift between oxy- and deoxyhemoglobin reduces in GBL-treated mice but no 4-AP-treated mice; and (iv) the spatial correlation of hemodynamics increased significantly in 4-AP-treated mice but not in GBL-treated mice. Our results shows that spatiotemporal tracking of cerebral hemodynamics using NIRS can be successfully applied to the mouse brain in conjunction with electrophysiological recording, which will support the study of molecular, cellular, and network origin of neurovascular coupling in vivo.

Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

PubMed Central

Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

2013-01-01

The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

EFFECT OF WEARING AN N95 FILTERING FACEPIECE RESPIRATOR ON SUPEROMEDIAL ORBITAL INFRARED INDIRECT BRAIN TEMPERATURE MEASUREMENTS

PubMed Central

DiLeo, Travis; Roberge, Raymond J.; Kim, Jung-Hyun

2016-01-01

Purpose To determine any effect of wearing a filtering facepiece respirator on brain temperature. Methods Subjects (n=18) wore a filtering facepiece respirator (FFR) for 1h at rest while undergoing infrared thermography measurements of the superomedial periobital region of the eye, a non-invasive indirect method of brain temperature measurements we termed the superomedial orbital infrared indirect brain temperature (SOIIBT) measurement. Temperature of the facial skin covered by the FFR, infrared temperature measurements of the tympanic membrane and superficial temporal artery region were concurrently measured, and subjective impressions of thermal comfort obtained simultaneously. Results The temperature of the skin under the FFR and subjective impressions of thermal discomfort both increased significantly. The mean tympanic membrane temperature did not increase, and the superficial temporal artery region temperature decreased significantly. The SOIIBT values did not change significantly, but subjects who switched from nasal to oronasal breathing during the study (n=5) experienced a slight increase in the SOIIBT measurements. Conclusions Wearing a FFR for 1h at rest does not have a significant effect on brain temperatures, as evaluated by the SOIIBT measurements, but a change in the route of breathing may impact these measurements. These findings suggest that subjective impressions of thermal discomfort from wearing a FFR under the study conditions are more likely the result of local dermal sensations rather than brain warming. PMID:26759336

Development of an UPLC-MS/MS method for simultaneous quantitation of 11 d-amino acids in different regions of rat brain: Application to a study on the associations of d-amino acid concentration changes and Alzheimer's disease.

PubMed

Li, Zhe; Xing, Yuping; Guo, Xingjie; Cui, Yan

2017-07-15

There are significant differences in d-amino acid concentrations between healthy people and Alzheimer's disease patients. In order to investigate the potential correlation between d-amino acids and Alzheimer's disease, a simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed. The method was applied to simultaneous determination of 11 d-amino acids in different regions of rat brain. Rat brain homogenates were firstly pretreated with protein precipitation procedure and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]. Baseline separation of the derivatives was achieved on an ACQUITY UPLC BEH C 18 column (2.1 mm×50mm, 1.7μm). The mobile phase consisted of acetonitrile and water (containing 8mM ammonium hydrogen carbonate) and the flow rate was 0.6mLmin -1 . The derived analytes were sensitively detected by multiple reaction monitoring in the positive ion mode. The lower limits of quantitation ranged from 0.06 to 10ngmL -1 with excellent linearity (r≥0.9909). The intra- and inter-day RSD were in the range of 3.6-12% and 5.7-12%, respectively. The recovery rate was 82.5%-95.3%. With this UPLC-MS/MS method, the 11 d-amino acids in hippocampus, cerebral cortex, olfactory bulb and cerebellum from Alzheimer's disease rats and age-matched controls could be simultaneously determined. Compared with the normal controls, the concentrations of d-serine, d-alanine, d-leucine, and d-proline in hippocampus and cerebral cortex of Alzheimer's disease rat brain were significantly decreased, while no differences in olfactory bulb and cerebellum of all the d-amino acids were observed. The different amounts and distribution of d-amino acids in brain between the two groups, which regulated by particular pathological changes of Alzheimer's disease, would give new insights into further study in neuropathogenesis and provide novel therapeutic targets of Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Network Configurations in the Human Brain Reflect Choice Bias during Rapid Face Processing

PubMed Central

Schneck, Noam

2017-01-01

Network interactions are likely to be instrumental in processes underlying rapid perception and cognition. Specifically, high-level and perceptual regions must interact to balance pre-existing models of the environment with new incoming stimuli. Simultaneous electroencephalography (EEG) and fMRI (EEG/fMRI) enables temporal characterization of brain–network interactions combined with improved anatomical localization of regional activity. In this paper, we use simultaneous EEG/fMRI and multivariate dynamical systems (MDS) analysis to characterize network relationships between constitute brain areas that reflect a subject's choice for a face versus nonface categorization task. Our simultaneous EEG and fMRI analysis on 21 human subjects (12 males, 9 females) identifies early perceptual and late frontal subsystems that are selective to the categorical choice of faces versus nonfaces. We analyze the interactions between these subsystems using an MDS in the space of the BOLD signal. Our main findings show that differences between face-choice and house-choice networks are seen in the network interactions between the early and late subsystems, and that the magnitude of the difference in network interaction positively correlates with the behavioral false-positive rate of face choices. We interpret this to reflect the role of saliency and expectations likely encoded in frontal “late” regions on perceptual processes occurring in “early” perceptual regions. SIGNIFICANCE STATEMENT Our choices are affected by our biases. In visual perception and cognition such biases can be commonplace and quite curious—e.g., we see a human face when staring up at a cloud formation or down at a piece of toast at the breakfast table. Here we use multimodal neuroimaging and dynamical systems analysis to measure whole-brain spatiotemporal dynamics while subjects make decisions regarding the type of object they see in rapidly flashed images. We find that the degree of interaction in these networks accounts for a substantial fraction of our bias to see faces. In general, our findings illustrate how the properties of spatiotemporal networks yield insight into the mechanisms of how we form decisions. PMID:29118108

Orbitofrontal cortex mediates pain inhibition by monetary reward.

PubMed

Becker, Susanne; Gandhi, Wiebke; Pomares, Florence; Wager, Tor D; Schweinhardt, Petra

2017-04-01

Pleasurable stimuli, including reward, inhibit pain, but the level of the neuraxis at which they do so and the cerebral processes involved are unknown. Here, we characterized a brain circuitry mediating pain inhibition by reward. Twenty-four healthy participants underwent functional magnetic resonance imaging while playing a wheel of fortune game with simultaneous thermal pain stimuli and monetary wins or losses. As expected, winning decreased pain perception compared to losing. Inter-individual differences in pain modulation by monetary wins relative to losses correlated with activation in the medial orbitofrontal cortex (mOFC). When pain and reward occured simultaneously, mOFCs functional connectivity changed: the signal time course in the mOFC condition-dependent correlated negatively with the signal time courses in the rostral anterior insula, anterior-dorsal cingulate cortex and primary somatosensory cortex, which might signify moment-to-moment down-regulation of these regions by the mOFC. Monetary wins and losses did not change the magnitude of pain-related activation, including in regions that code perceived pain intensity when nociceptive input varies and/or receive direct nociceptive input. Pain inhibition by reward appears to involve brain regions not typically involved in nociceptive intensity coding but likely mediate changes in the significance and/or value of pain. © The Author (2017). Published by Oxford University Press.

Broca Pars Triangularis Constitutes a "Hub" of the Language-Control Network during Simultaneous Language Translation.

PubMed

Elmer, Stefan

2016-01-01

Until now, several branches of research have fundamentally contributed to a better understanding of the ramifications of bilingualism, multilingualism, and language expertise on psycholinguistic-, cognitive-, and neural implications. In this context, it is noteworthy to mention that from a cognitive perspective, there is a strong convergence of data pointing to an influence of multilingual speech competence on a variety of cognitive functions, including attention, short-term- and working memory, set shifting, switching, and inhibition. In addition, complementary neuroimaging findings have highlighted a specific set of cortical and subcortical brain regions which fundamentally contribute to administrate cognitive control in the multilingual brain, namely Broca's area, the middle-anterior cingulate cortex, the inferior parietal lobe, and the basal ganglia. However, a disadvantage of focusing on group analyses is that this procedure only enables an approximation of the neural networks shared within a population while at the same time smoothing inter-individual differences. In order to address both commonalities (i.e., within group analyses) and inter-individual variability (i.e., single-subject analyses) in language control mechanisms, here I measured five professional simultaneous interpreters while the participants overtly translated or repeated sentences with a simple subject-verb-object structure. Results demonstrated that pars triangularis was commonly activated across participants during backward translation (i.e., from L2 to L1), whereas the other brain regions of the "control network" showed a strong inter-individual variability during both backward and forward (i.e., from L1 to L2) translation. Thus, I propose that pars triangularis plays a crucial role within the language-control network and behaves as a fundamental processing entity supporting simultaneous language translation.

Real-time fMRI: a tool for local brain regulation.

PubMed

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.

Multisystem involvement of alveolar echinococcosis in a child.

PubMed

Kantarci, Mecit; Bayraktutan, Ummugulsum; Pirimoglu, Berhan; Ogul, Hayri; Oral, Akgun; Eren, Suat; Gundogdu, Betul

2014-11-13

Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a slowly progressing, life-threatening tumor-like growth in the liver. It may spread to other organs by regional extension or hematogenous or lymphatic metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the liver and simultaneous lung and brain metastasis with a literature review.

Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy

PubMed Central

Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.

2015-01-01

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327

Lateralized sex differences in stress-induced dopamine release in the rat.

PubMed

Sullivan, Ron M; Dufresne, Marc M; Waldron, Jay

2009-02-18

This study examined the possibility that hemispheric differences in stress-induced brain activation vary as a function of sex. Using in-vivo voltammetry, increases in extracellular dopamine release in response to predator odour and tail pinch stress were recorded bilaterally and simultaneously in either the infralimbic cortex or basolateral amygdala. In both stress-sensitive brain regions, significant sex x hemisphere interactions were observed, with males and females showing greater dopamine activation in right-brain and left-brain structures, respectively. Cortical asymmetries in dopamine release also showed sex-specific correlations with stress-induced neuroendocrine activation. Given the intriguing human parallels, we suggest that differential cerebral lateralization may be highly relevant to the disproportionately high incidence of stress-related disorders such as depression and anxiety seen in women.

Multi-neuron intracellular recording in vivo via interacting autopatching robots

PubMed Central

Holst, Gregory L; Singer, Annabelle C; Han, Xue; Brown, Emery N

2018-01-01

The activities of groups of neurons in a circuit or brain region are important for neuronal computations that contribute to behaviors and disease states. Traditional extracellular recordings have been powerful and scalable, but much less is known about the intracellular processes that lead to spiking activity. We present a robotic system, the multipatcher, capable of automatically obtaining blind whole-cell patch clamp recordings from multiple neurons simultaneously. The multipatcher significantly extends automated patch clamping, or 'autopatching’, to guide four interacting electrodes in a coordinated fashion, avoiding mechanical coupling in the brain. We demonstrate its performance in the cortex of anesthetized and awake mice. A multipatcher with four electrodes took an average of 10 min to obtain dual or triple recordings in 29% of trials in anesthetized mice, and in 18% of the trials in awake mice, thus illustrating practical yield and throughput to obtain multiple, simultaneous whole-cell recordings in vivo. PMID:29297466

Brain activity during bilateral rapid alternate finger tapping measured with magnetoencephalography

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu; Kodabashi, Atsushi; Fujimoto, Toshiro

2009-04-01

Using magnetoencephalography (MEG), brain regions involved in an alternate bimanual tapping task by index fingers triggered with spontaneous timing were investigated. The tapping mode in which both index fingers moved simultaneously was interlaced during the task. The groups of the alternate tapping (AL mode) and the simultaneous tapping (SI mode) were extracted from the successive alternating taps with a histogram of intervals between the right and left index fingers. MEG signals in each mode were averaged separately before and after the tapping initiation of the dominant index finger. The activities of the contralateral sensorimotor cortex before and after the tapping initiation in the AL mode were larger than that in the SI mode. The result indicates that the activity of the contralateral sensorimotor cortex depends on the degree of achievement in the difficult motor task such as the voluntary alternate tapping movements.

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice

PubMed Central

Pani, Amar K.; Jiao, Yun; Sample, Kenneth J.; Smeyne, Richard J.

2014-01-01

Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models. PMID:24642754

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

PubMed

Critchley, Hugo D; Rotshtein, Pia; Nagai, Yoko; O'Doherty, John; Mathias, Christopher J; Dolan, Raymond J

2005-02-01

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Simultaneous real-time monitoring of multiple cortical systems.

PubMed

Gupta, Disha; Jeremy Hill, N; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L; Schalk, Gerwin

2014-10-01

Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main Results: Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic.

Simultaneous Real-Time Monitoring of Multiple Cortical Systems

PubMed Central

Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

2014-01-01

Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic. PMID:25080161

Fast functional imaging of multiple brain regions in intact zebrafish larvae using selective plane illumination microscopy.

PubMed

Panier, Thomas; Romano, Sebastián A; Olive, Raphaël; Pietri, Thomas; Sumbre, Germán; Candelier, Raphaël; Debrégeas, Georges

2013-01-01

The optical transparency and the small dimensions of zebrafish at the larval stage make it a vertebrate model of choice for brain-wide in-vivo functional imaging. However, current point-scanning imaging techniques, such as two-photon or confocal microscopy, impose a strong limit on acquisition speed which in turn sets the number of neurons that can be simultaneously recorded. At 5 Hz, this number is of the order of one thousand, i.e., approximately 1-2% of the brain. Here we demonstrate that this limitation can be greatly overcome by using Selective-plane Illumination Microscopy (SPIM). Zebrafish larvae expressing the genetically encoded calcium indicator GCaMP3 were illuminated with a scanned laser sheet and imaged with a camera whose optical axis was oriented orthogonally to the illumination plane. This optical sectioning approach was shown to permit functional imaging of a very large fraction of the brain volume of 5-9-day-old larvae with single- or near single-cell resolution. The spontaneous activity of up to 5,000 neurons was recorded at 20 Hz for 20-60 min. By rapidly scanning the specimen in the axial direction, the activity of 25,000 individual neurons from 5 different z-planes (approximately 30% of the entire brain) could be simultaneously monitored at 4 Hz. Compared to point-scanning techniques, this imaging strategy thus yields a ≃20-fold increase in data throughput (number of recorded neurons times acquisition rate) without compromising the signal-to-noise ratio (SNR). The extended field of view offered by the SPIM method allowed us to directly identify large scale ensembles of neurons, spanning several brain regions, that displayed correlated activity and were thus likely to participate in common neural processes. The benefits and limitations of SPIM for functional imaging in zebrafish as well as future developments are briefly discussed.

The development of brain network architecture.

PubMed

Wierenga, Lara M; van den Heuvel, Martijn P; van Dijk, Sarai; Rijks, Yvonne; de Reus, Marcel A; Durston, Sarah

2016-02-01

Brain connectivity shows protracted development throughout childhood and adolescence, and, as such, the topology of brain networks changes during this period. The complexity of these changes with development is reflected by regional differences in maturation. This study explored age-related changes in network topology and regional developmental patterns during childhood and adolescence. We acquired two sets of Diffusion Weighted Imaging-scans and anatomical T1-weighted scans. The first dataset included 85 typically developing individuals (53 males; 32 females), aged between 7 and 23 years and was acquired on a Philips Achieva 1.5 Tesla scanner. A second dataset (N = 38) was acquired on a different (but identical) 1.5 T scanner and was used for independent replication of our results. We reconstructed whole brain networks using tractography. We operationalized fiber tract development as changes in mean diffusivity and radial diffusivity with age. Most fibers showed maturational changes in mean and radial diffusivity values throughout childhood and adolescence, likely reflecting increasing white matter integrity. The largest age-related changes were observed in association fibers within and between the frontal and parietal lobes. Furthermore, there was a simultaneous age-related decrease in average path length (P < 0.0001), increase in node strength (P < 0.0001) as well as network clustering (P = 0.001), which may reflect fine-tuning of topological organization. These results suggest a sequential maturational model where connections between unimodal regions strengthen in childhood, followed by connections from these unimodal regions to association regions, while adolescence is characterized by the strengthening of connections between association regions within the frontal and parietal cortex. Hum Brain Mapp 37:717-729, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain.

PubMed

Alves, Sandro; Bode, Julia; Bemelmans, Alexis-Pierre; von Kalle, Christof; Cartier, Nathalie; Tews, Björn

2016-06-20

Recombinant adeno-associated viral (AAV) vectors have advanced to the vanguard of gene therapy. Numerous naturally occurring serotypes have been used to target cells in various tissues. There is a strong need for fast and dynamic methods which efficiently unravel viral tropism in whole organs. Ultramicroscopy (UM) is a novel fluorescence microscopy technique that images optically cleared undissected specimens, achieving good resolutions at high penetration depths while being non-destructive. UM was applied to obtain high-resolution 3D analysis of AAV transduction in adult mouse brains, especially in the hippocampus, a region of interest for Alzheimer's disease therapy. We separately or simultaneously compared transduction efficacies for commonly used serotypes (AAV9 and AAVrh10) using fluorescent reporter expression. We provide a detailed comparative and quantitative analysis of the transduction profiles. UM allowed a rapid analysis of marker fluorescence expression in neurons with intact projections deep inside the brain, in defined anatomical structures. Major hippocampal neuronal transduction was observed with both vectors, with slightly better efficacy for AAV9 in UM. Glial response and synaptic marker expression did not change post transduction.We propose UM as a novel valuable complementary tool to efficiently and simultaneously unravel tropism of different viruses in a single non-dissected adult rodent brain.

fMRI reveals reciprocal inhibition between social and physical cognitive domains.

PubMed

Jack, Anthony I; Dawson, Abigail J; Begany, Katelyn L; Leckie, Regina L; Barry, Kevin P; Ciccia, Angela H; Snyder, Abraham Z

2013-02-01

Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which may be directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results indicate the reciprocal inhibition is not attributable to constraints inherent in the tasks, but is neural in origin. Hence, there is a physiological constraint on our ability to simultaneously engage two distinct cognitive modes. Further work is needed to more precisely characterize these opposing cognitive domains. Copyright © 2012 Elsevier Inc. All rights reserved.

Temporal Sequence of Ictal discharges Propagation in the Corticolimbic Basal Ganglia System during Amygdala Kindled Seizures in Freely Moving Rats

PubMed Central

Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu

2007-01-01

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434

Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

PubMed Central

2015-01-01

In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

Generate the scale-free brain music from BOLD signals

PubMed Central

Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

2018-01-01

Abstract Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen–Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon–Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. PMID:29480872

Generate the scale-free brain music from BOLD signals.

PubMed

Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

2018-01-01

Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen-Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon-Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS, fMRI, EEG Study.

PubMed

Anwar, A R; Muthalib, M; Perrey, S; Galka, A; Granert, O; Wolff, S; Heute, U; Deuschl, G; Raethjen, J; Muthuraman, Muthuraman

2016-09-01

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography-EEG) and hemodynamic (functional near infrared spectroscopy-fNIRS; and functional magnetic resonance imaging-fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O2Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O2Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.

Simultaneously uncovering the patterns of brain regions involved in different story reading subprocesses.

PubMed

Wehbe, Leila; Murphy, Brian; Talukdar, Partha; Fyshe, Alona; Ramdas, Aaditya; Mitchell, Tom

2014-01-01

Story understanding involves many perceptual and cognitive subprocesses, from perceiving individual words, to parsing sentences, to understanding the relationships among the story characters. We present an integrated computational model of reading that incorporates these and additional subprocesses, simultaneously discovering their fMRI signatures. Our model predicts the fMRI activity associated with reading arbitrary text passages, well enough to distinguish which of two story segments is being read with 74% accuracy. This approach is the first to simultaneously track diverse reading subprocesses during complex story processing and predict the detailed neural representation of diverse story features, ranging from visual word properties to the mention of different story characters and different actions they perform. We construct brain representation maps that replicate many results from a wide range of classical studies that focus each on one aspect of language processing and offer new insights on which type of information is processed by different areas involved in language processing. Additionally, this approach is promising for studying individual differences: it can be used to create single subject maps that may potentially be used to measure reading comprehension and diagnose reading disorders.

Bayesian reconstruction and use of anatomical a priori information for emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowsher, J.E.; Johnson, V.E.; Turkington, T.G.

1996-10-01

A Bayesian method is presented for simultaneously segmenting and reconstructing emission computed tomography (ECT) images and for incorporating high-resolution, anatomical information into those reconstructions. The anatomical information is often available from other imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI). The Bayesian procedure models the ECT radiopharmaceutical distribution as consisting of regions, such that radiopharmaceutical activity is similar throughout each region. It estimates the number of regions, the mean activity of each region, and the region classification and mean activity of each voxel. Anatomical information is incorporated by assigning higher prior probabilities to ECT segmentations inmore » which each ECT region stays within a single anatomical region. This approach is effective because anatomical tissue type often strongly influences radiopharmaceutical uptake. The Bayesian procedure is evaluated using physically acquired single-photon emission computed tomography (SPECT) projection data and MRI for the three-dimensional (3-D) Hoffman brain phantom. A clinically realistic count level is used. A cold lesion within the brain phantom is created during the SPECT scan but not during the MRI to demonstrate that the estimation procedure can detect ECT structure that is not present anatomically.« less

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

PubMed Central

Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

2015-01-01

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. PMID:25653107

Targeted, noninvasive blockade of cortical neuronal activity

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

2015-11-01

Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies.

[Post mortem temperature equilibration of the structures of the head. I. Thermometric techniques and principal investigations (author's transl)].

PubMed

Brinkmann, B; May, D; Riemann, U

1976-06-30

Special thin and flexible thermometric probes showing a diameter of 1 mm and a sharp end were used for post mortem (p.m.) thermometric studies in several tissues. Brain temperatures were measured by inserting a double probe through the superior orbital fissura thus allowing to record the central and the peripheral brain regions separately. Another probe was inserted into the galea and a fourth into the liver. Temperature changes were recorded simultaneously. Many variables of the human head were measured. Sixteen corpses were investigated. The results were as follows: 1. Of all temperature curves registered those of the central brain regions showed the smallest variance. 2. The p.m. temperature curve of the brain shows a sigmoid shape with a rather short "plateau" in the beginning. 3. In the early p.m. phase there is an increasing difference of temperatures between central and peripheral brain regions amounting to 2-4, 6 degrees C in the time period between 78th and 128th minute. 4. The insertion of the thin probes does not cause visible damages. Thus it should be considered for use in forensic practice. 5. Some artificial "head models" were constructed and temperature decrease recorded after warming. The curves showed the same type of sigmoid shape as those obtained from the corpses. 6. Of the possible variables measured that could influence the temperature decrease only the density of the hair seems to be of interest.

Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings.

PubMed

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.

Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

PubMed

Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

2016-08-01

SEE MATTAR ET AL DOI101093/AWW151 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

On the lorentzian versus Gaussian character of time-domain spin-echo signals from the brain as sampled by means of gradient-echoes: Implications for quantitative transverse relaxation studies.

PubMed

Mulkern, Robert V; Balasubramanian, Mukund; Mitsouras, Dimitrios

2014-07-30

To determine whether Lorentzian or Gaussian intra-voxel frequency distributions are better suited for modeling data acquired with gradient-echo sampling of single spin-echoes for the simultaneous characterization of irreversible and reversible relaxation rates. Clinical studies (e.g., of brain iron deposition) using such acquisition schemes have typically assumed Lorentzian distributions. Theoretical expressions of the time-domain spin-echo signal for intra-voxel Lorentzian and Gaussian distributions were used to fit data from a human brain scanned at both 1.5 Tesla (T) and 3T, resulting in maps of irreversible and reversible relaxation rates for each model. The relative merits of the Lorentzian versus Gaussian model were compared by means of quality of fit considerations. Lorentzian fits were equivalent to Gaussian fits primarily in regions of the brain where irreversible relaxation dominated. In the multiple brain regions where reversible relaxation effects become prominent, however, Gaussian fits were clearly superior. The widespread assumption that a Lorentzian distribution is suitable for quantitative transverse relaxation studies of the brain should be reconsidered, particularly at 3T and higher field strengths as reversible relaxation effects become more prominent. Gaussian distributions offer alternate fits of experimental data that should prove quite useful in general. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Dissociating verbal and nonverbal audiovisual object processing.

PubMed

Hocking, Julia; Price, Cathy J

2009-02-01

This fMRI study investigates how audiovisual integration differs for verbal stimuli that can be matched at a phonological level and nonverbal stimuli that can be matched at a semantic level. Subjects were presented simultaneously with one visual and one auditory stimulus and were instructed to decide whether these stimuli referred to the same object or not. Verbal stimuli were simultaneously presented spoken and written object names, and nonverbal stimuli were photographs of objects simultaneously presented with naturally occurring object sounds. Stimulus differences were controlled by including two further conditions that paired photographs of objects with spoken words and object sounds with written words. Verbal matching, relative to all other conditions, increased activation in a region of the left superior temporal sulcus that has previously been associated with phonological processing. Nonverbal matching, relative to all other conditions, increased activation in a right fusiform region that has previously been associated with structural and conceptual object processing. Thus, we demonstrate how brain activation for audiovisual integration depends on the verbal content of the stimuli, even when stimulus and task processing differences are controlled.

Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions

PubMed Central

Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

2018-01-01

Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. PMID:29467691

Tracking the Spatiotemporal Neural Dynamics of Real-world Object Size and Animacy in the Human Brain.

PubMed

Khaligh-Razavi, Seyed-Mahdi; Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2018-06-07

Animacy and real-world size are properties that describe any object and thus bring basic order into our perception of the visual world. Here, we investigated how the human brain processes real-world size and animacy. For this, we applied representational similarity to fMRI and MEG data to yield a view of brain activity with high spatial and temporal resolutions, respectively. Analysis of fMRI data revealed that a distributed and partly overlapping set of cortical regions extending from occipital to ventral and medial temporal cortex represented animacy and real-world size. Within this set, parahippocampal cortex stood out as the region representing animacy and size stronger than most other regions. Further analysis of the detailed representational format revealed differences among regions involved in processing animacy. Analysis of MEG data revealed overlapping temporal dynamics of animacy and real-world size processing starting at around 150 msec and provided the first neuromagnetic signature of real-world object size processing. Finally, to investigate the neural dynamics of size and animacy processing simultaneously in space and time, we combined MEG and fMRI with a novel extension of MEG-fMRI fusion by representational similarity. This analysis revealed partly overlapping and distributed spatiotemporal dynamics, with parahippocampal cortex singled out as a region that represented size and animacy persistently when other regions did not. Furthermore, the analysis highlighted the role of early visual cortex in representing real-world size. A control analysis revealed that the neural dynamics of processing animacy and size were distinct from the neural dynamics of processing low-level visual features. Together, our results provide a detailed spatiotemporal view of animacy and size processing in the human brain.

Whole Brain Networks for Treatment for Epilepsy

DTIC Science & Technology

2012-07-01

target. For the numerical approach, we applied both a simultaneous over- relaxation method (e.g. Gauss - Seidel ) and a biconjugate gradient...with b=1000sec/mm 2 and 7 b=0 acquisitions) was acquired on a Siemens TIM Trio (Siemens Medical Solutions, Erlangen) followed by iterative motion...partly from the difficulty with which the Monte Carlo approach is able to determine track densities at regions distal to the seed. Much iteration is

Perspectives on How Human Simultaneous Multi-Modal Imaging Adds Directionality to Spread Models of Alzheimer’s Disease

PubMed Central

Neitzel, Julia; Nuttall, Rachel; Sorg, Christian

2018-01-01

Previous animal research suggests that the spread of pathological agents in Alzheimer’s disease (AD) follows the direction of signaling pathways. Specifically, tau pathology has been suggested to propagate in an infection-like mode along axons, from transentorhinal cortices to medial temporal lobe cortices and consequently to other cortical regions, while amyloid-beta (Aβ) pathology seems to spread in an activity-dependent manner among and from isocortical regions into limbic and then subcortical regions. These directed connectivity-based spread models, however, have not been tested directly in AD patients due to the lack of an in vivo method to identify directed connectivity in humans. Recently, a new method—metabolic connectivity mapping (MCM)—has been developed and validated in healthy participants that uses simultaneous FDG-PET and resting-state fMRI data acquisition to identify directed intrinsic effective connectivity (EC). To this end, postsynaptic energy consumption (FDG-PET) is used to identify regions with afferent input from other functionally connected brain regions (resting-state fMRI). Here, we discuss how this multi-modal imaging approach allows quantitative, whole-brain mapping of signaling direction in AD patients, thereby pointing out some of the advantages it offers compared to other EC methods (i.e., Granger causality, dynamic causal modeling, Bayesian networks). Most importantly, MCM provides the basis on which models of pathology spread, derived from animal studies, can be tested in AD patients. In particular, future work should investigate whether tau and Aβ in humans propagate along the trajectories of directed connectivity in order to advance our understanding of the neuropathological mechanisms causing disease progression. PMID:29434570

Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration.

PubMed

Yang, Zhen-Zhen; Zhang, Yan-Qing; Wang, Zhan-Zhang; Wu, Kai; Lou, Jin-Ning; Qi, Xian-Rong

2013-08-16

Alzheimer's disease (AD) is a common progressive neurodegenerative disorder associated with cholinergic neurons degeneration. The blood-brain barrier (BBB) not only provides protection for the brain but also hinders the treatment and diagnosis of this neurological disease, because the drugs must cross BBB to reach the lesions. The present work was aimed at formulating rivastigmine liposomes (Lp) and cell-penetrating peptide (CPP) modified liposomes (CPP-Lp) to improve rivastigmine distribution in brain and proceed to enhance pharmacodynamics by intranasal (IN) administration and minimize side effects. The results revealed that Lp especially the CPP-Lp can enhance the permeability across the BBB by murine brain microvascular endothelial cells model in vitro. IN administration of rivastigmine solution and rivastigmine liposomes demonstrated the capacity to improve rivastigmine distribution and adequate retention in CNS regions especially in hippocampus and cortex, which were the regions most affected by AD, than that of IV administration. Importantly, the lagging but intense inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were relative to the extended release, absorption and retention. In addition, there was very mild nasal toxicity of liposomal formulations. The data suggest that rivastigmine liposomes especially CPP-Lp improve the brain delivery and enhance pharmacodynamics which respect to BBB penetration and nasal olfactory pathway into brain after IN administration, and simultaneously decrease the hepatic first pass metabolism and gastrointestinal adverse effects. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of multiple quaternary ammonium compounds in the brain using tandem capillary column separation and high resolution mass spectrometric detection.

PubMed

Falasca, Sara; Petruzziello, Filomena; Kretz, Robert; Rainer, Gregor; Zhang, Xiaozhe

2012-06-08

Endogenous quaternary ammonium compounds are involved in various physiological processes in the central nervous system. In the present study, eleven quaternary ammonium compounds, including acetylcholine, choline, carnitine, acetylcarnitine and seven other acylcarnitines of low polarity, were analyzed from brain extracts using a two dimension capillary liquid chromatography-Fourier transform mass spectrometry method. To deal with their large difference in hydrophobicities, tandem coupling between reversed phase and hydrophilic interaction chromatography columns was used to separate all the targeted quaternary ammonium compounds. Using high accuracy mass spectrometry in selected ion monitoring mode, all the compounds could be detected from each brain sample with high selectivity. The developed method was applied for the relative quantification of these quaternary ammonium compounds in three different brain regions of tree shrews: prefrontal cortex, striatum, and hippocampus. The comparative analysis showed that quaternary ammonium compounds were differentially distributed across the three brain areas. The analytical method proved to be highly sensitive and reliable for simultaneous determination of all the targeted analytes from brain samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Wide field-of-view, multi-region two-photon imaging of neuronal activity in the mammalian brain

PubMed Central

Stirman, Jeffrey N.; Smith, Ikuko T.; Kudenov, Michael W.; Smith, Spencer L.

2016-01-01

Two-photon calcium imaging provides an optical readout of neuronal activity in populations of neurons with subcellular resolution. However, conventional two-photon imaging systems are limited in their field of view to ~1 mm2, precluding the visualization of multiple cortical areas simultaneously. Here, we demonstrate a two-photon microscope with an expanded field of view (>9.5 mm2) for rapidly reconfigurable simultaneous scanning of widely separated populations of neurons. We custom designed and assembled an optimized scan engine, objective, and two independently positionable, temporally multiplexed excitation pathways. We used this new microscope to measure activity correlations between two cortical visual areas in mice during visual processing. PMID:27347754

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Regional and stage-specific effects of prospectively purified vascular cells on the adult V-SVZ neural stem cell lineage.

PubMed

Crouch, Elizabeth E; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

2015-03-18

Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contribution of pericytes to the neural stem cell niche has not been defined. Here, we describe a rapid FACS purification strategy to simultaneously isolate primary endothelial cells and pericytes from brain microregions of nontransgenic mice using CD31 and CD13 as surface markers. We compared the effect of purified vascular cells from a neurogenic (V-SVZ) and non-neurogenic brain region (cortex) on the V-SVZ stem cell lineage in vitro. Endothelial and pericyte diffusible signals from both regions differentially promote the proliferation and neuronal differentiation of qNSCs, aNSCs, and TACs. Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states. Copyright © 2015 the authors 0270-6474/15/354528-12$15.00/0.

A Gaussian mixture model based adaptive classifier for fNIRS brain-computer interfaces and its testing via simulation

NASA Astrophysics Data System (ADS)

Li, Zheng; Jiang, Yi-han; Duan, Lian; Zhu, Chao-zhe

2017-08-01

Objective. Functional near infra-red spectroscopy (fNIRS) is a promising brain imaging technology for brain-computer interfaces (BCI). Future clinical uses of fNIRS will likely require operation over long time spans, during which neural activation patterns may change. However, current decoders for fNIRS signals are not designed to handle changing activation patterns. The objective of this study is to test via simulations a new adaptive decoder for fNIRS signals, the Gaussian mixture model adaptive classifier (GMMAC). Approach. GMMAC can simultaneously classify and track activation pattern changes without the need for ground-truth labels. This adaptive classifier uses computationally efficient variational Bayesian inference to label new data points and update mixture model parameters, using the previous model parameters as priors. We test GMMAC in simulations in which neural activation patterns change over time and compare to static decoders and unsupervised adaptive linear discriminant analysis classifiers. Main results. Our simulation experiments show GMMAC can accurately decode under time-varying activation patterns: shifts of activation region, expansions of activation region, and combined contractions and shifts of activation region. Furthermore, the experiments show the proposed method can track the changing shape of the activation region. Compared to prior work, GMMAC performed significantly better than the other unsupervised adaptive classifiers on a difficult activation pattern change simulation: 99% versus  <54% in two-choice classification accuracy. Significance. We believe GMMAC will be useful for clinical fNIRS-based brain-computer interfaces, including neurofeedback training systems, where operation over long time spans is required.

HIV infection across aging: Synergistic effects on intrinsic functional connectivity of the brain.

PubMed

Egbert, Anna R; Biswal, Bharat; Karunakaran, Keerthana; Pluta, Agnieszka; Wolak, Tomasz; Rao, Stephen; Bornstein, Robert; Szymańska, Bogna; Horban, Andrzej; Firląg-Burkacka, Ewa; Sobańska, Marta; Gawron, Natalia; Bieńkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Ścińska-Bieńkowska, Anna; Łojek, Emilia

2018-06-12

The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV-) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20-55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients. Copyright © 2017. Published by Elsevier Inc.

Multiple foci of spatial attention in multimodal working memory.

PubMed

Katus, Tobias; Eimer, Martin

2016-11-15

The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

Hybrid ultrasound and dual-wavelength optoacoustic biomicroscopy for functional neuroimaging

NASA Astrophysics Data System (ADS)

Rebling, Johannes; Estrada, Hector; Zwack, Michael; Sela, Gali; Gottschalk, Sven; Razansky, Daniel

2017-03-01

Many neurological disorders are linked to abnormal activation or pathological alterations of the vasculature in the affected brain region. Obtaining simultaneous morphological and physiological information of neurovasculature is very challenging due to the acoustic distortions and intense light scattering by the skull and brain. In addition, the size of cerebral vasculature in murine brains spans an extended range from just a few microns up to about a millimeter, all to be recorded in 3D and over an area of several dozens of mm2. Numerous imaging techniques exist that excel at characterizing certain aspects of this complex network but are only capable of providing information on a limited spatiotemporal scale. We present a hybrid ultrasound and dual-wavelength optoacoustic microscope, capable of rapid imaging of murine neurovasculature in-vivo, with high spatial resolution down to 12 μm over a large field of view exceeding 50mm2. The dual wavelength imaging capability allows for the visualization of functional blood parameters through an intact skull while pulse-echo ultrasound biomicroscopy images are captured simultaneously by the same scan head. The flexible hybrid design in combination with fast high-resolution imaging in 3D holds promise for generating better insights into the architecture and function of the neurovascular system.

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

PubMed

Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

2016-03-01

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effect of MRI Acoustic Noise on Cerebral FDG Uptake in Simultaneous MR-PET Imaging

PubMed Central

Abolmaali, Nasreddin; Arabasz, Grae; Guimaraes, Alexander R.; Catana, Ciprian

2013-01-01

Integrated scanners capable of simultaneous PET and MRI data acquisition are now available for human use. Although the scanners’ manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the two modalities, the potential physiological inference has not been evaluated. In this work, we have studied the influence of the acoustic noise produced by the MR gradients on brain FDG uptake in the Siemens MR-BrainPET prototype. While particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. Methods The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, ten healthy volunteers underwent two simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a “quiet” (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a “noisy” (test) case in which MR sequences were run for the entire time. Cortical and subcortical regions of interest (ROIs) were derived from the high-resolution morphological MR data using FreeSurfer. The changes in FDG uptake in the FreeSurfer-derived ROIs between the two conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Results Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The ROI-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13±4.73%) and static (4.18±2.87%) images. SPM8 analysis showed no statistically significant clusters in any images when a p<0.05 (corrected) was used; however, a p<0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left: 8.37±1.55%, right: 8.20±1.17%), but only unilateral increase in the static image (left: 8.68±3.89%). Conclusion Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation related) changes in FDG uptake in this region, if the expected effects are of comparable amplitude. PMID:23462677

Connectivity in the human brain dissociates entropy and complexity of auditory inputs☆

PubMed Central

Nastase, Samuel A.; Iacovella, Vittorio; Davis, Ben; Hasson, Uri

2015-01-01

Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. PMID:25536493

Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

PubMed

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.

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

Simultaneous measurement of cerebral and muscle tissue parameters during cardiac arrest and cardiopulmonary resuscitation

NASA Astrophysics Data System (ADS)

Nosrati, Reyhaneh; Ramadeen, Andrew; Hu, Xudong; Woldemichael, Ermias; Kim, Siwook; Dorian, Paul; Toronov, Vladislav

2015-03-01

In this series of animal experiments on resuscitation after cardiac arrest we had a unique opportunity to measure hyperspectral near-infrared spectroscopy (hNIRS) parameters directly on the brain dura, or on the brain through the intact pig skull, and simultaneously the muscle hNIRS parameters. Simultaneously the arterial blood pressure and carotid and femoral blood flow were recorded in real time using invasive sensors. We used a novel hyperspectral signalprocessing algorithm to extract time-dependent concentrations of water, hemoglobin, and redox state of cytochrome c oxidase during cardiac arrest and resuscitation. In addition in order to assess the validity of the non-invasive brain measurements the obtained results from the open brain was compared to the results acquired through the skull. The comparison of hNIRS data acquired on brain surface and through the adult pig skull shows that in both cases the hemoglobin and the redox state cytochrome c oxidase changed in similar ways in similar situations and in agreement with blood pressure and flow changes. The comparison of simultaneously measured brain and muscle changes showed expected differences. Overall the results show feasibility of transcranial hNIRS measurements cerebral parameters including the redox state of cytochrome oxidase in human cardiac arrest patients.

Dual-echo ASL based assessment of motor networks: a feasibility study

NASA Astrophysics Data System (ADS)

Storti, Silvia Francesca; Boscolo Galazzo, Ilaria; Pizzini, Francesca B.; Menegaz, Gloria

2018-04-01

Objective. Dual-echo arterial spin labeling (DE-ASL) technique has been recently proposed for the simultaneous acquisition of ASL and blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) data. The assessment of this technique in detecting functional connectivity at rest or during motor and motor imagery tasks is still unexplored both per-se and in comparison with conventional methods. The purpose is to quantify the sensitivity of the DE-ASL sequence with respect to the conventional fMRI sequence (cvBOLD) in detecting brain activations, and to assess and compare the relevance of node features in decoding the network structure. Approach. Thirteen volunteers were scanned acquiring a pseudo-continuous DE-ASL sequence from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. The approach consists of two steps: (i) model-based analyses for assessing brain activations at individual and group levels, followed by statistical analysis for comparing the activation elicited by the three sequences under two conditions (motor and motor imagery), respectively; (ii) brain connectivity graph-theoretical analysis for assessing and comparing the network models properties. Main results. Our results suggest that cvBOLD and ccBOLD have comparable sensitivity in detecting the regions involved in the active task, whereas ASL offers a higher degree of co-localization with smaller activation volumes. The connectivity results and the comparative analysis of node features across sequences revealed that there are no strong changes between rest and tasks and that the differences between the sequences are limited to few connections. Significance. Considering the comparable sensitivity of the ccBOLD and cvBOLD sequences in detecting activated brain regions, the results demonstrate that DE-ASL can be successfully applied in functional studies allowing to obtain both ASL and BOLD information within a single sequence. Further, DE-ASL is a powerful technique for research and clinical applications allowing to perform quantitative comparisons as well as to characterize functional connectivity.

Micromachined lab-on-a-tube sensors for simultaneous brain temperature and cerebral blood flow measurements.

PubMed

Li, Chunyan; Wu, Pei-Ming; Hartings, Jed A; Wu, Zhizhen; Cheyuo, Cletus; Wang, Ping; LeDoux, David; Shutter, Lori A; Ramaswamy, Bharat Ram; Ahn, Chong H; Narayan, Raj K

2012-08-01

This work describes the development of a micromachined lab-on-a-tube device for simultaneous measurement of brain temperature and regional cerebral blood flow. The device consists of two micromachined gold resistance temperature detectors with a 4-wire configuration. One is used as a temperature sensor and the other as a flow sensor. The temperature sensor operates with AC excitation current of 500 μA and updates its outputs at a rate of 5 Hz. The flow sensor employs a periodic heating and cooling technique under constant-temperature mode and updates its outputs at a rate of 0.1 Hz. The temperature sensor is also used to compensate for temperature changes during the heating period of the flow sensor to improve the accuracy of flow measurements. To prevent thermal and electronic crosstalk between the sensors, the temperature sensor is located outside the "thermal influence" region of the flow sensor and the sensors are separated into two different layers with a thin-film Copper shield. We evaluated the sensors for accuracy, crosstalk and long-term drift in human blood-stained cerebrospinal fluid. These in vitro experiments showed that simultaneous temperature and flow measurements with a single lab-on-a-tube device are accurate and reliable over the course of 5 days. It has a resolution of 0.013 °C and 0.18 ml/100 g/min; and achieves an accuracy of 0.1 °C and 5 ml/100 g/min for temperature and flow sensors respectively. The prototype device and techniques developed here establish a foundation for a multi-sensor lab-on-a-tube, enabling versatile multimodality monitoring applications.

Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.

Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissuemore » samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.« less

Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain.

PubMed

Schou-Pedersen, Anne Marie V; Hansen, Stine N; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

2016-08-15

In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9±9.9 to 120±14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry. Copyright © 2016 Elsevier B.V. All rights reserved.

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS).

PubMed

Menze, Bjoern H; Jakab, Andras; Bauer, Stefan; Kalpathy-Cramer, Jayashree; Farahani, Keyvan; Kirby, Justin; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland; Lanczi, Levente; Gerstner, Elizabeth; Weber, Marc-André; Arbel, Tal; Avants, Brian B; Ayache, Nicholas; Buendia, Patricia; Collins, D Louis; Cordier, Nicolas; Corso, Jason J; Criminisi, Antonio; Das, Tilak; Delingette, Hervé; Demiralp, Çağatay; Durst, Christopher R; Dojat, Michel; Doyle, Senan; Festa, Joana; Forbes, Florence; Geremia, Ezequiel; Glocker, Ben; Golland, Polina; Guo, Xiaotao; Hamamci, Andac; Iftekharuddin, Khan M; Jena, Raj; John, Nigel M; Konukoglu, Ender; Lashkari, Danial; Mariz, José Antonió; Meier, Raphael; Pereira, Sérgio; Precup, Doina; Price, Stephen J; Raviv, Tammy Riklin; Reza, Syed M S; Ryan, Michael; Sarikaya, Duygu; Schwartz, Lawrence; Shin, Hoo-Chang; Shotton, Jamie; Silva, Carlos A; Sousa, Nuno; Subbanna, Nagesh K; Szekely, Gabor; Taylor, Thomas J; Thomas, Owen M; Tustison, Nicholas J; Unal, Gozde; Vasseur, Flor; Wintermark, Max; Ye, Dong Hye; Zhao, Liang; Zhao, Binsheng; Zikic, Darko; Prastawa, Marcel; Reyes, Mauricio; Van Leemput, Koen

2015-10-01

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

PubMed Central

Jakab, Andras; Bauer, Stefan; Kalpathy-Cramer, Jayashree; Farahani, Keyvan; Kirby, Justin; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland; Lanczi, Levente; Gerstner, Elizabeth; Weber, Marc-André; Arbel, Tal; Avants, Brian B.; Ayache, Nicholas; Buendia, Patricia; Collins, D. Louis; Cordier, Nicolas; Corso, Jason J.; Criminisi, Antonio; Das, Tilak; Delingette, Hervé; Demiralp, Çağatay; Durst, Christopher R.; Dojat, Michel; Doyle, Senan; Festa, Joana; Forbes, Florence; Geremia, Ezequiel; Glocker, Ben; Golland, Polina; Guo, Xiaotao; Hamamci, Andac; Iftekharuddin, Khan M.; Jena, Raj; John, Nigel M.; Konukoglu, Ender; Lashkari, Danial; Mariz, José António; Meier, Raphael; Pereira, Sérgio; Precup, Doina; Price, Stephen J.; Raviv, Tammy Riklin; Reza, Syed M. S.; Ryan, Michael; Sarikaya, Duygu; Schwartz, Lawrence; Shin, Hoo-Chang; Shotton, Jamie; Silva, Carlos A.; Sousa, Nuno; Subbanna, Nagesh K.; Szekely, Gabor; Taylor, Thomas J.; Thomas, Owen M.; Tustison, Nicholas J.; Unal, Gozde; Vasseur, Flor; Wintermark, Max; Ye, Dong Hye; Zhao, Liang; Zhao, Binsheng; Zikic, Darko; Prastawa, Marcel; Reyes, Mauricio; Van Leemput, Koen

2016-01-01

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients—manually annotated by up to four raters—and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%–85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource. PMID:25494501

The duality of temporal encoding – the intrinsic and extrinsic representation of time

PubMed Central

Golan, Ronen; Zakay, Dan

2015-01-01

While time is well acknowledged for having a fundamental part in our perception, questions on how it is represented are still matters of great debate. One of the main issues in question is whether time is represented intrinsically at the neural level, or is it represented within dedicated brain regions. We used an fMRI block design to test if we can impose covert encoding of temporal features of faces and natural scenes stimuli within category selective neural populations by exposing subjects to four types of temporal variance, ranging from 0% up to 50% variance. We found a gradual increase in neural activation associated with the gradual increase in temporal variance within category selective areas. A second level analysis showed the same pattern of activations within known brain regions associated with time representation, such as the Cerebellum, the Caudate, and the Thalamus. We concluded that temporal features are integral to perception and are simultaneously represented within category selective regions and globally within dedicated regions. Our second conclusion, drown from our covert procedure, is that time encoding, at its basic level, is an automated process that does not require attention allocated toward the temporal features nor does it require dedicated resources. PMID:26379604

Wavelength Dependence of Effective Pathlength Factor in Noninvasive Optical Measurements of Human Brain Functions

NASA Astrophysics Data System (ADS)

Sato, Hiroki; Kiguchi, Masashi; Maki, Atsushi

2006-04-01

In the noninvasive optical measurements of human brain functions, the dependence of pathlength factor in an activation area (effective pathlength factor: EPF) on wavelength was examined by simultaneously recording five wavelengths of 678, 692, 750, 782, and 830 nm, with three different source/detector distances of 20, 30, and 40 mm. We obtained an activation signal in the visual cortex using four wavelength pairs, where 830 nm was fixed as one wavelength. The dependence of EPF on the source/detector distance showed similar tendencies when the wavelengths of 692, 750, and 782 nm were considered. This suggests that it is feasible to use these wavelengths paired with an 830 nm wavelength to investigate the same region.

Audiovisual Temporal Processing and Synchrony Perception in the Rat.

PubMed

Schormans, Ashley L; Scott, Kaela E; Vo, Albert M Q; Tyker, Anna; Typlt, Marei; Stolzberg, Daniel; Allman, Brian L

2016-01-01

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer's ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats ( n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats ( n = 7) perceived the synchronous audiovisual stimuli to be "visual first" for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20-40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level.

Audiovisual Temporal Processing and Synchrony Perception in the Rat

PubMed Central

Schormans, Ashley L.; Scott, Kaela E.; Vo, Albert M. Q.; Tyker, Anna; Typlt, Marei; Stolzberg, Daniel; Allman, Brian L.

2017-01-01

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer’s ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats (n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats (n = 7) perceived the synchronous audiovisual stimuli to be “visual first” for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20–40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level. PMID:28119580

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Acute in vivo testing of a conformal polymer microelectrode array for multi-region hippocampal recordings

NASA Astrophysics Data System (ADS)

Xu, Huijing; Weltman Hirschberg, Ahuva; Scholten, Kee; Berger, Theodore William; Song, Dong; Meng, Ellis

2018-02-01

Objective. The success of a cortical prosthetic device relies upon its ability to attain resolvable spikes from many neurons in particular neural networks over long periods of time. Traditionally, lifetimes of neural recordings are greatly limited by the body’s immune response against the foreign implant which causes neuronal death and glial scarring. This immune reaction is posited to be exacerbated by micromotion between the implant, which is often rigid, and the surrounding, soft brain tissue, and attenuates the quality of recordings over time. Approach. In an attempt to minimize the foreign body response to a penetrating neural array that records from multiple brain regions, Parylene C, a flexible, biocompatible polymer was used as the substrate material for a functional, proof-of-concept neural array with a reduced elastic modulus. This probe array was designed and fabricated to have 64 electrodes positioned to match the anatomy of the rat hippocampus and allow for simultaneous recordings between two cell-body layers of interest. A dissolvable brace was used for deep-brain penetration of the flexible array. Main results. Arrays were electrochemically characterized at the benchtop, and a novel insertion technique that restricts acute insertion injury enabled accurate target placement of four, bare, flexible arrays to greater than 4 mm deep into the rat brain. Arrays were tested acutely and in vivo recordings taken intra-operatively reveal spikes in both targeted regions of the hippocampus with spike amplitudes and noise levels similar to those recorded with microwires. Histological staining of a sham array implanted for one month reveals limited astrocytic scarring and neuronal death around the implant. Significance. This work represents one of the first examples of a penetrating polymer probe array that records from individual neurons in structures that lie deep within the brain.

Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications

PubMed Central

Markovitz, Craig D.; Tang, Tien T.; Edge, David P.; Lim, Hubert H.

2012-01-01

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics. PMID:22754502

Optical barcoding of PLGA for multispectral analysis of nanoparticle fate in vivo.

PubMed

Medina, David X; Householder, Kyle T; Ceton, Ricki; Kovalik, Tina; Heffernan, John M; Shankar, Rohini V; Bowser, Robert P; Wechsler-Reya, Robert J; Sirianni, Rachael W

2017-05-10

Understanding of the mechanisms by which systemically administered nanoparticles achieve delivery across biological barriers remains incomplete, due in part to the challenge of tracking nanoparticle fate in the body. Here, we develop a new approach for "barcoding" nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) with bright, spectrally defined quantum dots (QDs) to enable direct, fluorescent detection of nanoparticle fate with subcellular resolution. We show that QD labeling does not affect major biophysical properties of nanoparticles or their interaction with cells and tissues. Live cell imaging enabled simultaneous visualization of the interaction of control and targeted nanoparticles with bEnd.3 cells in a flow chamber, providing direct evidence that surface modification of nanoparticles with the cell-penetrating peptide TAT increases their biophysical association with cell surfaces over very short time periods under convective current. We next developed this technique for quantitative biodistribution analysis in vivo. These studies demonstrate that nanoparticle surface modification with the cell penetrating peptide TAT facilitates brain-specific delivery that is restricted to brain vasculature. Although nanoparticle entry into the healthy brain parenchyma is minimal, with no evidence for movement of nanoparticles across the blood-brain barrier (BBB), we observed that nanoparticles are able to enter to the central nervous system (CNS) through regions of altered BBB permeability - for example, into circumventricular organs in the brain or leaky vasculature of late-stage intracranial tumors. In sum, these data demonstrate a new, multispectral approach for barcoding PLGA, which enables simultaneous, quantitative analysis of the fate of multiple nanoparticle formulations in vivo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Expert system for neurosurgical treatment planning

NASA Astrophysics Data System (ADS)

Cheng, Andrew Y. S.; Chung, Sally S. Y.; Kwok, John C. K.

1996-04-01

A specially designed expert system is in development for neurosurgical treatment planning. The knowledge base contains knowledge and experiences on neurosurgical treatment planning from neurosurgeon consultants, who also determine the risks of different regions in human brains. When completed, the system can simulate the decision making process of neurosurgeons to determine the safest probing path for operation. The Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan images for each patient are grabbed as the input. The system also allows neurosurgeons to include for any particular patient the additional information, such as how the tumor affects its neighboring functional regions, which is also important for calculating the safest probing path. It can then consider all the relevant information and find the most suitable probing path on the patient's brain. A 3D brain model is constructed for each set of the CT/MRI scan images and is displayed real-time together with the possible probing paths found. The precise risk value of each path is shown as a number between 0 and 1, together with its possible damages in text. Neurosurgeons can view more than one possible path simultaneously, and make the final decision on the selected path for operation.

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

PubMed

Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M

2018-05-07

A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.

Multisensory integration processing during olfactory-visual stimulation-An fMRI graph theoretical network analysis.

PubMed

Ripp, Isabelle; Zur Nieden, Anna-Nora; Blankenagel, Sonja; Franzmeier, Nicolai; Lundström, Johan N; Freiherr, Jessica

2018-05-07

In this study, we aimed to understand how whole-brain neural networks compute sensory information integration based on the olfactory and visual system. Task-related functional magnetic resonance imaging (fMRI) data was obtained during unimodal and bimodal sensory stimulation. Based on the identification of multisensory integration processing (MIP) specific hub-like network nodes analyzed with network-based statistics using region-of-interest based connectivity matrices, we conclude the following brain areas to be important for processing the presented bimodal sensory information: right precuneus connected contralaterally to the supramarginal gyrus for memory-related imagery and phonology retrieval, and the left middle occipital gyrus connected ipsilaterally to the inferior frontal gyrus via the inferior fronto-occipital fasciculus including functional aspects of working memory. Applied graph theory for quantification of the resulting complex network topologies indicates a significantly increased global efficiency and clustering coefficient in networks including aspects of MIP reflecting a simultaneous better integration and segregation. Graph theoretical analysis of positive and negative network correlations allowing for inferences about excitatory and inhibitory network architectures revealed-not significant, but very consistent-that MIP-specific neural networks are dominated by inhibitory relationships between brain regions involved in stimulus processing. © 2018 Wiley Periodicals, Inc.

Cy5.5 conjugated MnO nanoparticles for magnetic resonance/near-infrared fluorescence dual-modal imaging of brain gliomas.

PubMed

Chen, Ning; Shao, Chen; Li, Shuai; Wang, Zihao; Qu, Yanming; Gu, Wei; Yu, Chunjiang; Ye, Ling

2015-11-01

The fusion of molecular and anatomical modalities facilitates more reliable and accurate detection of tumors. Herein, we prepared the PEG-Cy5.5 conjugated MnO nanoparticles (MnO-PEG-Cy5.5 NPs) with magnetic resonance (MR) and near-infrared fluorescence (NIRF) imaging modalities. The applicability of MnO-PEG-Cy5.5 NPs as a dual-modal (MR/NIRF) imaging nanoprobe for the detection of brain gliomas was investigated. In vivo MR contrast enhancement of the MnO-PEG-Cy5.5 nanoprobe in the tumor region was demonstrated. Meanwhile, whole-body NIRF imaging of glioma bearing nude mouse exhibited distinct tumor localization upon injection of MnO-PEG-Cy5.5 NPs. Moreover, ex vivo CLSM imaging of the brain slice hosting glioma indicated the preferential accumulation of MnO-PEG-Cy5.5 NPs in the glioma region. Our results therefore demonstrated the potential of MnO-PEG-Cy5.5 NPs as a dual-modal (MR/NIRF) imaging nanoprobe in improving the diagnostic efficacy by simultaneously providing anatomical information from deep inside the body and more sensitive information at the cellular level. Copyright © 2015 Elsevier Inc. All rights reserved.

Continuous blood pressure recordings simultaneously with functional brain imaging: studies of the glymphatic system

NASA Astrophysics Data System (ADS)

Zienkiewicz, Aleksandra; Huotari, Niko; Raitamaa, Lauri; Raatikainen, Ville; Ferdinando, Hany; Vihriälä, Erkki; Korhonen, Vesa; Myllylä, Teemu; Kiviniemi, Vesa

2017-03-01

The lymph system is responsible for cleaning the tissues of metabolic waste products, soluble proteins and other harmful fluids etc. Lymph flow in the body is driven by body movements and muscle contractions. Moreover, it is indirectly dependent on the cardiovascular system, where the heart beat and blood pressure maintain force of pressure in lymphatic channels. Over the last few years, studies revealed that the brain contains the so-called glymphatic system, which is the counterpart of the systemic lymphatic system in the brain. Similarly, the flow in the glymphatic system is assumed to be mostly driven by physiological pulsations such as cardiovascular pulses. Thus, continuous measurement of blood pressure and heart function simultaneously with functional brain imaging is of great interest, particularly in studies of the glymphatic system. We present our MRI compatible optics based sensing system for continuous blood pressure measurement and show our current results on the effects of blood pressure variations on cerebral brain dynamics, with a focus on the glymphatic system. Blood pressure was measured simultaneously with near-infrared spectroscopy (NIRS) combined with an ultrafast functional brain imaging (fMRI) sequence magnetic resonance encephalography (MREG, 3D brain 10 Hz sampling rate).

Single cell gene expression profiling in Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Che, Shaoli; Counts, Scott E; Mufson, Elliott J

2006-07-01

Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

Cerebellum and Integration of Neural Networks in Dual-Task Processing

PubMed Central

Wu, Tao; Liu, Jun; Hallett, Mark; Zheng, Zheng; Chan, Piu

2014-01-01

Performing two tasks simultaneously (dual-task) is common in human daily life. The neural correlates of dual-task processing remain unclear. In the current study, we used a dual motor and counting task with functional MRI (fMRI) to determine whether there are any areas additionally activated for dual-task performance. Moreover, we investigated the functional connectivity of these added activated areas, as well as the training effect on brain activity and connectivity. We found that the right cerebellar vermis, left lobule V of the cerebellar anterior lobe and precuneus are additionally activated for this type of dual-tasking. These cerebellar regions had functional connectivity with extensive motor- and cognitive-related regions. Dual-task training induced less activation in several areas, but increased the functional connectivity between these cerebellar regions and numbers of motor- and cognitive-related areas. Our findings demonstrate that some regions within the cerebellum can be additionally activated with dual-task performance. Their role in dual motor and cognitive task processes is likely to integrate motor and cognitive networks, and may be involved in adjusting these networks to be more efficient in order to perform dual-tasking properly. The connectivity of the precuneus differs from the cerebellar regions. A possible role of the precuneus in dual-task may be monitoring the operation of active brain networks. PMID:23063842

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.

PubMed

McKenna, Dennis; Riba, Jordi

2018-01-01

New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain. Using complementary neurophysiological and neuroimaging techniques, we have identified brain areas involved in the cognitive effects induced by this complex botanical preparation. Initial SPECT data showed that ayahuasca modulated activity in higher order association areas of the brain. Increased blood perfusion was observed mainly in anterior brain regions encompassing the frontomedial and anterior cingulate cortices of the frontal lobes, and in the medial regions of the temporal lobes. On the other hand, applying spectral analysis and source location techniques to cortical electrical signals, we found changes in neuronal activity that predominated in more posterior sensory-selective areas of the brain. Now, using functional connectivity analysis of brain oscillations we have been able to reconcile these seemingly contradictory findings. By measuring transfer entropy, a metric based on information theory, we have shown that ayahuasca temporarily modifies the ordinary flow of information within the brain. We propose a model in which ayahuasca reduces top-down constraints and facilitates bottom-up information transfer. By simultaneously enhancing endogenous cortical excitability and reducing higher-order cognitive control, ayahuasca temporarily disrupts neural hierarchies allowing inner exploration and a new outlook on reality.

Cerebrovascular aspects of converting-enzyme inhibition II: Blood-brain barrier permeability and effect of intracerebroventricular administration of captopril.

PubMed

Jarden, J O; Barry, D I; Juhler, M; Graham, D I; Strandgaard, S; Paulson, O B

1984-12-01

The blood-brain barrier permeability to captopril, and the cerebrovascular effects of intracerebroventricular administration of captopril, were studied in normotensive Wistar rats. The blood-brain barrier permeability-surface area product (PS), determined by an integral-uptake method, was about 1 X 10(-5) cm3/g/s in all brain regions studied. This was three to four times lower than the simultaneously determined PS of Na+ and Cl-, both of which are known to have very low blood-brain barrier permeability. Cerebral blood flow, determined by the intra-arterial 133xenon injection method, was unaffected by intracerebroventricular administration of 100 micrograms captopril. Furthermore the lower limit of cerebral blood flow autoregulation during haemorrhagic hypotension was also unaffected, being in the mean arterial pressure range (50-69 mmHg) in both controls and captopril-treated rats. It was concluded that the blood-brain barrier permeability of captopril was negligible and that inhibition of the brain renin-angiotensin system has no effect on global cerebral blood flow. The cerebrovascular effects of intravenously administered captopril (a resetting to lower pressure of the limits and range of cerebral blood flow autoregulation) are probably exerted via converting enzyme on the luminal surface of cerebral vessels.

Chemical reactivation of resin-embedded pHuji adds red for simultaneous two-color imaging with EGFP

PubMed Central

Guo, Wenyan; Liu, Xiuli; Liu, Yurong; Gang, Yadong; He, Xiaobin; Jia, Yao; Yin, Fangfang; Li, Pei; Huang, Fei; Zhou, Hongfu; Wang, Xiaojun; Gong, Hui; Luo, Qingming; Xu, Fuqiang; Zeng, Shaoqun

2017-01-01

The pH-sensitive fluorescent proteins enabling chemical reactivation in resin are useful tools for fluorescence microimaging. EGFP or EYFP is good for such applications. For simultaneous two-color imaging, a suitable red fluorescent protein is an urgent need. Here a pH-sensitive red fluorescent protein, pHuji, is selected and verified to remain pH-sensitive in HM20 resin. We observe 183% fluorescence intensity of pHuji in resin-embeded mouse brain and 29.08-fold fluorescence intensity of reactivated pHuji compared to the quenched state. pHuji and EGFP can be quenched and chemically reactivated simultaneously in resin, thus enabling simultaneous two-color micro-optical sectioning tomography of resin-embedded mouse brain. This method may greatly facilitate the visualization of neuronal morphology and neural circuits to promote understanding of the structure and function of the brain. PMID:28717566

Chemical reactivation of resin-embedded pHuji adds red for simultaneous two-color imaging with EGFP.

PubMed

Guo, Wenyan; Liu, Xiuli; Liu, Yurong; Gang, Yadong; He, Xiaobin; Jia, Yao; Yin, Fangfang; Li, Pei; Huang, Fei; Zhou, Hongfu; Wang, Xiaojun; Gong, Hui; Luo, Qingming; Xu, Fuqiang; Zeng, Shaoqun

2017-07-01

The pH-sensitive fluorescent proteins enabling chemical reactivation in resin are useful tools for fluorescence microimaging. EGFP or EYFP is good for such applications. For simultaneous two-color imaging, a suitable red fluorescent protein is an urgent need. Here a pH-sensitive red fluorescent protein, pHuji, is selected and verified to remain pH-sensitive in HM20 resin. We observe 183% fluorescence intensity of pHuji in resin-embeded mouse brain and 29.08-fold fluorescence intensity of reactivated pHuji compared to the quenched state. pHuji and EGFP can be quenched and chemically reactivated simultaneously in resin, thus enabling simultaneous two-color micro-optical sectioning tomography of resin-embedded mouse brain. This method may greatly facilitate the visualization of neuronal morphology and neural circuits to promote understanding of the structure and function of the brain.

Generative adversarial networks for brain lesion detection

NASA Astrophysics Data System (ADS)

Alex, Varghese; Safwan, K. P. Mohammed; Chennamsetty, Sai Saketh; Krishnamurthi, Ganapathy

2017-02-01

Manual segmentation of brain lesions from Magnetic Resonance Images (MRI) is cumbersome and introduces errors due to inter-rater variability. This paper introduces a semi-supervised technique for detection of brain lesion from MRI using Generative Adversarial Networks (GANs). GANs comprises of a Generator network and a Discriminator network which are trained simultaneously with the objective of one bettering the other. The networks were trained using non lesion patches (n=13,000) from 4 different MR sequences. The network was trained on BraTS dataset and patches were extracted from regions excluding tumor region. The Generator network generates data by modeling the underlying probability distribution of the training data, (PData). The Discriminator learns the posterior probability P (Label Data) by classifying training data and generated data as "Real" or "Fake" respectively. The Generator upon learning the joint distribution, produces images/patches such that the performance of the Discriminator on them are random, i.e. P (Label Data = GeneratedData) = 0.5. During testing, the Discriminator assigns posterior probability values close to 0.5 for patches from non lesion regions, while patches centered on lesion arise from a different distribution (PLesion) and hence are assigned lower posterior probability value by the Discriminator. On the test set (n=14), the proposed technique achieves whole tumor dice score of 0.69, sensitivity of 91% and specificity of 59%. Additionally the generator network was capable of generating non lesion patches from various MR sequences.

Building the Ferretome

PubMed Central

Sukhinin, Dmitrii I.; Engel, Andreas K.; Manger, Paul; Hilgetag, Claus C.

2016-01-01

Databases of structural connections of the mammalian brain, such as CoCoMac (cocomac.g-node.org) or BAMS (https://bams1.org), are valuable resources for the analysis of brain connectivity and the modeling of brain dynamics in species such as the non-human primate or the rodent, and have also contributed to the computational modeling of the human brain. Another animal model that is widely used in electrophysiological or developmental studies is the ferret; however, no systematic compilation of brain connectivity is currently available for this species. Thus, we have started developing a database of anatomical connections and architectonic features of the ferret brain, the Ferret(connect)ome, www.Ferretome.org. The Ferretome database has adapted essential features of the CoCoMac methodology and legacy, such as the CoCoMac data model. This data model was simplified and extended in order to accommodate new data modalities that were not represented previously, such as the cytoarchitecture of brain areas. The Ferretome uses a semantic parcellation of brain regions as well as a logical brain map transformation algorithm (objective relational transformation, ORT). The ORT algorithm was also adopted for the transformation of architecture data. The database is being developed in MySQL and has been populated with literature reports on tract-tracing observations in the ferret brain using a custom-designed web interface that allows efficient and validated simultaneous input and proofreading by multiple curators. The database is equipped with a non-specialist web interface. This interface can be extended to produce connectivity matrices in several formats, including a graphical representation superimposed on established ferret brain maps. An important feature of the Ferretome database is the possibility to trace back entries in connectivity matrices to the original studies archived in the system. Currently, the Ferretome contains 50 reports on connections comprising 20 injection reports with more than 150 labeled source and target areas, the majority reflecting connectivity of subcortical nuclei and 15 descriptions of regional brain architecture. We hope that the Ferretome database will become a useful resource for neuroinformatics and neural modeling, and will support studies of the ferret brain as well as facilitate advances in comparative studies of mesoscopic brain connectivity. PMID:27242503

Building the Ferretome.

PubMed

Sukhinin, Dmitrii I; Engel, Andreas K; Manger, Paul; Hilgetag, Claus C

2016-01-01

Databases of structural connections of the mammalian brain, such as CoCoMac (cocomac.g-node.org) or BAMS (https://bams1.org), are valuable resources for the analysis of brain connectivity and the modeling of brain dynamics in species such as the non-human primate or the rodent, and have also contributed to the computational modeling of the human brain. Another animal model that is widely used in electrophysiological or developmental studies is the ferret; however, no systematic compilation of brain connectivity is currently available for this species. Thus, we have started developing a database of anatomical connections and architectonic features of the ferret brain, the Ferret(connect)ome, www.Ferretome.org. The Ferretome database has adapted essential features of the CoCoMac methodology and legacy, such as the CoCoMac data model. This data model was simplified and extended in order to accommodate new data modalities that were not represented previously, such as the cytoarchitecture of brain areas. The Ferretome uses a semantic parcellation of brain regions as well as a logical brain map transformation algorithm (objective relational transformation, ORT). The ORT algorithm was also adopted for the transformation of architecture data. The database is being developed in MySQL and has been populated with literature reports on tract-tracing observations in the ferret brain using a custom-designed web interface that allows efficient and validated simultaneous input and proofreading by multiple curators. The database is equipped with a non-specialist web interface. This interface can be extended to produce connectivity matrices in several formats, including a graphical representation superimposed on established ferret brain maps. An important feature of the Ferretome database is the possibility to trace back entries in connectivity matrices to the original studies archived in the system. Currently, the Ferretome contains 50 reports on connections comprising 20 injection reports with more than 150 labeled source and target areas, the majority reflecting connectivity of subcortical nuclei and 15 descriptions of regional brain architecture. We hope that the Ferretome database will become a useful resource for neuroinformatics and neural modeling, and will support studies of the ferret brain as well as facilitate advances in comparative studies of mesoscopic brain connectivity.

Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

PubMed

Combaz, Adrien; Van Hulle, Marc M

2015-01-01

We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

A silicon-based microelectrode array with a microdrive for monitoring brainstem regions of freely moving rats

NASA Astrophysics Data System (ADS)

Márton, G.; Baracskay, P.; Cseri, B.; Plósz, B.; Juhász, G.; Fekete, Z.; Pongrácz, A.

2016-04-01

Objective. Exploring neural activity behind synchronization and time locking in brain circuits is one of the most important tasks in neuroscience. Our goal was to design and characterize a microelectrode array (MEA) system specifically for obtaining in vivo extracellular recordings from three deep-brain areas of freely moving rats, simultaneously. The target areas, the deep mesencephalic reticular-, pedunculopontine tegmental- and pontine reticular nuclei are related to the regulation of sleep-wake cycles. Approach. The three targeted nuclei are collinear, therefore a single-shank MEA was designed in order to contact them. The silicon-based device was equipped with 3*4 recording sites, located according to the geometry of the brain regions. Furthermore, a microdrive was developed to allow fine actuation and post-implantation relocation of the probe. The probe was attached to a rigid printed circuit board, which was fastened to the microdrive. A flexible cable was designed in order to provide not only electronic connection between the probe and the amplifier system, but sufficient freedom for the movements of the probe as well. Main results. The microdrive was stable enough to allow precise electrode targeting into the tissue via a single track. The microelectrodes on the probe were suitable for recording neural activity from the three targeted brainstem areas. Significance. The system offers a robust solution to provide long-term interface between an array of precisely defined microelectrodes and deep-brain areas of a behaving rodent. The microdrive allowed us to fine-tune the probe location and easily scan through the regions of interest.

Connectivity in the human brain dissociates entropy and complexity of auditory inputs.

PubMed

Nastase, Samuel A; Iacovella, Vittorio; Davis, Ben; Hasson, Uri

2015-03-01

Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. Copyright © 2014. Published by Elsevier Inc.

A Hierarchical Model for Simultaneous Detection and Estimation in Multi-subject fMRI Studies

PubMed Central

Degras, David; Lindquist, Martin A.

2014-01-01

In this paper we introduce a new hierarchical model for the simultaneous detection of brain activation and estimation of the shape of the hemodynamic response in multi-subject fMRI studies. The proposed approach circumvents a major stumbling block in standard multi-subject fMRI data analysis, in that it both allows the shape of the hemodynamic response function to vary across region and subjects, while still providing a straightforward way to estimate population-level activation. An e cient estimation algorithm is presented, as is an inferential framework that not only allows for tests of activation, but also for tests for deviations from some canonical shape. The model is validated through simulations and application to a multi-subject fMRI study of thermal pain. PMID:24793829

Multiscale Analysis of Head Impacts in Contact Sports

NASA Astrophysics Data System (ADS)

Guttag, Mark; Sett, Subham; Franck, Jennifer; McNamara, Kyle; Bar-Kochba, Eyal; Crisco, Joseph; Blume, Janet; Franck, Christian

2012-02-01

Traumatic brain injury (TBI) is one of the world's major causes of death and disability. To aid companies in designing safer and improved protective gear and to aid the medical community in producing improved quantitative TBI diagnosis and assessment tools, a multiscale finite element model of the human brain, head and neck is being developed. Recorded impact data from football and hockey helmets instrumented with accelerometers are compared to simulated impact data in the laboratory. Using data from these carefully constructed laboratory experiments, we can quantify impact location, magnitude, and linear and angular accelerations of the head. The resultant forces and accelerations are applied to a fully meshed head-form created from MRI data by Simpleware. With appropriate material properties for each region of the head-form, the Abaqus finite element model can determine the stresses, strains, and deformations in the brain. Simultaneously, an in-vitro cellular TBI criterion is being developed to be incorporated into Abaqus models for the brain. The cell-based injury criterion functions the same way that damage criteria for metals and other materials are used to predict failure in structural materials.

An integrated scheme for the simultaneous determination of biogenic amines, precursor amino acids, and related metabolites by liquid chromatography with electrochemical detection.

PubMed

Oka, K; Kojima, K; Togari, A; Nagatsu, T; Kiss, B

1984-06-08

A new method using high-performance liquid chromatography with electrochemical detection (HPLC-ED) for the simultaneous determination of monoamines, their precursor amino acids, and related major metabolites in small samples of brain tissue weighing from 0.5 to 50 mg is described. The method is based on the preliminary isolation of monoamines (dopamine, norepinephrine, epinephrine, and serotonin), their precursor amino acids (tyrosine, 3,4-dihydroxyphenylalanine, tryptophan and 5-hydroxytryptophan), and their major metabolites (3-methoxytyramine, normetanephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid) by chromatography on small columns of Amberlite CG-50 and Dowex 50W, and by ethyl acetate extraction. All the compounds in the four isolated fractions were measured by HPLC-ED on a reversed-phase column under four different conditions. The sensitivity was from 0.1 to 40 pmol, depending on the substances analysed. This newly established method was applied to the study of the effects of an aromatic L-amino acid decarboxylase inhibitor (NSD-1015) and a monoamine oxidase inhibitor (pargyline) on the levels of monoamines, their precursor amino acids and their major metabolites in brain regions of mice.

Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baczko, K.; Liebert, U.G.; Billeter, M.

1986-08-01

The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the bran sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in themore » different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.« less

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

PubMed

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

Localizing Pain Matrix and Theory of Mind networks with both verbal and non-verbal stimuli.

PubMed

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.

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

PubMed Central

Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

2016-01-01

Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

Human brain mapping: A systematic comparison of parcellation methods for the human cerebral cortex.

PubMed

Arslan, Salim; Ktena, Sofia Ira; Makropoulos, Antonios; Robinson, Emma C; Rueckert, Daniel; Parisot, Sarah

2018-04-15

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously. Copyright © 2017 Elsevier Inc. All rights reserved.

The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

PubMed

Thompson, Garth J; Riedl, Valentin; Grimmer, Timo; Drzezga, Alexander; Herman, Peter; Hyder, Fahmeed

2016-07-01

The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states.

Role of Lactobacillus plantarum MTCC1325 in membrane-bound transport ATPases system in Alzheimer’s disease-induced rat brain

PubMed Central

Mallikarjuna, Nimgampalle; Praveen, Kukkarasapalli; Yellamma, Kuna

2016-01-01

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder, clinically characterized by memory dysfunction and progressive loss of cognition. No curative therapeutic or drug is available for the complete cure of this disease. The present study was aimed to evaluate the efficacy of Lactobacillus plantarum MTCC1325 in ATPases activity in the selected brain regions of rats induced with Alzheimer’s. Methods: For the study, 48 healthy Wistar rats were divided into four groups: group I as control group, group II as AD model (AD induced by intraperitoneal injection of D-Galactose, 120 mg/kg body weight for 6 weeks), group III as normal control rats which were orally administered only with L. plantarum MTCC1325 for 60 days, and group IV where the AD-induced rats simultaneously received oral treatment of L. plantarum MTCC1325 (10ml/kg body weight, 12×108 CFU/mL) for 60 days. The well known membrane bound transport enzymes including Na+, K+-ATPases, Ca2+-ATPases, and Mg2+-ATPases were assayed in the selected brain regions of hippocampus and cerebral cortex in all four groups of rats at selected time intervals. Results: Chronic injection of D-Galactose caused lipid peroxidation, oxidative stress, and mitochondrial dysfunction leading to the damage of neurons in the brain, finally bringing a significant decrease (-20%) in the brain total membrane bound ATPases over the controls. Contrary to this, treatment of AD-induced rats with L. plantarum MTCC1325 reverted all the constituents of ATPase enzymes to near normal levels within 30 days. Conclusion: Lactobacillus plantarum MTCC1325 exerted a beneficial action on the entire ATPases system in AD-induced rat brain by delaying neurodegeneration. PMID:28265536

Robust generative asymmetric GMM for brain MR image segmentation.

PubMed

Ji, Zexuan; Xia, Yong; Zheng, Yuhui

2017-11-01

Accurate segmentation of brain tissues from magnetic resonance (MR) images based on the unsupervised statistical models such as Gaussian mixture model (GMM) has been widely studied during last decades. However, most GMM based segmentation methods suffer from limited accuracy due to the influences of noise and intensity inhomogeneity in brain MR images. To further improve the accuracy for brain MR image segmentation, this paper presents a Robust Generative Asymmetric GMM (RGAGMM) for simultaneous brain MR image segmentation and intensity inhomogeneity correction. First, we develop an asymmetric distribution to fit the data shapes, and thus construct a spatial constrained asymmetric model. Then, we incorporate two pseudo-likelihood quantities and bias field estimation into the model's log-likelihood, aiming to exploit the neighboring priors of within-cluster and between-cluster and to alleviate the impact of intensity inhomogeneity, respectively. Finally, an expectation maximization algorithm is derived to iteratively maximize the approximation of the data log-likelihood function to overcome the intensity inhomogeneity in the image and segment the brain MR images simultaneously. To demonstrate the performances of the proposed algorithm, we first applied the proposed algorithm to a synthetic brain MR image to show the intermediate illustrations and the estimated distribution of the proposed algorithm. The next group of experiments is carried out in clinical 3T-weighted brain MR images which contain quite serious intensity inhomogeneity and noise. Then we quantitatively compare our algorithm to state-of-the-art segmentation approaches by using Dice coefficient (DC) on benchmark images obtained from IBSR and BrainWeb with different level of noise and intensity inhomogeneity. The comparison results on various brain MR images demonstrate the superior performances of the proposed algorithm in dealing with the noise and intensity inhomogeneity. In this paper, the RGAGMM algorithm is proposed which can simply and efficiently incorporate spatial constraints into an EM framework to simultaneously segment brain MR images and estimate the intensity inhomogeneity. The proposed algorithm is flexible to fit the data shapes, and can simultaneously overcome the influence of noise and intensity inhomogeneity, and hence is capable of improving over 5% segmentation accuracy comparing with several state-of-the-art algorithms. Copyright © 2017 Elsevier B.V. All rights reserved.

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

PubMed

Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

2017-10-21

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Robust prediction of individual creative ability from brain functional connectivity.

PubMed

Beaty, Roger E; Kenett, Yoed N; Christensen, Alexander P; Rosenberg, Monica D; Benedek, Mathias; Chen, Qunlin; Fink, Andreas; Qiu, Jiang; Kwapil, Thomas R; Kane, Michael J; Silvia, Paul J

2018-01-30

People's ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a recently developed method in functional brain imaging analysis-connectome-based predictive modeling-to identify a brain network associated with high-creative ability, using functional magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in a classic divergent thinking task. At the behavioral level, we found a strong correlation between creative thinking ability and self-reported creative behavior and accomplishment in the arts and sciences ( r = 0.54). At the neural level, we found a pattern of functional brain connectivity related to high-creative thinking ability consisting of frontal and parietal regions within default, salience, and executive brain systems. In a leave-one-out cross-validation analysis, we show that this neural model can reliably predict the creative quality of ideas generated by novel participants within the sample. Furthermore, in a series of external validation analyses using data from two independent task fMRI samples and a large task-free resting-state fMRI sample, we demonstrate robust prediction of individual creative thinking ability from the same pattern of brain connectivity. The findings thus reveal a whole-brain network associated with high-creative ability comprised of cortical hubs within default, salience, and executive systems-intrinsic functional networks that tend to work in opposition-suggesting that highly creative people are characterized by the ability to simultaneously engage these large-scale brain networks.

Whole-central nervous system functional imaging in larval Drosophila

PubMed Central

Lemon, William C.; Pulver, Stefan R.; Höckendorf, Burkhard; McDole, Katie; Branson, Kristin; Freeman, Jeremy; Keller, Philipp J.

2015-01-01

Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID:26263051

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep.

PubMed

Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E

2014-01-01

The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy. © 2013.

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

PubMed Central

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

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

PubMed

Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

2015-04-01

In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Detection of motor execution using a hybrid fNIRS-biosignal BCI: a feasibility study

PubMed Central

2013-01-01

Background Brain-computer interfaces (BCIs) were recently recognized as a method to promote neuroplastic effects in motor rehabilitation. The core of a BCI is a decoding stage by which signals from the brain are classified into different brain-states. The goal of this paper was to test the feasibility of a single trial classifier to detect motor execution based on signals from cortical motor regions, measured by functional near-infrared spectroscopy (fNIRS), and the response of the autonomic nervous system. An approach that allowed for individually tuned classifier topologies was opted for. This promises to be a first step towards a novel form of active movement therapy that could be operated and controlled by paretic patients. Methods Seven healthy subjects performed repetitions of an isometric finger pinching task, while changes in oxy- and deoxyhemoglobin concentrations were measured in the contralateral primary motor cortex and ventral premotor cortex using fNIRS. Simultaneously, heart rate, breathing rate, blood pressure and skin conductance response were measured. Hidden Markov models (HMM) were used to classify between active isometric pinching phases and rest. The classification performance (accuracy, sensitivity and specificity) was assessed for two types of input data: (i) fNIRS-signals only and (ii) fNIRS- and biosignals combined. Results fNIRS data were classified with an average accuracy of 79.4%, which increased significantly to 88.5% when biosignals were also included (p=0.02). Comparable increases were observed for the sensitivity (from 78.3% to 87.2%, p=0.008) and specificity (from 80.5% to 89.9%, p=0.062). Conclusions This study showed, for the first time, promising classification results with hemodynamic fNIRS data obtained from motor regions and simultaneously acquired biosignals. Combining fNIRS data with biosignals has a beneficial effect, opening new avenues for the development of brain-body-computer interfaces for rehabilitation applications. Further research is required to identify the contribution of each modality to the decoding capability of the subject’s hemodynamic and physiological state. PMID:23336819

Quantification of regional cerebral blood flow and volume with dynamic susceptibility contrast-enhanced MR imaging.

PubMed

Rempp, K A; Brix, G; Wenz, F; Becker, C R; Gückel, F; Lorenz, W J

1994-12-01

Quantification of regional cerebral blood flow (rCBF) and volume (rCBV) with dynamic magnetic resonance (MR) imaging. After bolus administration of a paramagnetic contrast medium, rapid T2*-weighted gradient-echo images of two sections were acquired for the simultaneous creation of concentration-time curves in the brain-feeding arteries and in brain tissue. Absolute rCBF and rCBV values were determined for gray and white brain matter in 12 subjects with use of principles of the indicator dilution theory. The mean rCBF value in gray matter was 69.7 mL/min +/- 29.7 per 100 g tissue and in white matter, 33.6 mL/min +/- 11.5 per 100 g tissue; the average rCBV was 8.0 mL +/- 3.1 per 100 g tissue and 4.2 mL +/- 1.0 per 100 g tissue, respectively. An age-related decrease in rCBF and rCBV for gray and white matter was observed. Preliminary data demonstrate that the proposed technique allows the quantification of rCBF and rCBV. Although the results are in good agreement with data from positron emission tomography studies, further evaluation is needed to establish the validity of method.

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

PubMed Central

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

PubMed

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

The functional organization of human epileptic hippocampus

PubMed Central

Klimes, Petr; Duque, Juliano J.; Brinkmann, Ben; Van Gompel, Jamie; Stead, Matt; St. Louis, Erik K.; Halamek, Josef; Jurak, Pavel

2016-01-01

The function and connectivity of human brain is disrupted in epilepsy. We previously reported that the region of epileptic brain generating focal seizures, i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding brain regions in focal neocortical epilepsy. The modulatory effect of behavioral state on the spatial and spectral scales over which the reduced functional connectivity occurs, however, is unclear. Here we use simultaneous sleep staging from scalp EEG with intracranial EEG recordings from medial temporal lobe to investigate how behavioral state modulates the spatial and spectral scales of local field potential synchrony in focal epileptic hippocampus. The local field spectral power and linear correlation between adjacent electrodes provide measures of neuronal population synchrony at different spatial scales, ∼1 and 10 mm, respectively. Our results show increased connectivity inside the SOZ and low connectivity between electrodes in SOZ and outside the SOZ. During slow-wave sleep, we observed decreased connectivity for ripple and fast ripple frequency bands within the SOZ at the 10 mm spatial scale, while the local synchrony remained high at the 1 mm spatial scale. Further study of these phenomena may prove useful for SOZ localization and help understand seizure generation, and the functional deficits seen in epileptic eloquent cortex. PMID:27030735

A novel fiber-free technique for brain activity imaging in multiple freely behaving mice

NASA Astrophysics Data System (ADS)

Inagaki, Shigenori; Agetsuma, Masakazu; Nagai, Takeharu

2018-02-01

Brain functions and related psychiatric disorders have been investigated by recording electrophysiological field potential. When recording it, a conventional method requires fiber-based apparatus connected to the brain, which however hampers the simultaneous measurement in multiple animals (e.g. by a tangle of fibers). Here, we propose a fiber-free recording technique in conjunction with a ratiometric bioluminescent voltage indicator. Our method allows investigation of electrophysiological filed potential dynamics in multiple freely behaving animals simultaneously over a long time period. Therefore, this fiber-free technique opens up the way to investigate a new mechanism of brain function that governs social behaviors and animal-to-animal interaction.

Rich-Club Organization in Effective Connectivity among Cortical Neurons.

PubMed

Nigam, Sunny; Shimono, Masanori; Ito, Shinya; Yeh, Fang-Chin; Timme, Nicholas; Myroshnychenko, Maxym; Lapish, Christopher C; Tosi, Zachary; Hottowy, Pawel; Smith, Wesley C; Masmanidis, Sotiris C; Litke, Alan M; Sporns, Olaf; Beggs, John M

2016-01-20

The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar to in vivo reports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a "rich club." We found similar results in networks recorded in vivo from rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory. Significance statement: Many studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several hundred at a time) with such high temporal resolution (so we can know the direction of communication between neurons) for mapping networks within cortex. We found that information was not transferred equally through all neurons. Instead, ∼70% of the information passed through only 20% of the neurons. Network models suggest that this highly concentrated pattern of information transfer would be both efficient and robust to damage. Therefore, this work may help in understanding how the cortex processes information and responds to neurodegenerative diseases. Copyright © 2016 Nigam et al.

Rich-Club Organization in Effective Connectivity among Cortical Neurons

PubMed Central

Shimono, Masanori; Ito, Shinya; Yeh, Fang-Chin; Timme, Nicholas; Myroshnychenko, Maxym; Lapish, Christopher C.; Tosi, Zachary; Hottowy, Pawel; Smith, Wesley C.; Masmanidis, Sotiris C.; Litke, Alan M.; Sporns, Olaf; Beggs, John M.

2016-01-01

The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar to in vivo reports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a “rich club.” We found similar results in networks recorded in vivo from rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory. SIGNIFICANCE STATEMENT Many studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several hundred at a time) with such high temporal resolution (so we can know the direction of communication between neurons) for mapping networks within cortex. We found that information was not transferred equally through all neurons. Instead, ∼70% of the information passed through only 20% of the neurons. Network models suggest that this highly concentrated pattern of information transfer would be both efficient and robust to damage. Therefore, this work may help in understanding how the cortex processes information and responds to neurodegenerative diseases. PMID:26791200

Single-trial EEG-informed fMRI analysis of emotional decision problems in hot executive function.

PubMed

Guo, Qian; Zhou, Tiantong; Li, Wenjie; Dong, Li; Wang, Suhong; Zou, Ling

2017-07-01

Executive function refers to conscious control in psychological process which relates to thinking and action. Emotional decision is a part of hot executive function and contains emotion and logic elements. As a kind of important social adaptation ability, more and more attention has been paid in recent years. Gambling task can be well performed in the study of emotional decision. As fMRI researches focused on gambling task show not completely consistent brain activation regions, this study adopted EEG-fMRI fusion technology to reveal brain neural activity related with feedback stimuli. In this study, an EEG-informed fMRI analysis was applied to process simultaneous EEG-fMRI data. First, relative power-spectrum analysis and K-means clustering method were performed separately to extract EEG-fMRI features. Then, Generalized linear models were structured using fMRI data and using different EEG features as regressors. The results showed that in the win versus loss stimuli, the activated regions almost covered the caudate, the ventral striatum (VS), the orbital frontal cortex (OFC), and the cingulate. Wide activation areas associated with reward and punishment were revealed by the EEG-fMRI integration analysis than the conventional fMRI results, such as the posterior cingulate and the OFC. The VS and the medial prefrontal cortex (mPFC) were found when EEG power features were performed as regressors of GLM compared with results entering the amplitudes of feedback-related negativity (FRN) as regressors. Furthermore, the brain region activation intensity was the strongest when theta-band power was used as a regressor compared with the other two fusion results. The EEG-based fMRI analysis can more accurately depict the whole-brain activation map and analyze emotional decision problems.

Neuronal Assemblies Evidence Distributed Interactions within a Tactile Discrimination Task in Rats

PubMed Central

Deolindo, Camila S.; Kunicki, Ana C. B.; da Silva, Maria I.; Lima Brasil, Fabrício; Moioli, Renan C.

2018-01-01

Accumulating evidence suggests that neural interactions are distributed and relate to animal behavior, but many open questions remain. The neural assembly hypothesis, formulated by Hebb, states that synchronously active single neurons may transiently organize into functional neural circuits—neuronal assemblies (NAs)—and that would constitute the fundamental unit of information processing in the brain. However, the formation, vanishing, and temporal evolution of NAs are not fully understood. In particular, characterizing NAs in multiple brain regions over the course of behavioral tasks is relevant to assess the highly distributed nature of brain processing. In the context of NA characterization, active tactile discrimination tasks with rats are elucidative because they engage several cortical areas in the processing of information that are otherwise masked in passive or anesthetized scenarios. In this work, we investigate the dynamic formation of NAs within and among four different cortical regions in long-range fronto-parieto-occipital networks (primary somatosensory, primary visual, prefrontal, and posterior parietal cortices), simultaneously recorded from seven rats engaged in an active tactile discrimination task. Our results first confirm that task-related neuronal firing rate dynamics in all four regions is significantly modulated. Notably, a support vector machine decoder reveals that neural populations contain more information about the tactile stimulus than the majority of single neurons alone. Then, over the course of the task, we identify the emergence and vanishing of NAs whose participating neurons are shown to contain more information about animal behavior than randomly chosen neurons. Taken together, our results further support the role of multiple and distributed neurons as the functional unit of information processing in the brain (NA hypothesis) and their link to active animal behavior. PMID:29375324

A new methodical approach in neuroscience: assessing inter-personal brain coupling using functional near-infrared imaging (fNIRI) hyperscanning.

PubMed

Scholkmann, Felix; Holper, Lisa; Wolf, Ursula; Wolf, Martin

2013-11-27

Since the first demonstration of how to simultaneously measure brain activity using functional magnetic resonance imaging (fMRI) on two subjects about 10 years ago, a new paradigm in neuroscience is emerging: measuring brain activity from two or more people simultaneously, termed "hyperscanning". The hyperscanning approach has the potential to reveal inter-personal brain mechanisms underlying interaction-mediated brain-to-brain coupling. These mechanisms are engaged during real social interactions, and cannot be captured using single-subject recordings. In particular, functional near-infrared imaging (fNIRI) hyperscanning is a promising new method, offering a cost-effective, easy to apply and reliable technology to measure inter-personal interactions in a natural context. In this short review we report on fNIRI hyperscanning studies published so far and summarize opportunities and challenges for future studies.

Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

PubMed Central

Diukova, Ana; Ware, Jennifer; Smith, Jessica E.; Evans, C. John; Murphy, Kevin; Rogers, Peter J.; Wise, Richard G.

2012-01-01

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG–FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis. PMID:22561357

Cognitive Flexibility through Metastable Neural Dynamics Is Disrupted by Damage to the Structural Connectome.

PubMed

Hellyer, Peter J; Scott, Gregory; Shanahan, Murray; Sharp, David J; Leech, Robert

2015-06-17

Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome. Copyright © 2015 the authors 0270-6474/15/359050-14$15.00/0.

Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression.

PubMed

Haenisch, Britta; Bilkei-Gorzo, Andras; Caron, Marc G; Bönisch, Heinz

2009-10-01

Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, nerve growth factor, and neurotrophin-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NET knock out (NETKO) mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.

A mass spectrometry imaging approach for investigating how drug-drug interactions influence drug blood-brain barrier permeability.

PubMed

Vallianatou, Theodosia; Strittmatter, Nicole; Nilsson, Anna; Shariatgorji, Mohammadreza; Hamm, Gregory; Pereira, Marcela; Källback, Patrik; Svenningsson, Per; Karlgren, Maria; Goodwin, Richard J A; Andrén, Per E

2018-05-15

There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies. Copyright © 2018. Published by Elsevier Inc.

Cerebral Microcirculation during Experimental Normovolaemic Anemia

PubMed Central

Bellapart, Judith; Cuthbertson, Kylie; Dunster, Kimble; Diab, Sara; Platts, David G.; Raffel, O. Christopher; Gabrielian, Levon; Barnett, Adrian; Paratz, Jenifer; Boots, Rob; Fraser, John F.

2016-01-01

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia. Experimental studies suggest that anemia leads to cerebral hypoxia and increased rates of infarction, but the lack of clinical equipoise, when testing the cerebral effects of transfusion among critically injured patients, supports the need of experimental studies. The aim of this study was to quantify cerebral microcirculation and the potential presence of axonal damage in an experimental model exposed to normovolaemic anemia, with the intention of describing possible limitations within management practices in critically ill patients. Under non-recovered anesthesia, six Merino sheep were instrumented using an intracardiac transeptal catheter to inject coded microspheres into the left atrium to ensure systemic and non-chaotic distribution. Cytometric analyses quantified cerebral microcirculation at specific regions of the brain. Amyloid precursor protein staining was used as an indicator of axonal damage. Animals were exposed to normovolaemic anemia by blood extractions from the indwelling arterial catheter with simultaneous fluid replacement through a venous central catheter. Simultaneous data recording from cerebral tissue oxygenation, intracranial pressure, and cardiac output was monitored. A regression model was used to examine the effects of anemia on microcirculation with a mixed model to control for repeated measures. Homogeneous and normal cerebral microcirculation with no evidence of axonal damage was present in all cerebral regions, with no temporal variability, concluding that acute normovolaemic anemia does not result in short-term effects on cerebral microcirculation in the ovine brain. PMID:26869986

Cognitive function and retinal and ischemic brain changes

PubMed Central

Espeland, M.A.; Klein, B.E.; Casanova, R.; Gaussoin, S.A.; Jackson, R.D.; Millen, A.E.; Resnick, S.M.; Rossouw, J.E.; Shumaker, S.A.; Wallace, R.; Yaffe, K.

2012-01-01

Objective: To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women. Methods: This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000–2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996–2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia. Results: Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy. Conclusions: The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes. PMID:22422889

The ultrasound brain helmet: early human feasibility study of multiple simultaneous 3D scans of cerebral vasculature

NASA Astrophysics Data System (ADS)

Lindsey, Brooks D.; Ivancevich, Nikolas M.; Whitman, John; Light, Edward; Fronheiser, Matthew; Nicoletto, Heather A.; Laskowitz, Daniel T.; Smith, Stephen W.

2009-02-01

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time 3D scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64° pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128° sector, two simultaneous parasagittal images merged into a 128° × 64° C-mode plane, and a simultaneous 64° axial image. Real-time 3D color Doppler images acquired in initial clinical studies after contrast injection demonstrate flow in several representative blood vessels. An offline Doppler rendering of data from two transducers simultaneously scanning via the temporal windows provides an early visualization of the flow in vessels on both sides of the brain. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission, thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

Narcolepsy: regional cerebral blood flow during sleep and wakefulness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, F.; Meyer, J.S.; Karacan, I.

Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less than waking values. Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar, right inferior temporal, and bilateral frontal regions. In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +- 13 ml per 100 gm brain per minute. During REMmore » sleep, mean hemispheric Fg increased concurrently with large increases in brainstem-cerebellar region flow. During stages I and II sleep without REM, there were significant increases in mean hemispheric Fg and brainstem-cerebellar Fg, just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.« less

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Thinking about thinking: Neural mechanisms and effects on memory.

PubMed

Bonhage, Corinna; Weber, Friederike; Exner, Cornelia; Kanske, Philipp

2016-02-15

It is a well-established finding that memory encoding is impaired if an external secondary task (e.g. tone discrimination) is performed simultaneously. Yet, while studying we are also often engaged in internal secondary tasks such as planning, ruminating, or daydreaming. It remains unclear whether such a secondary internal task has similar effects on memory and what the neural mechanisms underlying such an influence are. We therefore measured participants' blood oxygenation level dependent responses while they learned word-pairs and simultaneously performed different types of secondary tasks (i.e., internal, external, and control). Memory performance decreased in both internal and external secondary tasks compared to the easy control condition. However, while the external task reduced activity in memory-encoding related regions (hippocampus), the internal task increased neural activity in brain regions associated with self-reflection (anterior medial prefrontal cortex), as well as in regions associated with performance monitoring and the perception of salience (anterior insula, dorsal anterior cingulate cortex). Resting-state functional connectivity analyses confirmed that anterior medial prefrontal cortex and anterior insula/dorsal anterior cingulate cortex are part of the default mode network and salience network, respectively. In sum, a secondary internal task impairs memory performance just as a secondary external task, but operates through different neural mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Method for simultaneous imaging of endogenous low molecular weight metabolites in mouse brain using TiO2 nanoparticles in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry.

PubMed

Shrivas, Kamlesh; Hayasaka, Takahiro; Sugiura, Yuki; Setou, Mitsutoshi

2011-10-01

We report the detection of a group of endogenous low molecular weight metabolites (LMWM) in mouse brain (80-500 Da) using TiO(2) nanoparticles (NPs) in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry (Nano-PALDI-IMS) without any washing and separation step prior to MS analysis. The identification of metabolites using TiO(2) NPs was compared with a conventional organic matrix 2,5-dihydroxybenzoic acid (DHB) where signals of 179 molecules were specific to TiO(2) NPs, 4 were specific to DHB, and 21 were common to both TiO(2) NPs and DHB. The use of TiO(2) NPs enabled the detection of a higher number of LMWM as compared to DHB and gold NPs as a matrix. This approach is a simple, inexpensive, washing, and separation free for imaging and identification of LMWM in mouse brain. We believe that the biochemical information from distinct regions of the brain using a Nano-PALDI-IMS will be helpful in elucidating the imbalances linked with diseases in biomedical samples.

Deep brain optical measurements of cell type-specific neural activity in behaving mice.

PubMed

Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M

2014-01-01

Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca(2+) indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior.

Whole brain diffeomorphic metric mapping via integration of sulcal and gyral curves, cortical surfaces, and images

PubMed Central

Du, Jia; Younes, Laurent; Qiu, Anqi

2011-01-01

This paper introduces a novel large deformation diffeomorphic metric mapping algorithm for whole brain registration where sulcal and gyral curves, cortical surfaces, and intensity images are simultaneously carried from one subject to another through a flow of diffeomorphisms. To the best of our knowledge, this is the first time that the diffeomorphic metric from one brain to another is derived in a shape space of intensity images and point sets (such as curves and surfaces) in a unified manner. We describe the Euler–Lagrange equation associated with this algorithm with respect to momentum, a linear transformation of the velocity vector field of the diffeomorphic flow. The numerical implementation for solving this variational problem, which involves large-scale kernel convolution in an irregular grid, is made feasible by introducing a class of computationally friendly kernels. We apply this algorithm to align magnetic resonance brain data. Our whole brain mapping results show that our algorithm outperforms the image-based LDDMM algorithm in terms of the mapping accuracy of gyral/sulcal curves, sulcal regions, and cortical and subcortical segmentation. Moreover, our algorithm provides better whole brain alignment than combined volumetric and surface registration (Postelnicu et al., 2009) and hierarchical attribute matching mechanism for elastic registration (HAMMER) (Shen and Davatzikos, 2002) in terms of cortical and subcortical volume segmentation. PMID:21281722

A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor.

PubMed

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.

Simultaneous measurement of glucose transport and utilization in the human brain

PubMed Central

Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

Simultaneous EEG and MEG source reconstruction in sparse electromagnetic source imaging.

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

Brain Tumor Segmentation Using Convolutional Neural Networks in MRI Images.

PubMed

Pereira, Sergio; Pinto, Adriano; Alves, Victor; Silva, Carlos A

2016-05-01

Among brain tumors, gliomas are the most common and aggressive, leading to a very short life expectancy in their highest grade. Thus, treatment planning is a key stage to improve the quality of life of oncological patients. Magnetic resonance imaging (MRI) is a widely used imaging technique to assess these tumors, but the large amount of data produced by MRI prevents manual segmentation in a reasonable time, limiting the use of precise quantitative measurements in the clinical practice. So, automatic and reliable segmentation methods are required; however, the large spatial and structural variability among brain tumors make automatic segmentation a challenging problem. In this paper, we propose an automatic segmentation method based on Convolutional Neural Networks (CNN), exploring small 3 ×3 kernels. The use of small kernels allows designing a deeper architecture, besides having a positive effect against overfitting, given the fewer number of weights in the network. We also investigated the use of intensity normalization as a pre-processing step, which though not common in CNN-based segmentation methods, proved together with data augmentation to be very effective for brain tumor segmentation in MRI images. Our proposal was validated in the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013), obtaining simultaneously the first position for the complete, core, and enhancing regions in Dice Similarity Coefficient metric (0.88, 0.83, 0.77) for the Challenge data set. Also, it obtained the overall first position by the online evaluation platform. We also participated in the on-site BRATS 2015 Challenge using the same model, obtaining the second place, with Dice Similarity Coefficient metric of 0.78, 0.65, and 0.75 for the complete, core, and enhancing regions, respectively.

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

PubMed Central

Chang, Eric H.; Frattini, Stephen A.; Robbiati, Sergio; Huerta, Patricio T.

2013-01-01

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain. PMID:23851569

Intracranial spectral amplitude dynamics of perceptual suppression in fronto-insular, occipito-temporal, and primary visual cortex

PubMed Central

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

Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR

NASA Astrophysics Data System (ADS)

Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander

2017-04-01

In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This work demonstrates that inaccuracies in attenuation maps can induce bias in dynamic brain PET studies. Multi-atlas attenuation correction with MaxProb enables quantification on hybrid PET-MR scanners, eschewing the need for CT.

Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR.

PubMed

Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A; Costes, Nicolas; Hammers, Alexander

2017-04-07

In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [ 18 F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [ 18 F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BP ND ). On static [ 18 F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [ 18 F]MPPF, most regional errors on BP ND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This work demonstrates that inaccuracies in attenuation maps can induce bias in dynamic brain PET studies. Multi-atlas attenuation correction with MaxProb enables quantification on hybrid PET-MR scanners, eschewing the need for CT.

Words in Context: The Effects of Length, Frequency, and Predictability on Brain Responses During Natural Reading

PubMed Central

Schuster, Sarah; Hawelka, Stefan; Hutzler, Florian; Kronbichler, Martin; Richlan, Fabio

2016-01-01

Word length, frequency, and predictability count among the most influential variables during reading. Their effects are well-documented in eye movement studies, but pertinent evidence from neuroimaging primarily stem from single-word presentations. We investigated the effects of these variables during reading of whole sentences with simultaneous eye-tracking and functional magnetic resonance imaging (fixation-related fMRI). Increasing word length was associated with increasing activation in occipital areas linked to visual analysis. Additionally, length elicited a U-shaped modulation (i.e., least activation for medium-length words) within a brain stem region presumably linked to eye movement control. These effects, however, were diminished when accounting for multiple fixation cases. Increasing frequency was associated with decreasing activation within left inferior frontal, superior parietal, and occipito-temporal regions. The function of the latter region—hosting the putative visual word form area—was originally considered as limited to sublexical processing. An exploratory analysis revealed that increasing predictability was associated with decreasing activation within middle temporal and inferior frontal regions previously implicated in memory access and unification. The findings are discussed with regard to their correspondence with findings from single-word presentations and with regard to neurocognitive models of visual word recognition, semantic processing, and eye movement control during reading. PMID:27365297

Penetrating the Blood-Brain Barrier: Promise of Novel Nanoplatforms and Delivery Vehicles.

PubMed

Ali, Iqbal Unnisa; Chen, Xiaoyuan

2015-10-27

Multifunctional nanoplatforms combining versatile therapeutic modalities with a variety of imaging options have the potential to diagnose, monitor, and treat brain diseases. The promise of nanotechnology can only be realized by the simultaneous development of innovative brain-targeting delivery vehicles capable of penetrating the blood-brain barrier without compromising its structural integrity.

The Relationship between Simultaneous-Successive Processing and Academic Achievement.

ERIC Educational Resources Information Center

Merritt, Frank M.; McCallum, Steve

The Luria-Das Information Processing Model of human learning holds that information is analysed and coded within the brain in either a simultaneous or a successive fashion. Simultaneous integration refers to the synthesis of separate elements into groups, often with spatial characteristics; successive integration means that information is…

Relationship of Neurovascular Elements to Neuron Injury during Ischemia

PubMed Central

del Zoppo, Gregory J.

2009-01-01

Occlusion of flow to the brain regions identifies regions of vulnerability within the vascular territory at risk, which coalesce to become the mature ischemic lesion. A large number of unsuccessful clinical trials have focused on neuron and extravascular targets in humans that have shown apparent salvage in preclinical models. However, the observation that microvessel and neuron responses to ischemia occur simultaneously in these regions suggest that the responses could be coordinated. This presentation examines evidence in support of the conceptual ‘neurovascular unit’ and its application to the setting of acute intervention trials in ischemic stroke. There are no uniform reasons for which nonvascular interventions, as a class, have not been successful in clinical trials, but both the clinical observations and the hypothesis imply the need to understand interactions with the neurovascular unit as a prelude to further neuron protectant trials. PMID:19342834

Event-related potentials and secondary task performance during simulated driving.

PubMed

Wester, A E; Böcker, K B E; Volkerts, E R; Verster, J C; Kenemans, J L

2008-01-01

Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.

Discover mouse gene coexpression landscapes using dictionary learning and sparse coding.

PubMed

Li, Yujie; Chen, Hanbo; Jiang, Xi; Li, Xiang; Lv, Jinglei; Peng, Hanchuan; Tsien, Joe Z; Liu, Tianming

2017-12-01

Gene coexpression patterns carry rich information regarding enormously complex brain structures and functions. Characterization of these patterns in an unbiased, integrated, and anatomically comprehensive manner will illuminate the higher-order transcriptome organization and offer genetic foundations of functional circuitry. Here using dictionary learning and sparse coding, we derived coexpression networks from the space-resolved anatomical comprehensive in situ hybridization data from Allen Mouse Brain Atlas dataset. The key idea is that if two genes use the same dictionary to represent their original signals, then their gene expressions must share similar patterns, thereby considering them as "coexpressed." For each network, we have simultaneous knowledge of spatial distributions, the genes in the network and the extent a particular gene conforms to the coexpression pattern. Gene ontologies and the comparisons with published gene lists reveal biologically identified coexpression networks, some of which correspond to major cell types, biological pathways, and/or anatomical regions.

PORTR: Pre-Operative and Post-Recurrence Brain Tumor Registration

PubMed Central

Niethammer, Marc; Akbari, Hamed; Bilello, Michel; Davatzikos, Christos; Pohl, Kilian M.

2014-01-01

We propose a new method for deformable registration of pre-operative and post-recurrence brain MR scans of glioma patients. Performing this type of intra-subject registration is challenging as tumor, resection, recurrence, and edema cause large deformations, missing correspondences, and inconsistent intensity profiles between the scans. To address this challenging task, our method, called PORTR, explicitly accounts for pathological information. It segments tumor, resection cavity, and recurrence based on models specific to each scan. PORTR then uses the resulting maps to exclude pathological regions from the image-based correspondence term while simultaneously measuring the overlap between the aligned tumor and resection cavity. Embedded into a symmetric registration framework, we determine the optimal solution by taking advantage of both discrete and continuous search methods. We apply our method to scans of 24 glioma patients. Both quantitative and qualitative analysis of the results clearly show that our method is superior to other state-of-the-art approaches. PMID:24595340

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

PubMed Central

Berényi, Antal; Somogyvári, Zoltán; Nagy, Anett J.; Roux, Lisa; Long, John D.; Fujisawa, Shigeyoshi; Stark, Eran; Leonardo, Anthony; Harris, Timothy D.

2013-01-01

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electroanatomic boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomic space. These methods will allow the investigation of circuit operations and behavior-dependent interregional interactions for testing hypotheses of neural networks and brain function. PMID:24353300

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

PubMed Central

Gulati, Srishti; Cao, Vania Y.; Otte, Stephani

2017-01-01

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical neurons with two-photon microscopy has provided unique insights into cortical structure, function and plasticity. However, these studies are limited to head fixed animals, greatly reducing the behavioral complexity available for study. In this paper, we describe a procedure for performing chronic fluorescence microscopy with cellular-resolution across multiple cortical layers in freely behaving mice. We used an integrated miniaturized fluorescence microscope paired with an implanted prism probe to simultaneously visualize and record the calcium dynamics of hundreds of neurons across multiple layers of the somatosensory cortex as the mouse engaged in a novel object exploration task, over several days. This technique can be adapted to other brain regions in different animal species for other behavioral paradigms. PMID:28654056

Investigation of human multiple sclerosis lesions using high resolution spectrally unmixed CARS microscopy

NASA Astrophysics Data System (ADS)

Poon, Kelvin W.; Brideau, Craig; Teo, Wulin; Schenk, Geert J.; Klaver, Roel; Klauser, Antoine M.; Kawasoe, Jean H.; Geurts, Jeroen J. G.; Stys, Peter K.

2013-03-01

The pathology of multiple sclerosis (MS) involves both the gray and white matter regions of the brain and spinal cord. It is characterized by various combinations of demyelination, inflammatory infiltration, axonal degeneration, and later gliosis in chronic lesions. While acute and chronic white matter plaques are well characterized and easily identified, evidence indicates that the CNS of MS patients may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM) and in diffusely abnormal white matter (DAWM) where histochemical stains and advanced magnetic resonance imaging indicate altered tissue composition. Thus, the prototypical acute inflammatory lesion may merely represent the most obvious manifestation of a chronic widespread involvement of the CNS, which is difficult to examine reliably. The current study deals with the microstructure and biochemistry of demyelination, remyelination and axonal loss in various regions of post-mortem human MS brain, including NAWM, areas of remyelination and more typical acute and chronic lesions. The myelin sheath, neuroglia and perivascular spaces were investigated using a novel Coherent Anti-Stokes Raman Scattering (CARS) microscope with simultaneous Two-Photon Excited Fluorescence (TPEF) imaging. The active CH stretching region between 2800 and 3000 cm-1 was probed to provide chemically specific, high resolution, label-free imaging pertaining to the progression of the disease. CARS data were correlated with TPEF and conventional histochemical and immunohistochemical stains. Our novel CARS microscopy system provides detailed morphological and biochemical information regarding CNS pathology in MS and that may be applicable to a broad range of other human brain and spinal cord disorders.

Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct measurement of drug occupancy and effects on the human brain in vivo.

PubMed

Malizia, A L; Gunn, R N; Wilson, S J; Waters, S H; Bloomfield, P M; Cunningham, V J; Nutt, D J

1996-01-01

To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of "free" drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5-50 micrograms/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta 1 spectral power on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. This last finding validates the use of other non-tomographic counting techniques (Malizia et al., 1995a) where an index of displacement can be obtained after the administration of less than 1% of the dose of radiation needed for a PET study. These studies are likely to be useful in human psychopharmacology, in particular in the assessment of tolerance and of putative changes in benzodiazepine sensitivity in anxiety disorders. The same principles can be applied to other ligand studies and will be useful to validate current PK/PD models.

Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4 T: Application to the investigation of excitotoxic lesions

NASA Astrophysics Data System (ADS)

Doan, Bich-Thuy; Autret, Gwennhael; Mispelter, Joël; Méric, Philippe; Même, William; Montécot-Dubourg, Céline; Corrèze, Jean-Loup; Szeremeta, Frédéric; Gillet, Brigitte; Beloeil, Jean-Claude

2009-05-01

13C spectroscopy combined with the injection of 13C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4 T: a bi-voxel 1H-( 13C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel 1H-( 13C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U- 13C glucose, two 1H-( 13C) spectra of distinct (4 × 4 × 4 mm 3) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two 1H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The 1H-( 13C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel 1H-( 13C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions.

A cross-modal investigation of the neural substrates for ongoing cognition

PubMed Central

Wang, Megan; He, Biyu J.

2014-01-01

What neural mechanisms underlie the seamless flow of our waking consciousness? A necessary albeit insufficient condition for such neural mechanisms is that they should be consistently modulated across time were a segment of the conscious stream to be repeated twice. In this study, we experimentally manipulated the content of a story followed by subjects during functional magnetic resonance imaging (fMRI) independently from the modality of sensory input (as visual text or auditory speech) as well as attentional focus. We then extracted brain activity patterns consistently modulated across subjects by the evolving content of the story regardless of whether it was presented visually or auditorily. Specifically, in one experiment we presented the same story to different subjects via either auditory or visual modality. In a second experiment, we presented two different stories simultaneously, one auditorily, one visually, and manipulated the subjects' attentional focus. This experimental design allowed us to dissociate brain activities underlying modality-specific sensory processing from modality-independent story processing. We uncovered a network of brain regions consistently modulated by the evolving content of a story regardless of the sensory modality used for stimulus input, including the superior temporal sulcus/gyrus (STS/STG), the inferior frontal gyrus (IFG), the posterior cingulate cortex (PCC), the medial frontal cortex (MFC), the temporal pole (TP), and the temporoparietal junction (TPJ). Many of these regions have previously been implicated in semantic processing. Interestingly, different stories elicited similar brain activity patterns, but with subtle differences potentially attributable to varying degrees of emotional valence and self-relevance. PMID:25206347

Blood-brain barrier transport of butanol and water relative to N-isopropyl-p-iodoamphetamine as the internal reference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pardridge, W.M.; Fierer, G.

1985-06-01

The literature regarding the blood--brain barrier (BBB) transport of butanol is conflicting as studies report both incomplete and complete extraction of butanol by the brain. In this work the BBB transport of both (/sup 14/C)butanol and (/sup 3/H)water was studied using the carotid injection technique in conscious and in ketamine- or pentobarbital-anesthetized rats employing N-isopropyl-p-(/sup 125/I)iodoamphetamine ((/sup 125/I)IMP) as the internal reference and as a fluid microsphere. The three isotopes (/sup 3/H, /sup 125/I, /sup 14/C) were conveniently counted simultaneously in a liquid scintillation spectrometer. IMP is essentially completely sequestered by the brain for at least 1 min in consciousmore » rats and for 2 min in anesthetized animals. Butanol extraction by rat forebrain is not flow limited but ranges between 77 +/- 1 and 87 +/- 1% for the three conditions. The permeability-surface area product/cerebral blood flow ratio of butanol and water in rat forebrain remains relatively constant, despite a twofold increase in cerebral blood flow in conscious relative to pentobarbital-anesthetized rats. The absence of an inverse relationship between flow and butanol or water extraction is consistent with capillary recruitment being the principal mechanism underlying changes in cerebral blood flow in anesthesia. The diffusion restriction of BBB transport of butanol in some regions, but not in others, necessitates a careful regional analysis of BBB permeability to butanol prior to usage of this compound as a cerebral blood flow marker.« less

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

PubMed

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.

Simultaneous measurement of glucose transport and utilization in the human brain.

PubMed

Shestov, Alexander A; Emir, Uzay E; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R; Öz, Gülin

2011-11-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, K(M)(t) and V(max)(t), in humans have so far been obtained by measuring steady-state brain glucose levels by proton ((1)H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMR(glc)) obtained from other tracer studies, such as (13)C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state (1)H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMR(glc), this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain.

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice.

PubMed

Zhou, Haibo; Liu, Junlai; Zhou, Changyang; Gao, Ni; Rao, Zhiping; Li, He; Hu, Xinde; Li, Changlin; Yao, Xuan; Shen, Xiaowen; Sun, Yidi; Wei, Yu; Liu, Fei; Ying, Wenqin; Zhang, Junming; Tang, Cheng; Zhang, Xu; Xu, Huatai; Shi, Linyu; Cheng, Leping; Huang, Pengyu; Yang, Hui

2018-03-01

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the framingham offspring study

USDA-ARS?s Scientific Manuscript database

Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury. In 3127...

Simultaneous Tc-99m and I-123 dual-radionuclide imaging with a solid-state detector-based brain-SPECT system and energy-based scatter correction.

PubMed

Takeuchi, Wataru; Suzuki, Atsuro; Shiga, Tohru; Kubo, Naoki; Morimoto, Yuichi; Ueno, Yuichiro; Kobashi, Keiji; Umegaki, Kikuo; Tamaki, Nagara

2016-12-01

A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I-lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 ± 4.0 % (mean ± standard deviation). In the six-compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 ± 11.0 and 2.3 ± 1.8 %, respectively. In the volunteer study, the PD between the single and dual acquisitions was 4.5 ± 3.4 %. This CdTe-SPECT system using the FiveEW method can provide accurate simultaneous dual-radionuclide imaging. A solid-state detector SPECT system using the FiveEW method will permit quantitative simultaneous Tc-99m and I-123 study to become clinically applicable.

Semi-automated brain tumor and edema segmentation using MRI.

PubMed

Xie, Kai; Yang, Jie; Zhang, Z G; Zhu, Y M

2005-10-01

Manual segmentation of brain tumors from magnetic resonance images is a challenging and time-consuming task. A semi-automated method has been developed for brain tumor and edema segmentation that will provide objective, reproducible segmentations that are close to the manual results. Additionally, the method segments non-enhancing brain tumor and edema from healthy tissues in magnetic resonance images. In this study, a semi-automated method was developed for brain tumor and edema segmentation and volume measurement using magnetic resonance imaging (MRI). Some novel algorithms for tumor segmentation from MRI were integrated in this medical diagnosis system. We exploit a hybrid level set (HLS) segmentation method driven by region and boundary information simultaneously, region information serves as a propagation force which is robust and boundary information serves as a stopping functional which is accurate. Ten different patients with brain tumors of different size, shape and location were selected, a total of 246 axial tumor-containing slices obtained from 10 patients were used to evaluate the effectiveness of segmentation methods. This method was applied to 10 non-enhancing brain tumors and satisfactory results were achieved. Two quantitative measures for tumor segmentation quality estimation, namely, correspondence ratio (CR) and percent matching (PM), were performed. For the segmentation of brain tumor, the volume total PM varies from 79.12 to 93.25% with the mean of 85.67+/-4.38% while the volume total CR varies from 0.74 to 0.91 with the mean of 0.84+/-0.07. For the segmentation of edema, the volume total PM varies from 72.86 to 87.29% with the mean of 79.54+/-4.18% while the volume total CR varies from 0.69 to 0.85 with the mean of 0.79+/-0.08. The HLS segmentation method perform better than the classical level sets (LS) segmentation method in PM and CR. The results of this research may have potential applications, both as a staging procedure and a method of evaluating tumor response during treatment, this method can be used as a clinical image analysis tool for doctors or radiologists.

Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by Simultaneous EEG-fMRI Recording.

PubMed

Green, Jessica J; Boehler, Carsten N; Roberts, Kenneth C; Chen, Ling-Chia; Krebs, Ruth M; Song, Allen W; Woldorff, Marty G

2017-08-16

Visual spatial attention has been studied in humans with both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) individually. However, due to the intrinsic limitations of each of these methods used alone, our understanding of the systems-level mechanisms underlying attentional control remains limited. Here, we examined trial-to-trial covariations of concurrently recorded EEG and fMRI in a cued visual spatial attention task in humans, which allowed delineation of both the generators and modulators of the cue-triggered event-related oscillatory brain activity underlying attentional control function. The fMRI activity in visual cortical regions contralateral to the cued direction of attention covaried positively with occipital gamma-band EEG, consistent with activation of cortical regions representing attended locations in space. In contrast, fMRI activity in ipsilateral visual cortical regions covaried inversely with occipital alpha-band oscillations, consistent with attention-related suppression of the irrelevant hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of these spatially specific, attention-related, oscillatory EEG modulations. Because the pulvinar's neuroanatomical geometry makes it unlikely to be a direct generator of the scalp-recorded EEG, these covariational patterns appear to reflect the pulvinar's role as a regulatory control structure, sending spatially specific signals to modulate visual cortex excitability proactively. Together, these combined EEG/fMRI results illuminate the dynamically interacting cortical and subcortical processes underlying spatial attention, providing important insight not realizable using either method alone. SIGNIFICANCE STATEMENT Noninvasive recordings of changes in the brain's blood flow using functional magnetic resonance imaging and electrical activity using electroencephalography in humans have individually shown that shifting attention to a location in space produces spatially specific changes in visual cortex activity in anticipation of a stimulus. The mechanisms controlling these attention-related modulations of sensory cortex, however, are poorly understood. Here, we recorded these two complementary measures of brain activity simultaneously and examined their trial-to-trial covariations to gain insight into these attentional control mechanisms. This multi-methodological approach revealed the attention-related coordination of visual cortex modulation by the subcortical pulvinar nucleus of the thalamus while also disentangling the mechanisms underlying the attentional enhancement of relevant stimulus input and those underlying the concurrent suppression of irrelevant input. Copyright © 2017 the authors 0270-6474/17/377803-08$15.00/0.

A Neural Mechanism of Social Categorization.

PubMed

Stolier, Ryan M; Freeman, Jonathan B

2017-06-07

Humans readily sort one another into multiple social categories from mere facial features. However, the facial features used to do so are not always clear-cut because they can be associated with opponent categories (e.g., feminine male face). Recently, computational models and behavioral studies have provided indirect evidence that categorizing such faces is accomplished through dynamic competition between parallel, coactivated social categories that resolve into a stable categorical percept. Using a novel paradigm combining fMRI with real-time hand tracking, the present study examined how the brain translates diverse social cues into categorical percepts. Participants (male and female) categorized faces varying in gender and racial typicality. When categorizing atypical faces, participants' hand movements were simultaneously attracted toward the unselected category response, indexing the degree to which such faces activated the opposite category in parallel. Multivoxel pattern analyses (MVPAs) provided evidence that such social category coactivation manifested in neural patterns of the right fusiform cortex. The extent to which the hand was simultaneously attracted to the opposite gender or race category response option corresponded to increased neural pattern similarity with the average pattern associated with that category, which in turn associated with stronger engagement of the dorsal anterior cingulate cortex. The findings point to a model of social categorization in which occasionally conflicting facial features are resolved through competition between coactivated ventral-temporal cortical representations with the assistance of conflict-monitoring regions. More broadly, the results offer a promising multimodal paradigm to investigate the neural basis of "hidden", temporarily active representations in the service of a broad range of cognitive processes. SIGNIFICANCE STATEMENT Individuals readily sort one another into social categories (e.g., sex, race), which have important consequences for a variety of interpersonal behaviors. However, individuals routinely encounter faces that contain diverse features associated with multiple categories (e.g., feminine male face). Using a novel paradigm combining neuroimaging with hand tracking, the present research sought to address how the brain comes to arrive at stable social categorizations from multiple social cues. The results provide evidence that opponent social categories coactivate in face-processing regions, which compete and may resolve into an eventual stable categorization with the assistance of conflict-monitoring regions. Therefore, the findings provide a neural mechanism through which the brain may translate inherently diverse social cues into coherent categorizations of other people. Copyright © 2017 the authors 0270-6474/17/375711-11$15.00/0.

Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

PubMed

Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

2018-02-01

Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

Attenuation of arsenic neurotoxicity by curcumin in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Rajesh S.; Sankhwar, Madhu Lata; Shukla, Rajendra K.

2009-11-01

In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associatedmore » with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.« less

Missouri University Multi-Plane Imager (MUMPI): A high sensitivity rapid dynamic ECT brain imager

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, K.W.; Holmes, R.A.

1984-01-01

The authors have designed a unique ECT imaging device that can record rapid dynamic images of brain perfusion. The Missouri University Multi-Plane Imager (MUMPI) uses a single crystal detector that produces four orthogonal two-dimensional images simultaneously. Multiple slice images are reconstructed from counts recorded from stepwise or continuous collimator rotation. Four simultaneous 2-d image fields may also be recorded and reviewed. The cylindrical sodium iodide crystal and the rotating collimator concentrically surround the source volume being imaged with the collimator the only moving part. The design and function parameters of MUMPI have been compared to other competitive tomographic head imagingmore » devices. MUMPI's principal advantages are: 1) simultaneous direct acquisition of four two-dimensional images; 2) extremely rapid project set acquisition for ECT reconstruction; and 3) instrument practicality and economy due to single detector design and the absence of heavy mechanical moving components (only collimator rotation is required). MUMPI should be ideal for imaging neutral lipophilic chelates such as Tc-99m-PnAO which passively diffuses across the intact blood-brain-barrier and rapidly clears from brain tissue.« less

Emotional Cues during Simultaneous Face and Voice Processing: Electrophysiological Insights

PubMed Central

Liu, Taosheng; Pinheiro, Ana; Zhao, Zhongxin; Nestor, Paul G.; McCarley, Robert W.; Niznikiewicz, Margaret A.

2012-01-01

Both facial expression and tone of voice represent key signals of emotional communication but their brain processing correlates remain unclear. Accordingly, we constructed a novel implicit emotion recognition task consisting of simultaneously presented human faces and voices with neutral, happy, and angry valence, within the context of recognizing monkey faces and voices task. To investigate the temporal unfolding of the processing of affective information from human face-voice pairings, we recorded event-related potentials (ERPs) to these audiovisual test stimuli in 18 normal healthy subjects; N100, P200, N250, P300 components were observed at electrodes in the frontal-central region, while P100, N170, P270 were observed at electrodes in the parietal-occipital region. Results indicated a significant audiovisual stimulus effect on the amplitudes and latencies of components in frontal-central (P200, P300, and N250) but not the parietal occipital region (P100, N170 and P270). Specifically, P200 and P300 amplitudes were more positive for emotional relative to neutral audiovisual stimuli, irrespective of valence, whereas N250 amplitude was more negative for neutral relative to emotional stimuli. No differentiation was observed between angry and happy conditions. The results suggest that the general effect of emotion on audiovisual processing can emerge as early as 200 msec (P200 peak latency) post stimulus onset, in spite of implicit affective processing task demands, and that such effect is mainly distributed in the frontal-central region. PMID:22383987

Scale-Free Brain-Wave Music from Simultaneously EEG and fMRI Recordings

PubMed Central

Lu, Jing; Wu, Dan; Yang, Hua; Luo, Cheng; Li, Chaoyi; Yao, Dezhong

2012-01-01

In the past years, a few methods have been developed to translate human EEG to music. In 2009, PloS One 4 e5915, we developed a method to generate scale-free brainwave music where the amplitude of EEG was translated to music pitch according to the power law followed by both of them, the period of an EEG waveform is translated directly to the duration of a note, and the logarithm of the average power change of EEG is translated to music intensity according to the Fechner's law. In this work, we proposed to adopt simultaneously-recorded fMRI signal to control the intensity of the EEG music, thus an EEG-fMRI music is generated by combining two different and simultaneous brain signals. And most importantly, this approach further realized power law for music intensity as fMRI signal follows it. Thus the EEG-fMRI music makes a step ahead in reflecting the physiological process of the scale-free brain. PMID:23166768

Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats.

PubMed

Dela Cruz, Julie A D; Coke, Tricia; Bodnar, Richard J

2016-08-24

This study uses cellular c-fos activation to assess effects of novel ingestion of fat and sugar on brain dopamine (DA) pathways in rats. Intakes of sugars and fats are mediated by their innate attractions as well as learned preferences. Brain dopamine, especially meso-limbic and meso-cortical projections from the ventral tegmental area (VTA), has been implicated in both of these unlearned and learned responses. The concept of distributed brain networks, wherein several sites and transmitter/peptide systems interact, has been proposed to mediate palatable food intake, but there is limited evidence empirically demonstrating such actions. Thus, sugar intake elicits DA release and increases c-fos-like immunoreactivity (FLI) from individual VTA DA projection zones including the nucleus accumbens (NAC), amygdala (AMY) and medial prefrontal cortex (mPFC) as well as the dorsal striatum. Further, central administration of selective DA receptor antagonists into these sites differentially reduce acquisition and expression of conditioned flavor preferences elicited by sugars or fats. One approach by which to determine whether these sites interacted as a distributed brain network in response to sugar or fat intake would be to simultaneous evaluate whether the VTA and its major mesotelencephalic DA projection zones (prelimbic and infralimbic mPFC, core and shell of the NAc, basolateral and central-cortico-medial AMY) as well as the dorsal striatum would display coordinated and simultaneous FLI activation after oral, unconditioned intake of corn oil (3.5%), glucose (8%), fructose (8%) and saccharin (0.2%) solutions. This approach is a successful first step in identifying the feasibility of using cellular c-fos activation simultaneously across relevant brain sites to study reward-related learning in ingestion of palatable food in rodents.

Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

PubMed

Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

2016-07-01

OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures.

Interpersonal brain synchronization in the right temporo-parietal junction during face-to-face economic exchange.

PubMed

Tang, Honghong; Mai, Xiaoqin; Wang, Shun; Zhu, Chaozhe; Krueger, Frank; Liu, Chao

2016-01-01

In daily life, interpersonal interactions are influenced by uncertainty about other people's intentions. Face-to-face (FF) interaction reduces such uncertainty by providing external visible cues such as facial expression or body gestures and facilitates shared intentionality to promote belief of cooperative decisions and actual cooperative behaviors in interaction. However, so far little is known about interpersonal brain synchronization between two people engaged in naturally occurring FF interactions. In this study, we combined an adapted ultimatum game with functional near-infrared spectroscopy (fNIRS) hyperscanning to investigate how FF interaction impacts interpersonal brain synchronization during economic exchange. Pairs of strangers interacted repeatedly either FF or face-blocked (FB), while their activation was simultaneously measured in the right temporo-parietal junction (rTPJ) and the control region, right dorsolateral prefrontal cortex (rDLPFC). Behaviorally, FF interactions increased shared intentionality between strangers, leading more positive belief of cooperative decisions and more actual gains in the game. FNIRS results indicated increased interpersonal brain synchronizations during FF interactions in rTPJ (but not in rDLPFC) with greater shared intentionality between partners. These results highlighted the importance of rTPJ in collaborative social interactions during FF economic exchange and warrant future research that combines FF interactions with fNIRS hyperscanning to study social brain disorders such as autism. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

PubMed Central

Zamberletti, Erica; Piscitelli, Fabiana; De Castro, Valentina; Murru, Elisabetta; Gabaglio, Marina; Colucci, Paola; Fanali, Chiara; Prini, Pamela; Bisogno, Tiziana; Maccarrone, Mauro; Campolongo, Patrizia; Banni, Sebastiano; Rubino, Tiziana; Parolaro, Daniela

2017-01-01

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition. PMID:27903595

Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury

PubMed Central

Genis, Laura; Dávila, David; Fernandez, Silvia; Pozo-Rodrigálvarez, Andrea; Martínez-Murillo, Ricardo; Torres-Aleman, Ignacio

2014-01-01

Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I) in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. We found that IGF-I directly protects astrocytes against oxidative stress (H 2O 2). Indeed, in astrocytes but not in neurons, IGF-I decreases the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H 2O 2 such as stem cell factor (SCF) to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging. PMID:24715976

Widespread Brain Areas Engaged during a Classical Auditory Streaming Task Revealed by Intracranial EEG

PubMed Central

Dykstra, Andrew R.; Halgren, Eric; Thesen, Thomas; Carlson, Chad E.; Doyle, Werner; Madsen, Joseph R.; Eskandar, Emad N.; Cash, Sydney S.

2011-01-01

The auditory system must constantly decompose the complex mixture of sound arriving at the ear into perceptually independent streams constituting accurate representations of individual sources in the acoustic environment. How the brain accomplishes this task is not well understood. The present study combined a classic behavioral paradigm with direct cortical recordings from neurosurgical patients with epilepsy in order to further describe the neural correlates of auditory streaming. Participants listened to sequences of pure tones alternating in frequency and indicated whether they heard one or two “streams.” The intracranial EEG was simultaneously recorded from sub-dural electrodes placed over temporal, frontal, and parietal cortex. Like healthy subjects, patients heard one stream when the frequency separation between tones was small and two when it was large. Robust evoked-potential correlates of frequency separation were observed over widespread brain areas. Waveform morphology was highly variable across individual electrode sites both within and across gross brain regions. Surprisingly, few evoked-potential correlates of perceptual organization were observed after controlling for physical stimulus differences. The results indicate that the cortical areas engaged during the streaming task are more complex and widespread than has been demonstrated by previous work, and that, by-and-large, correlates of bistability during streaming are probably located on a spatial scale not assessed – or in a brain area not examined – by the present study. PMID:21886615

[11C]Harmine Binding to Brain Monoamine Oxidase A: Test-Retest Properties and Noninvasive Quantification.

PubMed

Zanderigo, Francesca; D'Agostino, Alexandra E; Joshi, Nandita; Schain, Martin; Kumar, Dileep; Parsey, Ramin V; DeLorenzo, Christine; Mann, J John

2018-02-08

Inhibition of the isoform A of monoamine oxidase (MAO-A), a mitochondrial enzyme catalyzing deamination of monoamine neurotransmitters, is useful in treatment of depression and anxiety disorders. [ 11 C]harmine, a MAO-A PET radioligand, has been used to study mood disorders and antidepressant treatment. However, [ 11 C]harmine binding test-retest characteristics have to date only been partially investigated. Furthermore, since MAO-A is ubiquitously expressed, no reference region is available, thus requiring arterial blood sampling during PET scanning. Here, we investigate [ 11 C]harmine binding measurements test-retest properties; assess effects of using a minimally invasive input function estimation on binding quantification and repeatability; and explore binding potentials estimation using a reference region-free approach. Quantification of [ 11 C]harmine distribution volume (V T ) via kinetic models and graphical analyses was compared based on absolute test-retest percent difference (TRPD), intraclass correlation coefficient (ICC), and identifiability. The optimal procedure was also used with a simultaneously estimated input function in place of the measured curve. Lastly, an approach for binding potentials quantification in absence of a reference region was evaluated. [ 11 C]harmine V T estimates quantified using arterial blood and kinetic modeling showed average absolute TRPD values of 7.7 to 15.6 %, and ICC values between 0.56 and 0.86, across brain regions. Using simultaneous estimation (SIME) of input function resulted in V T estimates close to those obtained using arterial input function (r = 0.951, slope = 1.073, intercept = - 1.037), with numerically but not statistically higher test-retest difference (range 16.6 to 22.0 %), but with overall poor ICC values, between 0.30 and 0.57. Prospective studies using [ 11 C]harmine are possible given its test-retest repeatability when binding is quantified using arterial blood. Results with SIME of input function show potential for simplifying data acquisition by replacing arterial catheterization with one arterial blood sample at 20 min post-injection. Estimation of [ 11 C]harmine binding potentials remains a challenge that warrants further investigation.

Effects of an imprinting procedure on cell proliferation in the chick brain.

PubMed

Komissarova, N V; Anokhin, K V

2008-03-01

We report here studies on the effects of an imprinting procedure on cell proliferation in neonatal chicks in brain structures known to undergo plastic changes in imprinting. Proliferating cells were detected immunohistochemically on brain sections by incorporation of pre-training doses of 5-bromodeoxyuridine (BrdU) into DNA; numbers of new cells were counted in the intermediate medial mesopallium, the intermediate arcopallium, the medial part of the mesopallium and the nidopallium, the dorsocaudal nidopallium, the hippocampus, and the parahippocampal region 24 h and seven days after training. The intermediate medial mesopallium showed an increase in the number of BrdU-positive cells 24 h after training. However, at seven days post-training, the number of BrdU-containing cells decreased in the medial nidopallium and mesopallium, in the dorsocaudal nidopallium, and the right intermediate medial mesopallium. Thus, the imprinting procedure had differently directed transient and long-term influences on the genesis of new cells in the chick brain, inducing the appearance of a large number of cells in the parenchyma of the brain one day after training and decreases in the numbers of cells at later time points. This double effect may be associated with the fact that the imprinting procedure simultaneously initiates two brain processes involving the control of cell proliferation - one related to maturation of a species-specific functional system for tracking individuals of the same species and one related to remembering the characteristics of the actual parent.

Metabolomic Analysis in Brain Research: Opportunities and Challenges

PubMed Central

Vasilopoulou, Catherine G.; Margarity, Marigoula; Klapa, Maria I.

2016-01-01

Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s). Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results. PMID:27252656

Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain

NASA Astrophysics Data System (ADS)

Dziennis, Suzan; Qin, Jia; Shi, Lei; Wang, Ruikang K.

2015-05-01

The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

PubMed Central

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

[An automatic system for anatomophysiological correlation in three planes simultaneously during functional neurosurgery].

PubMed

Teijeiro, E J; Macías, R J; Morales, J M; Guerra, E; López, G; Alvarez, L M; Fernández, F; Maragoto, C; Seijo, F; Alvarez, E

The Neurosurgical Deep Recording System (NDRS) using a personal computer takes the place of complex electronic equipment for recording and processing deep cerebral electrical activity, as a guide in stereotaxic functional neurosurgery. It also permits increased possibilities of presenting information in direct graphic form with automatic management and sufficient flexibility to implement different analyses. This paper describes the possibilities of automatic simultaneous graphic representation in three almost orthogonal planes, available with the new 5.1 version of NDRS so as to facilitate the analysis of anatomophysiological correlation in the localization of deep structures of the brain during minimal access surgery. This new version can automatically show the spatial behaviour of signals registered throughout the path of the electrode inside the brain, superimposed simultaneously on sagittal, coronal and axial sections of an anatomical atlas of the brain, after adjusting the scale automatically according to the dimensions of the brain of each individual patient. This may also be shown in a tridimensional representation of the different planes themselves intercepting. The NDRS system has been successfully used in Spain and Cuba in over 300 functional neurosurgery operations. The new version further facilitates analysis of spatial anatomophysiological correlation for the localization of brain structures. This system has contributed to increase the precision and safety in selecting surgical targets in the control of Parkinson s disease and other disorders of movement.

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

PubMed Central

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

A Unified Estimation Framework for State-Related Changes in Effective Brain Connectivity.

PubMed

Samdin, S Balqis; Ting, Chee-Ming; Ombao, Hernando; Salleh, Sh-Hussain

2017-04-01

This paper addresses the critical problem of estimating time-evolving effective brain connectivity. Current approaches based on sliding window analysis or time-varying coefficient models do not simultaneously capture both slow and abrupt changes in causal interactions between different brain regions. To overcome these limitations, we develop a unified framework based on a switching vector autoregressive (SVAR) model. Here, the dynamic connectivity regimes are uniquely characterized by distinct vector autoregressive (VAR) processes and allowed to switch between quasi-stationary brain states. The state evolution and the associated directed dependencies are defined by a Markov process and the SVAR parameters. We develop a three-stage estimation algorithm for the SVAR model: 1) feature extraction using time-varying VAR (TV-VAR) coefficients, 2) preliminary regime identification via clustering of the TV-VAR coefficients, 3) refined regime segmentation by Kalman smoothing and parameter estimation via expectation-maximization algorithm under a state-space formulation, using initial estimates from the previous two stages. The proposed framework is adaptive to state-related changes and gives reliable estimates of effective connectivity. Simulation results show that our method provides accurate regime change-point detection and connectivity estimates. In real applications to brain signals, the approach was able to capture directed connectivity state changes in functional magnetic resonance imaging data linked with changes in stimulus conditions, and in epileptic electroencephalograms, differentiating ictal from nonictal periods. The proposed framework accurately identifies state-dependent changes in brain network and provides estimates of connectivity strength and directionality. The proposed approach is useful in neuroscience studies that investigate the dynamics of underlying brain states.

Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain

PubMed Central

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.

PubMed

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.

Cannabinoid modulation of zebrafish fear learning and its functional analysis investigated by c-Fos expression.

PubMed

Ruhl, Tim; Zeymer, Malou; von der Emde, Gerhard

2017-02-01

It has been shown that zebrafish fear learning proceeds in the same way as reported for rodents. However, in zebrafish fear learning it is possible to substitute the use of electric shocks as unconditioned stimulus and utilize the inborn fear responses to the alarm substance Schreckstoff, instead. The skin extract Schreckstoff elicits typical fear reactions such as preferred bottom dwelling, swimming in a tighter shoal, erratic movements and freezing. This natural fear behavior can be transferred from Schreckstoff to any other sensory stimulus by associative conditioning (fear learning). We presented Schreckstoff simultaneously with a red light stimulus and tested the effectiveness of fear learning during memory retrieval. The two brain regions known to be relevant for learning in zebrafish are the medial and the lateral pallium of the dorsal telencephalon, both containing rich expressions of the endocannabinoid receptor CB1. To test the influence of the zebrafish endocannabinoid system on fear acquisition learning, an experimental group of ten fish was pretreated with the CB1 receptor agonist THC (Δ 9 -tetrahydrocannabinol; 100nM for 1h). We found that CB1 activation significantly inhibited acquisition of fear learning, possibly by impairing stimulus encoding processes in pallial areas. This was supported by analyzes of c-Fos expression in the brains of experimental animals. Schreckstoff exposure during fear acquisition learning and memory retrieval during red light presentation increased the number of labelled cells in pallial structures, but in no other brain region investigated (e.g. striatum, thalamus, and habenula). THC administration before fear conditioning significantly decreased c-Fos expression in these structures to a level similar to the control group without Schreckstoff experience, suggesting that Schreckstoff induced fear learning requires brain circuits restricted mainly to pallial regions of the dorsal telencephalon. Copyright © 2016 Elsevier Inc. All rights reserved.

Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

PubMed

Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

2014-09-01

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

Characteristics analysis of acupuncture electroencephalograph based on mutual information Lempel—Ziv complexity

NASA Astrophysics Data System (ADS)

Luo, Xi-Liu; Wang, Jiang; Han, Chun-Xiao; Deng, Bin; Wei, Xi-Le; Bian, Hong-Rui

2012-02-01

As a convenient approach to the characterization of cerebral cortex electrical information, electroencephalograph (EEG) has potential clinical application in monitoring the acupuncture effects. In this paper, a method composed of the mutual information method and Lempel—Ziv complexity method (MILZC) is proposed to investigate the effects of acupuncture on the complexity of information exchanges between different brain regions based on EEGs. In the experiments, eight subjects are manually acupunctured at ‘Zusanli’ acupuncture point (ST-36) with different frequencies (i.e., 50, 100, 150, and 200 times/min) and the EEGs are recorded simultaneously. First, MILZC values are compared in general. Then average brain connections are used to quantify the effectiveness of acupuncture under the above four frequencies. Finally, significance index P values are used to study the spatiality of the acupuncture effect on the brain. Three main findings are obtained: (i) MILZC values increase during the acupuncture; (ii) manual acupunctures (MAs) with 100 times/min and 150 times/min are more effective than with 50 times/min and 200 times/min; (iii) contralateral hemisphere activation is more prominent than ipsilateral hemisphere's. All these findings suggest that acupuncture contributes to the increase of brain information exchange complexity and the MILZC method can successfully describe these changes.

Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter-speech sound learning in prereaders.

PubMed

Karipidis, Iliana I; Pleisch, Georgette; Brandeis, Daniel; Roth, Alexander; Röthlisberger, Martina; Schneebeli, Maya; Walitza, Susanne; Brem, Silvia

2018-05-08

During reading acquisition, neural reorganization of the human brain facilitates the integration of letters and speech sounds, which enables successful reading. Neuroimaging and behavioural studies have established that impaired audiovisual integration of letters and speech sounds is a core deficit in individuals with developmental dyslexia. This longitudinal study aimed to identify neural and behavioural markers of audiovisual integration that are related to future reading fluency. We simulated the first step of reading acquisition by performing artificial-letter training with prereading children at risk for dyslexia. Multiple logistic regressions revealed that our training provides new precursors of reading fluency at the beginning of reading acquisition. In addition, an event-related potential around 400 ms and functional magnetic resonance imaging activation patterns in the left planum temporale to audiovisual correspondences improved cross-validated prediction of future poor readers. Finally, an exploratory analysis combining simultaneously acquired electroencephalography and hemodynamic data suggested that modulation of temporoparietal brain regions depended on future reading skills. The multimodal approach demonstrates neural adaptations to audiovisual integration in the developing brain that are related to reading outcome. Despite potential limitations arising from the restricted sample size, our results may have promising implications both for identifying poor-reading children and for monitoring early interventions.

Neural correlates of pantomiming familiar and unfamiliar tools: action semantics versus mechanical problem solving?

PubMed

Vingerhoets, Guy; Vandekerckhove, Elisabeth; Honoré, Pieterjan; Vandemaele, Pieter; Achten, Eric

2011-06-01

This study aims to reveal the neural correlates of planning and executing tool use pantomimes and explores the brain's response to pantomiming the use of unfamiliar tools. Sixteen right-handed volunteers planned and executed pantomimes of equally graspable familiar and unfamiliar tools while undergoing fMRI. During the planning of these pantomimes, we found bilateral temporo-occipital and predominantly left hemispheric frontal and parietal activation. The execution of the pantomimes produced additional activation in frontal and sensorimotor regions. In the left posterior parietal region both familiar and unfamiliar tool pantomimes elicit peak activity in the anterior portion of the lateral bank of the intraparietal sulcus--A region associated with the representation of action goals. The cerebral activation during these pantomimes is remarkably similar for familiar and unfamiliar tools, and direct comparisons revealed only few differences. First, the left cuneus is significantly active during the planning of pantomimes of unfamiliar tools, reflecting increased visual processing of the novel objects. Second, executing (but not planning) familiar tool pantomimes showed significant activation on the convex portion of the inferior parietal lobule, a region believed to serve as a repository for skilled object-related gestures. Given the striking similarity in brain activation while pantomiming familiar and unfamiliar tools, we argue that normal subjects use both action semantics and function from structure inferences simultaneously and interactively to give rise to flexible object-to-goal directed behavior. Copyright © 2010 Wiley-Liss, Inc.

Neural control of vascular reactions: impact of emotion and attention.

PubMed

Okon-Singer, Hadas; Mehnert, Jan; Hoyer, Jana; Hellrung, Lydia; Schaare, Herma Lina; Dukart, Juergen; Villringer, Arno

2014-03-19

This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance.

A prototype MR insertable brain PET using tileable GAPD arrays.

PubMed

Hong, Key Jo; Choi, Yong; Jung, Jin Ho; Kang, Jihoon; Hu, Wei; Lim, Hyun Keong; Huh, Yoonsuk; Kim, Sangsu; Jung, Ji Woong; Kim, Kyu Bom; Song, Myung Sung; Park, Hyun-Wook

2013-04-01

The aim of this study was to develop a prototype magnetic resonance (MR)-compatible positron emission tomography (PET) that can be inserted into a MR imager and that allows simultaneous PET and MR imaging of the human brain. This paper reports the initial results of the authors' prototype brain PET system operating within a 3-T magnetic resonance imaging (MRI) system using newly developed Geiger-mode avalanche photodiode (GAPD)-based PET detectors, long flexible flat cables, position decoder circuit with high multiplexing ratio, and digital signal processing with field programmable gate array-based analog to digital converter boards. A brain PET with 72 detector modules arranged in a ring was constructed and mounted in a 3-T MRI. Each PET module was composed of cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled to a tileable GAPD. The GAPD output charge signals were transferred to preamplifiers using 3 m long flat cables. The LYSO and GAPD were located inside the MR bore and all electronics were positioned outside the MR bore. The PET detector performance was investigated both outside and inside the MRI, and MR image quality was evaluated with and without the PET system. The performance of the PET detector when operated inside the MRI during MR image acquisition showed no significant change in energy resolution and count rates, except for a slight degradation in timing resolution with an increase from 4.2 to 4.6 ns. Simultaneous PET/MR images of a hot-rod and Hoffman brain phantom were acquired in a 3-T MRI. Rods down to a diameter of 3.5 mm were resolved in the hot-rod PET image. The activity distribution patterns between the white and gray matter in the Hoffman brain phantom were well imaged. The hot-rod and Hoffman brain phantoms on the simultaneously acquired MR images obtained with standard sequences were observed without any noticeable artifacts, although MR image quality requires some improvement. These results demonstrate that the simultaneous acquisition of PET and MR images is feasible using the MR insertable PET developed in this study.

Brain science: from the very small to the very large.

PubMed

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.

Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") exposure.

PubMed

Coman, Daniel; Sanganahalli, Basavaraju G; Jiang, Lihong; Hyder, Fahmeed; Behar, Kevin L

2015-10-01

(+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an abused psychostimulant that produces strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP-3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA(4-))). The MDMA-induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA-induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.

Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA,‘ecstasy’) exposure

PubMed Central

Coman, Daniel; Sanganahalli, Basavaraju G.; Jiang, Lihong; Hyder, Fahmeed; Behar, Kevin L.

2015-01-01

(+/−)3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is an abused psychostimulant producing strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCP), primarily a type specific to skeletal muscle (UCP-3) and which is absent in brain, although other UCP types are expressed in brain (e.g., thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights of MDMA action, we measured spatial distributions of systemically-administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation of Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA4−)). The MDMA-induced temperature rise in cortex was greater than in subcortex (1.6±0.4°C vs. 1.3±0.4°C) and occurred more rapidly (2.0±0.2°C/h vs. 1.5±0.2°C/h). MDMA-induced temperature changes and dynamics in cortex and body were correlated, although body temperature exceeded cortex before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in cortex and subcortex (i.e., thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to cortex, a biphasic relationship was seen in subcortex (i.e., thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature >37°C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. PMID:26286889

Working memory load-dependent spatio-temporal activity of single-trial P3 response detected with an adaptive wavelet denoiser.

PubMed

Zhang, Qiushi; Yang, Xueqian; Yao, Li; Zhao, Xiaojie

2017-03-27

Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Simultaneous measurements of ascorbate and glutamate in vivo in the rat brain using carbon fiber nanocomposite sensors and microbiosensor arrays.

PubMed

Ferreira, Nuno R; Ledo, Ana; Laranjinha, João; Gerhardt, Greg A; Barbosa, Rui M

2018-06-01

Nanocomposite sensors consisting of carbon fiber microelectrodes modified with Nafion® and carbon nanotubes, and ceramic-based microelectrode biosensor arrays were used to measure ascorbate and glutamate in the brain with high spatial, temporal and chemical resolution. Nanocomposite sensors displayed electrocatalytic properties towards ascorbate oxidation, translated into a negative shift from +0.20V to -0.05V vs. Ag/AgCl, as well as a significant increase (10-fold) of electroactive surface area. The estimated average basal concentration of ascorbate in vivo in the CA1, CA3 and dentate gyrus (DG) sub regions of the hippocampus were 276±60μM (n=10), 183±30μM (n=10) and 133±42μM (n=10), respectively. The glutamate microbiosensor arrays showed a high sensitivity of 5.3±0.8pAμM -1 (n=18), and LOD of 204±32nM (n=10), and t 50% response time of 0.9±0.02s (n=6) and high selectivity against major interferents. The simultaneous and real-time measurements of glutamate and ascorbate in the hippocampus of anesthetized rats following local stimulus with KCl or glutamate revealed a dynamic interaction between the two neurochemicals. Copyright © 2018 Elsevier B.V. All rights reserved.

Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation.

PubMed

Wang, Dong V; Yau, Hau-Jie; Broker, Carl J; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi

2015-05-01

Sharp wave-associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.

Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation

PubMed Central

Wang, Dong V.; Yau, Hau-Jie; Broker, Carl J.; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi

2015-01-01

Sharp-wave associated field-oscillations (~200 Hz) of the hippocampus, referred to as “ripples”, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. Here we show that the median raphe region (MnR) plays a key role in regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus, and found that when a group of MnR neurons were active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity, while inhibition of these neurons increased ripple activity. Importantly, using a fear conditioning procedure, we provided evidence that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation. PMID:25867120

Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking Performance

PubMed Central

Vadas, Dor; Kalichman, Leonid; Hadanny, Amir; Efrati, Shai

2017-01-01

Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, <10% of the brain is active at any given time, it utilizes almost all the oxygen delivered. In order to perform complex tasks or more than one task (multitasking), the oxygen supply is shifted from one brain region to another, via blood perfusion modulation. The aim of the present study was to evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen supply to the brain, will enhance the performance of complex and/or multiple activities. Methods: A prospective, double-blind randomized control, crossover trial including 22 healthy volunteers. Participants were asked to perform a cognitive task, a motor task and a simultaneous cognitive-motor task (multitasking). Participants were randomized to perform the tasks in two environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen). Two weeks later participants were crossed to the alternative environment. Blinding of the normobaric environment was achieved in the same chamber with masks on while hyperbaric sensation was simulated by increasing pressure in the first minute and gradually decreasing to normobaric environment prior to tasks performance. Results: Compared to the performance at normobaric conditions, both cognitive and motor single tasks scores were significantly enhanced by HBO environment (p < 0.001 for both). Multitasking performance was also significantly enhanced in HBO environment (p = 0.006 for the cognitive part and p = 0.02 for the motor part). Conclusions: The improvement in performance of both single and multi-tasking while in an HBO environment supports the hypothesis which according to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric oxygenation can serve as an environment for brain performance. Further studies are needed to evaluate the optimal oxygen levels for maximal brain performance. PMID:29021747

Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking Performance.

PubMed

Vadas, Dor; Kalichman, Leonid; Hadanny, Amir; Efrati, Shai

2017-01-01

Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, <10% of the brain is active at any given time, it utilizes almost all the oxygen delivered. In order to perform complex tasks or more than one task (multitasking), the oxygen supply is shifted from one brain region to another, via blood perfusion modulation. The aim of the present study was to evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen supply to the brain, will enhance the performance of complex and/or multiple activities. Methods: A prospective, double-blind randomized control, crossover trial including 22 healthy volunteers. Participants were asked to perform a cognitive task, a motor task and a simultaneous cognitive-motor task (multitasking). Participants were randomized to perform the tasks in two environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen). Two weeks later participants were crossed to the alternative environment. Blinding of the normobaric environment was achieved in the same chamber with masks on while hyperbaric sensation was simulated by increasing pressure in the first minute and gradually decreasing to normobaric environment prior to tasks performance. Results: Compared to the performance at normobaric conditions, both cognitive and motor single tasks scores were significantly enhanced by HBO environment ( p < 0.001 for both). Multitasking performance was also significantly enhanced in HBO environment ( p = 0.006 for the cognitive part and p = 0.02 for the motor part). Conclusions: The improvement in performance of both single and multi-tasking while in an HBO environment supports the hypothesis which according to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric oxygenation can serve as an environment for brain performance. Further studies are needed to evaluate the optimal oxygen levels for maximal brain performance.

Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands.

PubMed

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

PubMed Central

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

Rapid simultaneous high-resolution mapping of myelin water fraction and relaxation times in human brain using BMC-mcDESPOT.

PubMed

Bouhrara, Mustapha; Spencer, Richard G

2017-02-15

A number of central nervous system (CNS) diseases exhibit changes in myelin content and magnetic resonance longitudinal, T 1 , and transverse, T 2 , relaxation times, which therefore represent important biomarkers of CNS pathology. Among the methods applied for measurement of myelin water fraction (MWF) and relaxation times, the multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT) approach is of particular interest. mcDESPOT permits whole brain mapping of multicomponent T 1 and T 2 , with data acquisition accomplished within a clinically realistic acquisition time. Unfortunately, previous studies have indicated the limited performance of mcDESPOT in the setting of the modest signal-to-noise range of high-resolution mapping, required for the depiction of small structures and to reduce partial volume effects. Recently, we showed that a new Bayesian Monte Carlo (BMC) analysis substantially improved determination of MWF from mcDESPOT imaging data. However, our previous study was limited in that it did not discuss determination of relaxation times. Here, we extend the BMC analysis to the simultaneous determination of whole-brain MWF and relaxation times using the two-component mcDESPOT signal model. Simulation analyses and in-vivo human brain studies indicate the overall greater performance of this approach compared to the stochastic region contraction (SRC) algorithm, conventionally used to derive parameter estimates from mcDESPOT data. SRC estimates of the transverse relaxation time of the long T 2 fraction, T 2,l , and the longitudinal relaxation time of the short T 1 fraction, T 1,s , clustered towards the lower and upper parameter search space limits, respectively, indicating failure of the fitting procedure. We demonstrate that this effect is absent in the BMC analysis. Our results also showed improved parameter estimation for BMC as compared to SRC for high-resolution mapping. Overall we find that the combination of BMC analysis and mcDESPOT, BMC-mcDESPOT, shows excellent performance for accurate high-resolution whole-brain mapping of MWF and bi-component transverse and longitudinal relaxation times within a clinically realistic acquisition time. Published by Elsevier Inc.

One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease.

PubMed

Coenen, Volker Arnd; Rijntjes, Michel; Prokop, Thomas; Piroth, Tobias; Amtage, Florian; Urbach, Horst; Reinacher, Peter Christoph

2016-04-01

Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. Both patients showed immediate and sustained improvement of their tremor, bilaterally. The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research.

Simultaneous total cavopulmonary connection and cardiac re-synchronisation therapy.

PubMed

Nakanishi, Keisuke; Kawasaki, Shiori; Amano, Atsushi

2017-08-01

We report the simultaneous use of cardiac re-synchronisation therapy and total cavopulmonary connection in a patient with dyssynchrony, wide QRS, and cardiac failure. To our knowledge, this simultaneous approach has not been reported previously. On follow-up, we noted that QRS width and brain natriuretic peptide levels improved. In addition, speckle tracking revealed improved synchronisation of ventricular wall motion.

Rates of Cerebral Protein Synthesis in Primary Visual Cortex during Sleep-Dependent Memory Consolidation, a Study in Human Subjects.

PubMed

Picchioni, Dante; Schmidt, Kathleen C; McWhirter, Kelly K; Loutaev, Inna; Pavletic, Adriana J; Speer, Andrew M; Zametkin, Alan J; Miao, Ning; Bishu, Shrinivas; Turetsky, Kate M; Morrow, Anne S; Nadel, Jeffrey L; Evans, Brittney C; Vesselinovitch, Diana M; Sheeler, Carrie A; Balkin, Thomas J; Smith, Carolyn B

2018-05-15

If protein synthesis during sleep is required for sleep-dependent memory consolidation, we might expect rates of cerebral protein synthesis (rCPS) to increase during sleep in the local brain circuits that support performance on a particular task following training on that task. To measure circuit-specific brain protein synthesis during a daytime nap opportunity, we used the L-[1-(11)C]leucine positron emission tomography (PET) method with simultaneous polysomnography. We trained subjects on the visual texture discrimination task (TDT). This was followed by a nap opportunity during the PET scan, and we retested them later in the day after the scan. The TDT is considered retinotopically specific, so we hypothesized that higher rCPS in primary visual cortex would be observed in the trained hemisphere compared to the untrained hemisphere in subjects who were randomized to a sleep condition. Our results indicate that the changes in rCPS in primary visual cortex depended on whether subjects were in the wakefulness or sleep condition but were independent of the side of the visual field trained. That is, only in the subjects randomized to sleep, rCPS in the right primary visual cortex was higher than the left regardless of side trained. Other brain regions examined were not so affected. In the subjects who slept, performance on the TDT improved similarly regardless of the side trained. Results indicate a regionally selective and sleep-dependent effect that occurs with improved performance on the TDT.

Stable Microsaccades and Microsaccade-Induced Global Alpha Band Phase Reset Across the Life Span.

PubMed

Gao, Ying; Huber, Carl; Sabel, Bernhard A

2018-04-01

To understand the effect of aging on microsaccade functions and brain physiologic responses, we quantified microsaccades and their physiologic correlates (including their interaction with alpha band brain oscillation) in normal subjects of different ages. Twenty-two normally sighted young (18 to 29 years), 22 middle-aged (31 to 55 years), and 22 elderly subjects (56 to 77 years) participated in this cross-sectional study. Dense array EEG and high-resolution eye-tracking data were simultaneously recorded during a fixation task. We quantified microsaccade features, spike potential (SP), microsaccadic lambda response (MLR) and microsaccade-related spectral perturbation (ERSP), and intertrial coherence (ITC) in the alpha and beta frequency bands and compared them between three age groups. After microsaccade onset, (1) alpha band ERSP increased (100 to 150 ms) occipitally and ITC increased (150 to 220 ms) globally in the brain; (2) low beta ITC increased (150 to 220 ms) in occipital and central regions and peaked (0 to 50 ms) in frontal region; and (3) high beta ITC increased (0 to 50 ms) globally with no beta band ERSP changes. Microsaccade features, the latency and amplitude of SP and MLR, and microsaccade-related temporal-spectral power and synchronization dynamics were all stable across different age groups. Microsaccades are well preserved in aging and can be used as reference points for studying neurodegenerative or neuro-ophthalmologic diseases where the oculomotor system is affected. Microsaccade-induced alpha band activity is a potential biomarker to better understand and monitor these diseases, and we propose that microsaccades trigger "cortical refreshment" by resetting alpha band phase globally to prepare (sensitize) the brain for subsequent visual processing.

From brain topography to brain topology: relevance of graph theory to functional neuroscience.

PubMed

Minati, Ludovico; Varotto, Giulia; D'Incerti, Ludovico; Panzica, Ferruccio; Chan, Dennis

2013-07-10

Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians.

Simultaneous neuron- and astrocyte-specific fluorescent marking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, Wiebke; Hayata-Takano, Atsuko; Kamo, Toshihiko

2015-03-27

Systematic and simultaneous analysis of multiple cell types in the brain is becoming important, but such tools have not yet been adequately developed. Here, we aimed to generate a method for the specific fluorescent labeling of neurons and astrocytes, two major cell types in the brain, and we have developed lentiviral vectors to express the red fluorescent protein tdTomato in neurons and the enhanced green fluorescent protein (EGFP) in astrocytes. Importantly, both fluorescent proteins are fused to histone 2B protein (H2B) to confer nuclear localization to distinguish between single cells. We also constructed several expression constructs, including a tandem alignmentmore » of the neuron- and astrocyte-expression cassettes for simultaneous labeling. Introducing these vectors and constructs in vitro and in vivo resulted in cell type-specific and nuclear-localized fluorescence signals enabling easy detection and distinguishability of neurons and astrocytes. This tool is expected to be utilized for the simultaneous analysis of changes in neurons and astrocytes in healthy and diseased brains. - Highlights: • We develop a method for the specific fluorescent labeling of neurons and astrocytes. • Neuron-specific labeling is achieved using Scg10 and synapsin promoters. • Astrocyte-specific labeling is generated using the minimal GFAP promoter. • Nuclear localization of fluorescent proteins is achieved with histone 2B protein.« less

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Extendable supervised dictionary learning for exploring diverse and concurrent brain activities in task-based fMRI.

PubMed

Zhao, Shijie; Han, Junwei; Hu, Xintao; Jiang, Xi; Lv, Jinglei; Zhang, Tuo; Zhang, Shu; Guo, Lei; Liu, Tianming

2018-06-01

Recently, a growing body of studies have demonstrated the simultaneous existence of diverse brain activities, e.g., task-evoked dominant response activities, delayed response activities and intrinsic brain activities, under specific task conditions. However, current dominant task-based functional magnetic resonance imaging (tfMRI) analysis approach, i.e., the general linear model (GLM), might have difficulty in discovering those diverse and concurrent brain responses sufficiently. This subtraction-based model-driven approach focuses on the brain activities evoked directly from the task paradigm, thus likely overlooks other possible concurrent brain activities evoked during the information processing. To deal with this problem, in this paper, we propose a novel hybrid framework, called extendable supervised dictionary learning (E-SDL), to explore diverse and concurrent brain activities under task conditions. A critical difference between E-SDL framework and previous methods is that we systematically extend the basic task paradigm regressor into meaningful regressor groups to account for possible regressor variation during the information processing procedure in the brain. Applications of the proposed framework on five independent and publicly available tfMRI datasets from human connectome project (HCP) simultaneously revealed more meaningful group-wise consistent task-evoked networks and common intrinsic connectivity networks (ICNs). These results demonstrate the advantage of the proposed framework in identifying the diversity of concurrent brain activities in tfMRI datasets.

Scatter and cross-talk corrections in simultaneous Tc-99m/I-123 brain SPECT using constrained factor analysis and artificial neural networks

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Maksud, P.; Kijewski, M. F.; Haberi, M. O.; Todd-Pokropek, A.; Aurengo, A.; Moore, S. C.

2000-08-01

Simultaneous imaging of Tc-99m and I-123 would have a high clinical potential in the assessment of brain perfusion (Tc-99m) and neurotransmission (I-123) but is hindered by cross-talk between the two radionuclides. Monte Carlo simulations of 15 different dual-isotope studies were performed using a digital brain phantom. Several physiologic Tc-99m and I-123 uptake patterns were modeled in the brain structures. Two methods were considered to correct for cross-talk from both scattered and unscattered photons: constrained spectral factor analysis (SFA) and artificial neural networks (ANN). The accuracy and precision of reconstructed pixel values within several brain structures were compared to those obtained with an energy windowing method (WSA). In I-123 images, mean bias was close to 10% in all structures for SFA and ANN and between 14% (in the caudate nucleus) and 25% (in the cerebellum) for WSA. Tc-99m activity was overestimated by 35% in the cortex and 53% in the caudate nucleus with WSA, but by less than 9% in all structures with SFA and ANN. SFA and ANN performed well even in the presence of high-energy I-123 photons. The accuracy was greatly improved by incorporating the contamination into the SFA model or in the learning phase for ANN. SFA and ANN are promising approaches to correct for cross-talk in simultaneous Tc-99m/I-123 SPECT.

[Associative Learning between Orientation and Color in Early Visual Areas].

PubMed

Amano, Kaoru; Shibata, Kazuhisa; Kawato, Mitsuo; Sasaki, Yuka; Watanabe, Takeo

2017-08-01

Associative learning is an essential neural phenomenon where the contingency of different items increases after training. Although associative learning has been found to occur in many brain regions, there is no clear evidence that associative learning of visual features occurs in early visual areas. Here, we developed an associative decoded functional magnetic resonance imaging (fMRI) neurofeedback (A-DecNef) to determine whether associative learning of color and orientation can be induced in early visual areas. During the three days' training, A-DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was simultaneously, physically presented to participants. Consequently, participants' perception of "red" was significantly more frequently than that of "green" in an achromatic vertical grating. This effect was also observed 3 to 5 months after training. These results suggest that long-term associative learning of two different visual features such as color and orientation, was induced most likely in early visual areas. This newly extended technique that induces associative learning may be used as an important tool for understanding and modifying brain function, since associations are fundamental and ubiquitous with respect to brain function.

Action Categorization in Rhesus Monkeys: discrimination of grasping from non-grasping manual motor acts.

PubMed

Nelissen, Koen; Vanduffel, Wim

2017-11-08

The ability to recognize others' actions is an important aspect of social behavior. While neurophysiological and behavioral research in monkeys has offered a better understanding of how the primate brain processes this type of information, further insight with respect to the neural correlates of action recognition requires tasks that allow recording of brain activity or perturbing brain regions while monkeys simultaneously make behavioral judgements about certain aspects of observed actions. Here we investigated whether rhesus monkeys could actively discriminate videos showing grasping or non-grasping manual motor acts in a two-alternative categorization task. After monkeys became proficient in this task, we tested their ability to generalize to a number of untrained, novel videos depicting grasps or other manual motor acts. Monkeys generalized to a wide range of novel human or conspecific grasping and non-grasping motor acts. They failed, however, for videos showing unfamiliar actions such as a non-biological effector performing a grasp, or a human hand touching an object with the back of the hand. This study shows the feasibility of training monkeys to perform active judgements about certain aspects of observed actions, instrumental for causal investigations into the neural correlates of action recognition.

CNS angiogenesis and barriergenesis occur simultaneously.

PubMed

Umans, Robyn A; Henson, Hannah E; Mu, Fangzhou; Parupalli, Chaithanyarani; Ju, Bensheng; Peters, Jennifer L; Lanham, Kevin A; Plavicki, Jessica S; Taylor, Michael R

2017-05-15

The blood-brain barrier (BBB) plays a vital role in the central nervous system (CNS). A comprehensive understanding of BBB development has been hampered by difficulties in observing the differentiation of brain endothelial cells (BECs) in real-time. Here, we generated two transgenic zebrafish line, Tg(glut1b:mCherry) and Tg(plvap:EGFP), to serve as in vivo reporters of BBB development. We showed that barriergenesis (i.e. the induction of BEC differentiation) occurs immediately as endothelial tips cells migrate into the brain parenchyma. Using the Tg(glut1b:mCherry) transgenic line, we performed a genetic screen and identified a zebrafish mutant with a nonsense mutation in gpr124, a gene known to play a role in CNS angiogenesis and BBB development. We also showed that our transgenic plvap:EGFP line, a reporter of immature brain endothelium, is initially expressed in newly formed brain endothelial cells, but subsides during BBB maturation. Our results demonstrate the ability to visualize the in vivo differentiation of brain endothelial cells into the BBB phenotype and establish that CNS angiogenesis and barriergenesis occur simultaneously. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Fitted hyperelastic parameters for Human brain tissue from reported tension, compression, and shear tests.

PubMed

Moran, Richard; Smith, Joshua H; García, José J

2014-11-28

The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795-2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897-1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of regional brain mitochondrial bioenergetics and susceptibility to mitochondrial inhibition utilizing a microplate based system

PubMed Central

Sauerbeck, Andrew; Pandya, Jignesh; Singh, Indrapal; Bittman, Kevin; Readnower, Ryan; Bing, Guoying; Sullivan, Patrick

2012-01-01

The analysis of mitochondrial bioenergetic function typically has required 50–100 μg of protein per sample and at least 15 min per run when utilizing a Clark-type oxygen electrode. In the present work we describe a method utilizing the Seahorse Biosciences XF24 Flux Analyzer for measuring mitochondrial oxygen consumption simultaneously from multiple samples and utilizing only 5 μg of protein per sample. Utilizing this method we have investigated whether regionally based differences exist in mitochondria isolated from the cortex, striatum, hippocampus, and cerebellum. Analysis of basal mitochondrial bioenergetics revealed that minimal differences exist between the cortex, striatum, and hippocampus. However, the cerebellum exhibited significantly slower basal rates of Complex I and Complex II dependent oxygen consumption (p < 0.05). Mitochondrial inhibitors affected enzyme activity proportionally across all samples tested and only small differences existed in the effect of inhibitors on oxygen consumption. Investigation of the effect of rotenone administration on Complex I dependent oxygen consumption revealed that exposure to 10 pM rotenone led to a clear time dependent decrease in oxygen consumption beginning 12 min after administration (p < 0.05). These studies show that the utilization of this microplate based method for analysis of mitochondrial bioenergetics is effective at quantifying oxygen consumption simultaneously from multiple samples. Additionally, these studies indicate that minimal regional differences exist in mitochondria isolated from the cortex, striatum, or hippocampus. Furthermore, utilization of the mitochondrial inhibitors suggests that previous work indicating regionally specific deficits following systemic mitochondrial toxin exposure may not be the result of differences in the individual mitochondria from the affected regions. PMID:21402103

Simultaneous detection of Zika, Chikungunya and Dengue viruses by a multiplex real-time RT-PCR assay.

PubMed

Pabbaraju, Kanti; Wong, Sallene; Gill, Kara; Fonseca, Kevin; Tipples, Graham A; Tellier, Raymond

2016-10-01

In the recent past, arboviruses such as Chikungunya (CHIKV) and Zika (ZIKV) have increased their area of endemicity and presented as an emerging global public health threat. To design an assay for the simultaneous detection of ZIKV, CHIKV and Dengue (DENV) 1-4 from patients with symptoms of arboviral infection. This would be advantageous because of the similar clinical presentation typically encountered with these viruses and their co-circulation in endemic areas. In this study we have developed and validated a triplex real time reverse transcription PCR assay using hydrolysis probes targeting the non-structural 5 (NS5) region of ZIKV, non-structural protein 4 (nsP4) from CHIKV and 3' untranslated region (3'UTR) of DENV 1-4. The 95% LOD by the triplex assay was 15 copies/reaction for DENV-1 and less than 10 copies/reaction for all other viruses. The triplex assay was 100% specific and did not amplify any of the other viruses tested. The assay was reproducible and adaptable to testing different specimen types including serum, plasma, urine, placental tissue, brain tissue and amniotic fluid. This assay can be easily implemented for diagnostic testing of patient samples, even in a high throughput laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

Combining EEG, MIDI, and motion capture techniques for investigating musical performance.

PubMed

Maidhof, Clemens; Kästner, Torsten; Makkonen, Tommi

2014-03-01

This article describes a setup for the simultaneous recording of electrophysiological data (EEG), musical data (MIDI), and three-dimensional movement data. Previously, each of these three different kinds of measurements, conducted sequentially, has been proven to provide important information about different aspects of music performance as an example of a demanding multisensory motor skill. With the method described here, it is possible to record brain-related activity and movement data simultaneously, with accurate timing resolution and at relatively low costs. EEG and MIDI data were synchronized with a modified version of the FTAP software, sending synchronization signals to the EEG recording device simultaneously with keypress events. Similarly, a motion capture system sent synchronization signals simultaneously with each recorded frame. The setup can be used for studies investigating cognitive and motor processes during music performance and music-like tasks--for example, in the domains of motor control, learning, music therapy, or musical emotions. Thus, this setup offers a promising possibility of a more behaviorally driven analysis of brain activity.

Selective entrainment of brain oscillations drives auditory perceptual organization.

PubMed

Costa-Faidella, Jordi; Sussman, Elyse S; Escera, Carles

2017-10-01

Perceptual sound organization supports our ability to make sense of the complex acoustic environment, to understand speech and to enjoy music. However, the neuronal mechanisms underlying the subjective experience of perceiving univocal auditory patterns that can be listened to, despite hearing all sounds in a scene, are poorly understood. We hereby investigated the manner in which competing sound organizations are simultaneously represented by specific brain activity patterns and the way attention and task demands prime the internal model generating the current percept. Using a selective attention task on ambiguous auditory stimulation coupled with EEG recordings, we found that the phase of low-frequency oscillatory activity dynamically tracks multiple sound organizations concurrently. However, whereas the representation of ignored sound patterns is circumscribed to auditory regions, large-scale oscillatory entrainment in auditory, sensory-motor and executive-control network areas reflects the active perceptual organization, thereby giving rise to the subjective experience of a unitary percept. Copyright © 2017 Elsevier Inc. All rights reserved.

Degraded perceptual and affective processing of racial out-groups: An electrophysiological approach.

PubMed

Sheng, Feng; Du, Na; Han, Shihui

2017-08-01

Human beings process perceptual and affective information of racial out-groups in a degraded manner. Relative to racial in-group members, we lack perceptual individuation of racial out-group members and empathize their pain to a less degree. To date, however, the relationship between the deficiency of individuation and the impairment of empathy in responding to racial out-groups remains elusive. By recording event-related brain potentials in response to racial in-group and out-group faces portraying pain and neutral expressions, we simultaneously measured neural activity that underpinned individuation and empathy. Deficiency in individuating members of racial out-groups, manifesting as reduced reactivity of face-sensitive N170 in the occipitotemporal region of the brain, predicted attenuation of fronto-central empathic response to the suffering of racial out-groups. Further, the individuation bias mediated the influence of racial prejudice on racial in-group bias in empathic neural responses. These findings suggest an interplay between degraded perceptual and affective processing of racial out-groups.

Modeling Alzheimer's disease cognitive scores using multi-task sparse group lasso.

PubMed

Liu, Xiaoli; Goncalves, André R; Cao, Peng; Zhao, Dazhe; Banerjee, Arindam

2018-06-01

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by loss of memory and reduction in cognitive functions due to progressive degeneration of neurons and their connections, eventually leading to death. In this paper, we consider the problem of simultaneously predicting several different cognitive scores associated with categorizing subjects as normal, mild cognitive impairment (MCI), or Alzheimer's disease (AD) in a multi-task learning framework using features extracted from brain images obtained from ADNI (Alzheimer's Disease Neuroimaging Initiative). To solve the problem, we present a multi-task sparse group lasso (MT-SGL) framework, which estimates sparse features coupled across tasks, and can work with loss functions associated with any Generalized Linear Models. Through comparisons with a variety of baseline models using multiple evaluation metrics, we illustrate the promising predictive performance of MT-SGL on ADNI along with its ability to identify brain regions more likely to help the characterization Alzheimer's disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

EEG based topography analysis in string recognition task

NASA Astrophysics Data System (ADS)

Ma, Xiaofei; Huang, Xiaolin; Shen, Yuxiaotong; Qin, Zike; Ge, Yun; Chen, Ying; Ning, Xinbao

2017-03-01

Vision perception and recognition is a complex process, during which different parts of brain are involved depending on the specific modality of the vision target, e.g. face, character, or word. In this study, brain activities in string recognition task compared with idle control state are analyzed through topographies based on multiple measurements, i.e. sample entropy, symbolic sample entropy and normalized rhythm power, extracted from simultaneously collected scalp EEG. Our analyses show that, for most subjects, both symbolic sample entropy and normalized gamma power in string recognition task are significantly higher than those in idle state, especially at locations of P4, O2, T6 and C4. It implies that these regions are highly involved in string recognition task. Since symbolic sample entropy measures complexity, from the perspective of new information generation, and normalized rhythm power reveals the power distributions in frequency domain, complementary information about the underlying dynamics can be provided through the two types of indices.

Increased photon emission from the head while imagining light in the dark is correlated with changes in electroencephalographic power: support for Bókkon's biophoton hypothesis.

PubMed

Dotta, B T; Saroka, K S; Persinger, M A

2012-04-04

Bókkon's hypothesis that photons released from chemical processes within the brain produce biophysical pictures during visual imagery has been supported experimentally. In the present study measurements by a photomultiplier tube also demonstrated significant increases in ultraweak photon emissions (UPEs) or biophotons equivalent to about 5×10(-11)W/m(2) from the right sides of volunteer's heads when they imagined light in a very dark environment compared to when they did not. Simultaneous variations in regional quantitative electroencephalographic spectral power (μV(2)/Hz) and total energy in the range of ∼10(-12)J from concurrent biophoton emissions were strongly correlated (r=0.95). The calculated energy was equivalent to that associated with action potentials from about 10(7) cerebral cortical neurons. We suggest these results support Bókkon's hypothesis that specific visual imagery is strongly correlated with ultraweak photon emission coupled to brain activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Two spatiotemporally distinct value systems shape reward-based learning in the human brain.

PubMed

Fouragnan, Elsa; Retzler, Chris; Mullinger, Karen; Philiastides, Marios G

2015-09-08

Avoiding repeated mistakes and learning to reinforce rewarding decisions is critical for human survival and adaptive actions. Yet, the neural underpinnings of the value systems that encode different decision-outcomes remain elusive. Here coupling single-trial electroencephalography with simultaneously acquired functional magnetic resonance imaging, we uncover the spatiotemporal dynamics of two separate but interacting value systems encoding decision-outcomes. Consistent with a role in regulating alertness and switching behaviours, an early system is activated only by negative outcomes and engages arousal-related and motor-preparatory brain structures. Consistent with a role in reward-based learning, a later system differentially suppresses or activates regions of the human reward network in response to negative and positive outcomes, respectively. Following negative outcomes, the early system interacts and downregulates the late system, through a thalamic interaction with the ventral striatum. Critically, the strength of this coupling predicts participants' switching behaviour and avoidance learning, directly implicating the thalamostriatal pathway in reward-based learning.

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

PubMed

Cecchin, Diego; Palombit, Alessandro; Castellaro, Marco; Silvestri, Erica; Bui, Franco; Barthel, Henryk; Sabri, Osama; Corbetta, Maurizio; Bertoldo, Alessandra

2017-12-01

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system.

PubMed

Zamberletti, Erica; Piscitelli, Fabiana; De Castro, Valentina; Murru, Elisabetta; Gabaglio, Marina; Colucci, Paola; Fanali, Chiara; Prini, Pamela; Bisogno, Tiziana; Maccarrone, Mauro; Campolongo, Patrizia; Banni, Sebastiano; Rubino, Tiziana; Parolaro, Daniela

2017-02-01

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Resolving Structural Variability in Network Models and the Brain

PubMed Central

Klimm, Florian; Bassett, Danielle S.; Carlson, Jean M.; Mucha, Peter J.

2014-01-01

Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling—in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data. PMID:24675546

Scales

ScienceCinema

Murray Gibson

2017-12-09

Musical scales involve notes that, sounded simultaneously (chords), sound good together. The result is the left brain meeting the right brain — a Pythagorean interval of overlapping notes. This synergy would suggest less difference between the working of the right brain and the left brain than common wisdom would dictate. The pleasing sound of harmony comes when two notes share a common harmonic, meaning that their frequencies are in simple integer ratios, such as 3/2 (G/C) or 5/4 (E/C).

An Evolutionary Computation Approach to Examine Functional Brain Plasticity.

PubMed

Roy, Arnab; Campbell, Colin; Bernier, Rachel A; Hillary, Frank G

2016-01-01

One common research goal in systems neurosciences is to understand how the functional relationship between a pair of regions of interest (ROIs) evolves over time. Examining neural connectivity in this way is well-suited for the study of developmental processes, learning, and even in recovery or treatment designs in response to injury. For most fMRI based studies, the strength of the functional relationship between two ROIs is defined as the correlation between the average signal representing each region. The drawback to this approach is that much information is lost due to averaging heterogeneous voxels, and therefore, the functional relationship between a ROI-pair that evolve at a spatial scale much finer than the ROIs remain undetected. To address this shortcoming, we introduce a novel evolutionary computation (EC) based voxel-level procedure to examine functional plasticity between an investigator defined ROI-pair by simultaneously using subject-specific BOLD-fMRI data collected from two sessions seperated by finite duration of time. This data-driven procedure detects a sub-region composed of spatially connected voxels from each ROI (a so-called sub-regional-pair) such that the pair shows a significant gain/loss of functional relationship strength across the two time points. The procedure is recursive and iteratively finds all statistically significant sub-regional-pairs within the ROIs. Using this approach, we examine functional plasticity between the default mode network (DMN) and the executive control network (ECN) during recovery from traumatic brain injury (TBI); the study includes 14 TBI and 12 healthy control subjects. We demonstrate that the EC based procedure is able to detect functional plasticity where a traditional averaging based approach fails. The subject-specific plasticity estimates obtained using the EC-procedure are highly consistent across multiple runs. Group-level analyses using these plasticity estimates showed an increase in the strength of functional relationship between DMN and ECN for TBI subjects, which is consistent with prior findings in the TBI-literature. The EC-approach also allowed us to separate sub-regional-pairs contributing to positive and negative plasticity; the detected sub-regional-pairs significantly overlap across runs thus highlighting the reliability of the EC-approach. These sub-regional-pairs may be useful in performing nuanced analyses of brain-behavior relationships during recovery from TBI.

Simultaneous recording of eeg and direct current (DC) potential makes it possible to assess functional and metabolic state of nervous tissue.

PubMed

Murik, S E; Shapkin, A G

2004-08-01

It has been proposed to assess functional and metabolic state of the brain nervous tissue in terms of bioelectrical parameters. Simultaneous recording of the DC potential level and total slow electrical activity of the nervous tissue was performed in the object of study by nonpolarizable Ag/AgCl electrodes with a DC amplifier. The functional and metabolic state of the brain was determined in terms of enhancement or reduction in the total slow electrical activity and positive or negative shifts in the DC potential level.

Brain size and visual environment predict species differences in paper wasp sensory processing brain regions (hymenoptera: vespidae, polistinae).

PubMed

O'Donnell, Sean; Clifford, Marie R; DeLeon, Sara; Papa, Christopher; Zahedi, Nazaneen; Bulova, Susan J

2013-01-01

The mosaic brain evolution hypothesis predicts that the relative volumes of functionally distinct brain regions will vary independently and correlate with species' ecology. Paper wasp species (Hymenoptera: Vespidae, Polistinae) differ in light exposure: they construct open versus enclosed nests and one genus (Apoica) is nocturnal. We asked whether light environments were related to species differences in the size of antennal and optic processing brain tissues. Paper wasp brains have anatomically distinct peripheral and central regions that process antennal and optic sensory inputs. We measured the volumes of 4 sensory processing brain regions in paper wasp species from 13 Neotropical genera including open and enclosed nesters, and diurnal and nocturnal species. Species differed in sensory region volumes, but there was no evidence for trade-offs among sensory modalities. All sensory region volumes correlated with brain size. However, peripheral optic processing investment increased with brain size at a higher rate than peripheral antennal processing investment. Our data suggest that mosaic and concerted (size-constrained) brain evolution are not exclusive alternatives. When brain regions increase with brain size at different rates, these distinct allometries can allow for differential investment among sensory modalities. As predicted by mosaic evolution, species ecology was associated with some aspects of brain region investment. Nest architecture variation was not associated with brain investment differences, but the nocturnal genus Apoica had the largest antennal:optic volume ratio in its peripheral sensory lobes. Investment in central processing tissues was not related to nocturnality, a pattern also noted in mammals. The plasticity of neural connections in central regions may accommodate evolutionary shifts in input from the periphery with relatively minor changes in volume. © 2013 S. Karger AG, Basel.

Differences in the emergent coding properties of cortical and striatal ensembles

PubMed Central

Ma, L.; Hyman, J.M.; Lindsay, A.J.; Phillips, A.G.; Seamans, J.K.

2016-01-01

The function of a given brain region is often defined by the coding properties of its individual neurons, yet how this information is combined at the ensemble level is an equally important consideration. In the present study, multiple neurons from the anterior cingulate cortex (ACC) and the dorsal striatum (DS) were recorded simultaneously as rats performed different sequences of the same three actions. Sequence and lever decoding was remarkably similar on a per-neuron basis in the two regions. At the ensemble level, sequence-specific representations in the DS appeared synchronously but transiently along with the representation of lever location, while these two streams of information appeared independently and asynchronously in the ACC. As a result the ACC achieved superior ensemble decoding accuracy overall. Thus, the manner in which information was combined across neurons in an ensemble determined the functional separation of the ACC and DS on this task. PMID:24974796

Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance.

PubMed

Liebe, Stefanie; Hoerzer, Gregor M; Logothetis, Nikos K; Rainer, Gregor

2012-01-29

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria

PubMed Central

Dende, Chaitanya; Meena, Jairam; Nagarajan, Perumal; Panda, Amulya K.; Rangarajan, Pundi N.; Padmanaban, Govindarajan

2015-01-01

Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8+ T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. PMID:26227888

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

Simultaneous imaging of neural activity in three dimensions

PubMed Central

Quirin, Sean; Jackson, Jesse; Peterka, Darcy S.; Yuste, Rafael

2014-01-01

We introduce a scanless optical method to image neuronal activity in three dimensions simultaneously. Using a spatial light modulator and a custom-designed phase mask, we illuminate and collect light simultaneously from different focal planes and perform calcium imaging of neuronal activity in vitro and in vivo. This method, combining structured illumination with volume projection imaging, could be used as a technological platform for brain activity mapping. PMID:24772066

Application of probabilistically weighted graphs to image-based diagnosis of Alzheimer's disease using diffusion MRI

NASA Astrophysics Data System (ADS)

Maryam, Syeda; McCrackin, Laura; Crowley, Mark; Rathi, Yogesh; Michailovich, Oleg

2017-03-01

The world's aging population has given rise to an increasing awareness towards neurodegenerative disorders, including Alzheimers Disease (AD). Treatment options for AD are currently limited, but it is believed that future success depends on our ability to detect the onset of the disease in its early stages. The most frequently used tools for this include neuropsychological assessments, along with genetic, proteomic, and image-based diagnosis. Recently, the applicability of Diffusion Magnetic Resonance Imaging (dMRI) analysis for early diagnosis of AD has also been reported. The sensitivity of dMRI to the microstructural organization of cerebral tissue makes it particularly well-suited to detecting changes which are known to occur in the early stages of AD. Existing dMRI approaches can be divided into two broad categories: region-based and tract-based. In this work, we propose a new approach, which extends region-based approaches to the simultaneous characterization of multiple brain regions. Given a predefined set of features derived from dMRI data, we compute the probabilistic distances between different brain regions and treat the resulting connectivity pattern as an undirected, fully-connected graph. The characteristics of this graph are then used as markers to discriminate between AD subjects and normal controls (NC). Although in this preliminary work we omit subjects in the prodromal stage of AD, mild cognitive impairment (MCI), our method demonstrates perfect separability between AD and NC subject groups with substantial margin, and thus holds promise for fine-grained stratification of NC, MCI and AD populations.

On characterizing population commonalities and subject variations in brain networks.

PubMed

Ghanbari, Yasser; Bloy, Luke; Tunc, Birkan; Shankar, Varsha; Roberts, Timothy P L; Edgar, J Christopher; Schultz, Robert T; Verma, Ragini

2017-05-01

Brain networks based on resting state connectivity as well as inter-regional anatomical pathways obtained using diffusion imaging have provided insight into pathology and development. Such work has underscored the need for methods that can extract sub-networks that can accurately capture the connectivity patterns of the underlying population while simultaneously describing the variation of sub-networks at the subject level. We have designed a multi-layer graph clustering method that extracts clusters of nodes, called 'network hubs', which display higher levels of connectivity within the cluster than to the rest of the brain. The method determines an atlas of network hubs that describes the population, as well as weights that characterize subject-wise variation in terms of within- and between-hub connectivity. This lowers the dimensionality of brain networks, thereby providing a representation amenable to statistical analyses. The applicability of the proposed technique is demonstrated by extracting an atlas of network hubs for a population of typically developing controls (TDCs) as well as children with autism spectrum disorder (ASD), and using the structural and functional networks of a population to determine the subject-level variation of these hubs and their inter-connectivity. These hubs are then used to compare ASD and TDCs. Our method is generalizable to any population whose connectivity (structural or functional) can be captured via non-negative network graphs. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain-state dependent astrocytic Ca2+ signals are coupled to both positive and negative BOLD-fMRI signals.

PubMed

Wang, Maosen; He, Yi; Sejnowski, Terrence J; Yu, Xin

2018-02-13

Astrocytic Ca 2+ -mediated gliovascular interactions regulate the neurovascular network in situ and in vivo. However, it is difficult to measure directly both the astrocytic activity and fMRI to relate the various forms of blood-oxygen-level-dependent (BOLD) signaling to brain states under normal and pathological conditions. In this study, fMRI and GCaMP-mediated Ca 2+ optical fiber recordings revealed distinct evoked astrocytic Ca 2+ signals that were coupled with positive BOLD signals and intrinsic astrocytic Ca 2+ signals that were coupled with negative BOLD signals. Both evoked and intrinsic astrocytic calcium signal could occur concurrently or respectively during stimulation. The intrinsic astrocytic calcium signal can be detected globally in multiple cortical sites in contrast to the evoked astrocytic calcium signal only detected at the activated cortical region. Unlike propagating Ca 2+ waves in spreading depolarization/depression, the intrinsic Ca 2+ spikes occurred simultaneously in both hemispheres and were initiated upon the activation of the central thalamus and midbrain reticular formation. The occurrence of the intrinsic astrocytic calcium signal is strongly coincident with an increased EEG power level of the brain resting-state fluctuation. These results demonstrate highly correlated astrocytic Ca 2+ spikes with bidirectional fMRI signals based on the thalamic regulation of cortical states, depicting a brain-state dependency of both astrocytic Ca 2+ and BOLD fMRI signals.

The relationship between spatial configuration and functional connectivity of brain regions

PubMed Central

Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C

2018-01-01

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used ‘functional connectivity fingerprints’ to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. PMID:29451491

Poststroke delusions: What about the neuroanatomical and neurofunctional basis?

PubMed

Torrisi, Michele; De Luca, Rosaria; Pollicino, Patrizia; Leonardi, Simona; Marino, Silvia; Maresca, Giuseppa; Maggio, Maria Grazia; Piccolo, Adriana; Bramanti, Placido; Calabrò, Rocco Salvatore

2018-01-19

Delusion is a belief about yourself, people, or events that has no accordance with reality. Although it is known that stroke could cause various psychiatric and psychological effects, including depression, anxiety, and aggressiveness, psychotic symptoms, especially delusions, are rather uncommon. The most investigated poststroke delusions are paranoid type, nihilistic, and Fregoli syndrome. We will describe two patients showing delusion symptoms (Cotard-like and erotomanic ones) that occurred after a stroke involving the right temporal lobe, the basal ganglia and insular region, persisting for a long period after the stroke onset. We have, therefore, supposed that the simultaneous involvement of these brain areas could be involved in the neuroanatomical basis of delusions, as also demonstrated by the neurofunctional evaluation.

Category representations in the brain are both discretely localized and widely distributed.

PubMed

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.

Weight Perturbation Alters Leptin Signal Transduction in a Region-Specific Manner throughout the Brain

PubMed Central

Morabito, Michael V.; Ravussin, Yann; Mueller, Bridget R.; Skowronski, Alicja A.; Watanabe, Kazuhisa; Foo, Kylie S.; Lee, Samuel X.; Lehmann, Anders; Hjorth, Stephan; Zeltser, Lori M.; LeDuc, Charles A.; Leibel, Rudolph L.

2017-01-01

Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minutes following 3 mg/kg intraperitoneal leptin. HFD attenuated leptin sensing throughout the brain, but weight loss did not restore central leptin signaling to control levels in several brain regions important in energy homeostasis, including the arcuate and dorsomedial hypothalamic nuclei. Effects of diet on leptin signaling varied by brain region, with results dependent on the method of weight loss (restriction of calories of HFD, ad lib intake of standard mouse chow). High fat diet attenuates leptin signaling throughout the brain, but some brain regions maintain their ability to sense leptin. Weight loss restores leptin sensing to some degree in most (but not all) brain regions, while other brain regions display hypersensitivity to leptin following weight loss. Normal leptin sensing was restored in several brain regions, with the pattern of restoration dependent on the method of weight loss. PMID:28107353

Different Simultaneous Sleep States in the Hippocampus and Neocortex

PubMed Central

Emrick, Joshua J.; Gross, Brooks A.; Riley, Brett T.; Poe, Gina R.

2016-01-01

Study Objectives: Investigators assign sleep-waking states using brain activity collected from a single site, with the assumption that states occur at the same time throughout the brain. We sought to determine if sleep-waking states differ between two separate structures: the hippocampus and neocortex. Methods: We measured electrical signals (electroencephalograms and electromyograms) during sleep from the hippocampus and neocortex of five freely behaving adult male rats. We assigned sleep-waking states in 10-sec epochs based on standard scoring criteria across a 4-h recording, then analyzed and compared states and signals from simultaneous epochs between sites. Results: We found that the total amount of each state, assigned independently using the hippocampal and neocortical signals, was similar between the hippocampus and neocortex. However, states at simultaneous epochs were different as often as they were the same (P = 0.82). Furthermore, we found that the progression of states often flowed through asynchronous state-pairs led by the hippocampus. For example, the hippocampus progressed from transition-to-rapid eye movement sleep to rapid eye movement sleep before the neocortex more often than in synchrony with the neocortex (38.7 ± 16.2% versus 15.8 ± 5.6% mean ± standard error of the mean). Conclusions: We demonstrate that hippocampal and neocortical sleep-waking states often differ in the same epoch. Consequently, electrode location affects estimates of sleep architecture, state transition timing, and perhaps even percentage of time in sleep states. Therefore, under normal conditions, models assuming brain state homogeneity should not be applied to the sleeping or waking brain. Citation: Emrick JJ, Gross BA, Riley BT, Poe GR. Different simultaneous sleep states in the hippocampus and neocortex. SLEEP 2016;39(12):2201–2209. PMID:27748240

[Modeling of mixed infection by tick-borne encephalitis and Powassan viruses in mice].

PubMed

Khozinskaia, G A; Pogodina, V V

1982-01-01

Simultaneous inoculation of mice with tick-borne and Powassan viruses was shown, depending on experimental conditions, to result either in stimulation of infection or its unchanged course as compared with monoinfection and inoculation with the viruses at 2--3-week intervals in cross protection of mice against the superinfecting virus. Simultaneous inoculation of mice with the two viruses was accompanied by their multiplication in the blood and brains of mice and formation of antihemagglutinating antibodies to each of them. In the virus population in the brains of mice there was either formation of a mixture of two viruses or their phenotypic mixing. In cross protection, multiplication of the superinfecting virus in the blood and brain of mice was slightly inhibited, the antihemagglutinating antibody to a second virus either did not form or appeared in low titres.

Topological Organization of Functional Brain Networks in Healthy Children: Differences in Relation to Age, Sex, and Intelligence

PubMed Central

Wu, Kai; Taki, Yasuyuki; Sato, Kazunori; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Thyreau, Benjamin; He, Yong; Evans, Alan C.; Li, Xiaobo; Kawashima, Ryuta; Fukuda, Hiroshi

2013-01-01

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence. PMID:23390528

Topological organization of functional brain networks in healthy children: differences in relation to age, sex, and intelligence.

PubMed

Wu, Kai; Taki, Yasuyuki; Sato, Kazunori; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Thyreau, Benjamin; He, Yong; Evans, Alan C; Li, Xiaobo; Kawashima, Ryuta; Fukuda, Hiroshi

2013-01-01

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.

Brain activity underlying auditory perceptual learning during short period training: simultaneous fMRI and EEG recording

PubMed Central

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

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Yartsev, Slav; Yaremko, Brian

2011-07-15

Purpose: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lowermore » dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.« less

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

PubMed Central

Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-01-01

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. PMID:26125597

Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

PubMed

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.

Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

NASA Astrophysics Data System (ADS)

Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

2014-03-01

The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

“Optical communication with brain cells by means of an implanted duplex micro-device with optogenetics and Ca2+ fluoroimaging”

PubMed Central

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

The influence of complex and threatening environments in early life on brain size and behaviour.

PubMed

DePasquale, C; Neuberger, T; Hirrlinger, A M; Braithwaite, V A

2016-01-27

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. © 2016 The Authors.

The influence of complex and threatening environments in early life on brain size and behaviour

PubMed Central

Neuberger, T.; Hirrlinger, A. M.; Braithwaite, V. A.

2016-01-01

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. PMID:26817780

“Optical communication with brain cells by means of an implanted duplex micro-device with optogenetics and Ca2+ fluoroimaging”

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.

Time-reversal Techniques in Ultrasound-assisted Convection-enhanced Drug Delivery to the Brain: Technology Development and In Vivo Evaluation

PubMed Central

Lewis, George K.; Guarino, Sabrina; Gandhi, Gaurav; Filinger, Laurent; Lewis, George K.; Olbricht, Willam L.; Sarvazyan, Armen

2011-01-01

We describe a drug delivery method that combines Time-Reversal Acoustics (TRA) with Convection-Enhanced Delivery (CED) to improve the delivery of therapeutics to the interstitium of the brain. The Ultrasound-assisted CED approach (UCED) circumvents the blood-brain barrier by infusing compounds through a cannula that is inserted into the brain while simultaneously delivering ultrasound to improve the penetration of pharmaceuticals. CED without ultrasound-assistance has been used to treat a variety of neural disorders, including glioblastoma multiforme, a malignancy that presents a very poor prognosis for patients. We describe a novel system that is used to infuse fluids into the brain parenchyma while simultaneously exposing the tissue to safe levels of 1-MHz, low intensity, ultrasound energy. The system includes a combined infusion needle-hydrophone, a 10-channel ultralow-output impedance amplifier, a broad-band ultrasound resonator, and MatLab®-based TRA control and user-interface. TRA allows easy coupling of ultrasound therapy through the skull without complex phase-correction and array design. The smart targeting UCED system has been tested in vivo and results show it provides 1.5-mm spatial resolution for UCED and improves tracer distribution in the brain over CED alone. PMID:21881622

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

PubMed

Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

2017-03-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. Copyright © 2017 the American Physiological Society.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip

PubMed Central

Dauth, Stephanie; Maoz, Ben M.; Sheehy, Sean P.; Hemphill, Matthew A.; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M.; Budnik, Bogdan

2017-01-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. PMID:28031399

Strength of hand preference and dual task performance by common marmosets.

PubMed

Piddington, T; Rogers, L J

2013-01-01

Study of avian and piscine species has shown that animals with stronger lateralization of the brain are able to perform two tasks presented simultaneously better than can animals with weaker lateralization. We investigated whether this might apply also to primates by testing common marmosets to see whether there is a relationship between the strength of hand preference, as an indicator of strength of brain lateralization, and the ability to carry out two tasks simultaneously. A model predator was introduced into the testing room while the marmoset was foraging. Marmosets with stronger hand preferences detected the 'predator' after shorter latency than those with weaker hand preferences. Furthermore, the marmosets with stronger hand preferences produced more mobbing (tsik) vocalizations when they reacted to the predators than did those with weaker hand preferences. There was no such association between hand preference and either latency to respond to the predator or mobbing reaction when the marmosets were not foraging at the time the predator was introduced. Hence, strength of lateralization is associated with the ability to perform foraging and predator detection simultaneously. These results are discussed with reference to the evolution of brain lateralization.

Centrality of Social Interaction in Human Brain Function.

PubMed

Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

2015-10-07

People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

The relationship between spatial configuration and functional connectivity of brain regions.

PubMed

Bijsterbosch, Janine Diane; Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C; Harrison, Samuel J; Smith, Stephen M

2018-02-16

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used 'functional connectivity fingerprints' to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. © 2018, Bijsterbosch et al.

The time course of auditory-visual processing of speech and body actions: evidence for the simultaneous activation of an extended neural network for semantic processing.

PubMed

Meyer, Georg F; Harrison, Neil R; Wuerger, Sophie M

2013-08-01

An extensive network of cortical areas is involved in multisensory object and action recognition. This network draws on inferior frontal, posterior temporal, and parietal areas; activity is modulated by familiarity and the semantic congruency of auditory and visual component signals even if semantic incongruences are created by combining visual and auditory signals representing very different signal categories, such as speech and whole body actions. Here we present results from a high-density ERP study designed to examine the time-course and source location of responses to semantically congruent and incongruent audiovisual speech and body actions to explore whether the network involved in action recognition consists of a hierarchy of sequentially activated processing modules or a network of simultaneously active processing sites. We report two main results:1) There are no significant early differences in the processing of congruent and incongruent audiovisual action sequences. The earliest difference between congruent and incongruent audiovisual stimuli occurs between 240 and 280 ms after stimulus onset in the left temporal region. Between 340 and 420 ms, semantic congruence modulates responses in central and right frontal areas. Late differences (after 460 ms) occur bilaterally in frontal areas.2) Source localisation (dipole modelling and LORETA) reveals that an extended network encompassing inferior frontal, temporal, parasaggital, and superior parietal sites are simultaneously active between 180 and 420 ms to process auditory–visual action sequences. Early activation (before 120 ms) can be explained by activity in mainly sensory cortices. . The simultaneous activation of an extended network between 180 and 420 ms is consistent with models that posit parallel processing of complex action sequences in frontal, temporal and parietal areas rather than models that postulate hierarchical processing in a sequence of brain regions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Study of the functional hyperconnectivity between couples of pilots during flight simulation: an EEG hyperscanning study.

PubMed

Astolfi, L; Toppi, J; Borghini, G; Vecchiato, G; Isabella, R; De Vico Fallani, F; Cincotti, F; Salinari, S; Mattia, D; He, B; Caltagirone, C; Babiloni, F

2011-01-01

Brain Hyperscanning, i.e. the simultaneous recording of the cerebral activity of different human subjects involved in interaction tasks, is a very recent field of Neuroscience aiming at understanding the cerebral processes generating and generated by social interactions. This approach allows the observation and modeling of the neural signature specifically dependent on the interaction between subjects, and, even more interestingly, of the functional links existing between the activities in the brains of the subjects interacting together. In this EEG hyperscanning study we explored the functional hyperconnectivity between the activity in different scalp sites of couples of Civil Aviation Pilots during different phases of a flight reproduced in a flight simulator. Results shown a dense network of connections between the two brains in the takeoff and landing phases, when the cooperation between them is maximal, in contrast with phases during which the activity of the two pilots was independent, when no or quite few links were shown. These results confirms that the study of the brain connectivity between the activity simultaneously acquired in human brains during interaction tasks can provide important information about the neural basis of the "spirit of the group".

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease.

PubMed

Dagan, Moria; Herman, Talia; Harrison, Rachel; Zhou, Junhong; Giladi, Nir; Ruffini, Giulio; Manor, Brad; Hausdorff, Jeffrey M

2018-04-01

Recent findings suggest that transcranial direct current stimulation of the primary motor cortex may ameliorate freezing of gait. However, the effects of multitarget simultaneous stimulation of motor and cognitive networks are mostly unknown. The objective of this study was to evaluate the effects of multitarget transcranial direct current stimulation of the primary motor cortex and left dorsolateral prefrontal cortex on freezing of gait and related outcomes. Twenty patients with Parkinson's disease and freezing of gait received 20 minutes of transcranial direct current stimulation on 3 separate visits. Transcranial direct current stimulation targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously, primary motor cortex only, or sham stimulation (order randomized and double-blinded assessments). Participants completed a freezing of gait-provoking test, the Timed Up and Go, and the Stroop test before and after each transcranial direct current stimulation session. Performance on the freezing of gait-provoking test (P = 0.010), Timed Up and Go (P = 0.006), and the Stroop test (P = 0.016) improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after primary motor cortex only or sham stimulation. Transcranial direct current stimulation designed to simultaneously target motor and cognitive regions apparently induces immediate aftereffects in the brain that translate into reduced freezing of gait and improvements in executive function and mobility. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

A viscoelastic analysis of the P56 mouse brain under large-deformation dynamic indentation.

PubMed

MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

2017-01-15

The brain is a complex organ made up of many different functional and structural regions consisting of different types of cells such as neurons and glia, as well as complex anatomical geometries. It is hypothesized that the different regions of the brain exhibit significantly different mechanical properties which may be attributed to the diversity of cells within individual brain regions. The regional viscoelastic properties of P56 mouse brain tissue, up to 70μm displacement, are presented and discussed in the context of traumatic brain injury, particularly how the different regions of the brain respond to mechanical loads. Force-relaxation data obtained from micro-indentation measurements were fit to both linear and quasi-linear viscoelastic models to determine the time and frequency domain viscoelastic response of the pons, cortex, medulla oblongata, cerebellum, and thalamus. The damping ratio of each region was also determined. Each region was found to have a unique mechanical response to the applied displacement, with the pons and thalamus exhibiting the largest and smallest force-response, respectively. All brain regions appear to have an optimal frequency for the dissipation of energies which lies between 1 and 10Hz. We present the first mechanical characterization of the viscoelastic response for different regions of mouse brain. Force-relaxation tests are performed under large strain dynamic micro-indentation, and viscoelastic models are used subsequently, providing time-dependent mechanical properties of brain tissue under loading conditions comparable to what is experienced in TBI. The unique mechanical properties of different brain regions are highlighted, with substantial variations in the viscoelastic properties and damping ratio of each region. Cortex and pons were the stiffest regions, while the thalamus and medulla were most compliant. The cerebellum and thalamus had highest damping ratio values and those of the medulla were lowest. The reported material parameters can be implemented into finite element computer models of the mouse to investigate the effects of trauma on individual brain regions. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

GABA-A receptors in mPOAH simultaneously regulate sleep and body temperature in freely moving rats.

PubMed

Jha, S K; Yadav, V; Mallick, B N

2001-09-01

Sleep-wakefulness and body temperature are two circadian rhythmic biological phenomena. The role of GABAergic inputs in the medial preoptico-anterior hypothalamus (mPOAH) on simultaneous regulation of those phenomena was investigated in freely moving normally behaving rats. The GABA-A receptors were blocked by microinjecting picrotoxin, and the effects on electrophysiological parameters signifying sleep-wakefulness, rectal temperature and brain temperature were recorded simultaneously. The results suggest that, normally, GABA in the medial preoptic area acts through GABA-A receptor that induces sleep and prevents an excessive rise in body temperature. However, the results do not allow us to comment on the cause and effect relationship, if any, between changes in sleep-wakefulness and body temperature. The changes in brain and rectal temperatures showed a positive correlation, however, the former varied within a narrower range than that of the latter.

Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

NASA Astrophysics Data System (ADS)

Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

2015-03-01

Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

Human brains found in a fire-affected 4000-years old Bronze Age tumulus layer rich in soil alkalines and boron in Kutahya, Western Anatolia.

PubMed

Altinoz, M A; Ince, B; Sav, A; Dincer, A; Cengiz, S; Mercan, S; Yazici, Z; Bilgen, M N

2014-02-01

Undecomposed human bodies and organs always attracted interest in terms of understanding biological tissue stability and immortality. Amongst these, cases of natural mummification found in glaciers, bog sediments and deserts caused even more attention. In 2010, an archeological excavation of a Bronze Age layer in a tumulus near the Western Anatolia city Kütahya revealed fire affected regions with burnt human skeletons and charred wooden objects. Inside of the cracked skulls, undecomposed brains were discernible. To analyze the burial taphonomy of the rare phenomenon of brain preservation, we analyzed brains, bone, teeth and surrounding soils elements using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Adipocere formation or saponification of postmortem tissue fat requires high levels of alkalinity and especially potassium. Indeed, ICP-MS analysis of the brain, teeth and bone and also of the surrounding soil revealed high levels of potassium, magnesium, aluminum and boron, which are compatible with the famous role of Kütahya in tile production with its soil containing high level of alkalines and tile-glazing boron. Fatty acid chromatography revealed simultaneous saturation of fats and protection of fragile unsaturated fatty acids consistent with soil-presence of both pro-oxidant and anti-oxidant trace metals. Computerized tomography revealed protection of diencephalic, metencephalic and occipital tissue in one of the best-preserved specimens. Boron was previously found as an intentional preservative of Tutankhamen and Deir el Bahari mummies. Here, in natural soil with its insect-repellant, anti-bacterial and fire-resistance qualities it may be a factor to preserve heat-affected brains as almost bioporcellain specimens. Copyright © 2013 Elsevier GmbH. All rights reserved.

Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes.

PubMed

Hosseini, S M Hadi; Mazaika, Paul; Mauras, Nelly; Buckingham, Bruce; Weinzimer, Stuart A; Tsalikian, Eva; White, Neil H; Reiss, Allan L

2016-11-01

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Persistency and flexibility of complex brain networks underlie dual-task interference.

PubMed

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley Periodicals, Inc.

GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice

PubMed Central

Matagne, Valérie; Ghata, Adeline; Villard, Laurent; Roux, Jean-Christophe

2014-01-01

Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional- and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder. PMID:24667344

Detection of Alzheimer's disease using group lasso SVM-based region selection

NASA Astrophysics Data System (ADS)

Sun, Zhuo; Fan, Yong; Lelieveldt, Boudewijn P. F.; van de Giessen, Martijn

2015-03-01

Alzheimer's disease (AD) is one of the most frequent forms of dementia and an increasing challenging public health problem. In the last two decades, structural magnetic resonance imaging (MRI) has shown potential in distinguishing patients with Alzheimer's disease and elderly controls (CN). To obtain AD-specific biomarkers, previous research used either statistical testing to find statistically significant different regions between the two clinical groups, or l1 sparse learning to select isolated features in the image domain. In this paper, we propose a new framework that uses structural MRI to simultaneously distinguish the two clinical groups and find the bio-markers of AD, using a group lasso support vector machine (SVM). The group lasso term (mixed l1- l2 norm) introduces anatomical information from the image domain into the feature domain, such that the resulting set of selected voxels are more meaningful than the l1 sparse SVM. Because of large inter-structure size variation, we introduce a group specific normalization factor to deal with the structure size bias. Experiments have been performed on a well-designed AD vs. CN dataset1 to validate our method. Comparing to the l1 sparse SVM approach, our method achieved better classification performance and a more meaningful biomarker selection. When we vary the training set, the selected regions by our method were more stable than the l1 sparse SVM. Classification experiments showed that our group normalization lead to higher classification accuracy with fewer selected regions than the non-normalized method. Comparing to the state-of-art AD vs. CN classification methods, our approach not only obtains a high accuracy with the same dataset, but more importantly, we simultaneously find the brain anatomies that are closely related to the disease.

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep

PubMed Central

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

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep.

PubMed

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.

Localization of spontaneous bursting neuronal activity in the preterm human brain with simultaneous EEG-fMRI.

PubMed

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.

Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI.

PubMed

Olcott, Peter; Kim, Ealgoo; Hong, Keyjo; Lee, Brian J; Grant, Alexander M; Chang, Chen-Ming; Glover, Gary; Levin, Craig S

2015-05-07

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI

NASA Astrophysics Data System (ADS)

Olcott, Peter; Kim, Ealgoo; Hong, Keyjo; Lee, Brian J.; Grant, Alexander M.; Chang, Chen-Ming; Glover, Gary; Levin, Craig S.

2015-05-01

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

Alzheimer's disease against peptides products of enzymatic cleavage APP protein: Biological, pathobiological and physico-chemical properties of fibrillating peptides.

PubMed

Marszałek, Małgorzata

2017-05-17

Various peptides products of enzymatic cleavage of key for Alzheimer's disease Amyloid Precursor Protein (APP) are well known, but still are matter of scientific debate. The Aβ type products are especially challenging for experimental and medical research. This paper outlines several, still poorly known, biological and medical processes such as peptides biology, i.e., formation, biodistribution, translocation, transport and finally removal from brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine. In addition, the following studies concerning AD patients might prove challenging and simultaneously promising: peptides translocation through Blood-Brain - Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB) and their removal from the brain according to a new concept of glymphatic system; - diagnostic difficulties that stem from physico-chemical properties and the nature of proteins or fibrillating peptides itself like low concentration, short half-live and from experimental-technical problems as well like high adsorption or low solubility of Aβ, tau or amylin. The study of diagnostic parameters is very important, as it may better reflect early changes before the disease develops; one such parameter is the Aβ42/Aβ40 ratio, or the ratio with the total tau concentration combination and other new biomarkers like Aβ1-38; other factors include oxidative stress and inflammation process proteins, complement factor H, alpha-2-macroglobulin, or clusterin. The study of various forms of pathological amyloid deposits that emerge in different but specific brain regions AD patients seems to be crucial as well. The composition of the first initial pathological, pre-fibrillating monomers of fibrillating peptides and their role in AD development and disease progression have been described as well. They are even more challenging for science and simultaneously might be more promising in early diagnosis for AD patients. As always in science, research leads to endless discoveries and further inquiry. Fundamental problems in this field most probably are still far from being definitively comprehended, and multiple crucial questions await better answers. What we really need is to study more and deeper into this matter.

Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices.

PubMed

Wang, Ying; Lin, Xudong; Chen, Xi; Chen, Xian; Xu, Zhen; Zhang, Wenchong; Liao, Qinghai; Duan, Xin; Wang, Xin; Liu, Ming; Wang, Feng; He, Jufang; Shi, Peng

2017-10-01

Many nanomaterials can be used as sensors or transducers in biomedical research and they form the essential components of transformative novel biotechnologies. In this study, we present an all-optical method for tetherless remote control of neural activity using fully implantable micro-devices based on upconversion technology. Upconversion nanoparticles (UCNPs) were used as transducers to convert near-infrared (NIR) energy to visible light in order to stimulate neurons expressing different opsin proteins. In our setup, UCNPs were packaged in a glass micro-optrode to form an implantable device with superb long-term biocompatibility. We showed that remotely applied NIR illumination is able to reliably trigger spiking activity in rat brains. In combination with a robotic laser projection system, the upconversion-based tetherless neural stimulation technique was implemented to modulate brain activity in various regions, including the striatum, ventral tegmental area, and visual cortex. Using this system, we were able to achieve behavioral conditioning in freely moving animals. Notably, our microscale device was at least one order of magnitude smaller in size (∼100 μm in diameter) and two orders of magnitude lighter in weight (less than 1 mg) than existing wireless optogenetic devices based on light-emitting diodes. This feature allows simultaneous implantation of multiple UCNP-optrodes to achieve modulation of brain function to control complex animal behavior. We believe that this technology not only represents a novel practical application of upconversion nanomaterials, but also opens up new possibilities for remote control of neural activity in the brains of behaving animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study.

PubMed

Lavigne, Katie M; Woodward, Todd S

2018-04-01

Hypercoupling of activity in speech-perception-specific brain networks has been proposed to play a role in the generation of auditory-verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task-based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI-CPCA), which allowed for comparison of task-related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory-motor, (b) language processing, and (c) default-mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory-motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non-AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech-perception-related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation. © 2017 Wiley Periodicals, Inc.

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

PubMed

Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

2011-09-01

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Brain networks for confidence weighting and hierarchical inference during probabilistic learning.

PubMed

Meyniel, Florent; Dehaene, Stanislas

2017-05-09

Learning is difficult when the world fluctuates randomly and ceaselessly. Classical learning algorithms, such as the delta rule with constant learning rate, are not optimal. Mathematically, the optimal learning rule requires weighting prior knowledge and incoming evidence according to their respective reliabilities. This "confidence weighting" implies the maintenance of an accurate estimate of the reliability of what has been learned. Here, using fMRI and an ideal-observer analysis, we demonstrate that the brain's learning algorithm relies on confidence weighting. While in the fMRI scanner, human adults attempted to learn the transition probabilities underlying an auditory or visual sequence, and reported their confidence in those estimates. They knew that these transition probabilities could change simultaneously at unpredicted moments, and therefore that the learning problem was inherently hierarchical. Subjective confidence reports tightly followed the predictions derived from the ideal observer. In particular, subjects managed to attach distinct levels of confidence to each learned transition probability, as required by Bayes-optimal inference. Distinct brain areas tracked the likelihood of new observations given current predictions, and the confidence in those predictions. Both signals were combined in the right inferior frontal gyrus, where they operated in agreement with the confidence-weighting model. This brain region also presented signatures of a hierarchical process that disentangles distinct sources of uncertainty. Together, our results provide evidence that the sense of confidence is an essential ingredient of probabilistic learning in the human brain, and that the right inferior frontal gyrus hosts a confidence-based statistical learning algorithm for auditory and visual sequences.

Experimental validation of the influence of white matter anisotropy on the intracranial EEG forward solution.

PubMed

Bangera, Nitin B; Schomer, Donald L; Dehghani, Nima; Ulbert, Istvan; Cash, Sydney; Papavasiliou, Steve; Eisenberg, Solomon R; Dale, Anders M; Halgren, Eric

2010-12-01

Forward solutions with different levels of complexity are employed for localization of current generators, which are responsible for the electric and magnetic fields measured from the human brain. The influence of brain anisotropy on the forward solution is poorly understood. The goal of this study is to validate an anisotropic model for the intracranial electric forward solution by comparing with the directly measured 'gold standard'. Dipolar sources are created at known locations in the brain and intracranial electroencephalogram (EEG) is recorded simultaneously. Isotropic models with increasing level of complexity are generated along with anisotropic models based on Diffusion tensor imaging (DTI). A Finite Element Method based forward solution is calculated and validated using the measured data. Major findings are (1) An anisotropic model with a linear scaling between the eigenvalues of the electrical conductivity tensor and water self-diffusion tensor in brain tissue is validated. The greatest improvement was obtained when the stimulation site is close to a region of high anisotropy. The model with a global anisotropic ratio of 10:1 between the eigenvalues (parallel: tangential to the fiber direction) has the worst performance of all the anisotropic models. (2) Inclusion of cerebrospinal fluid as well as brain anisotropy in the forward model is necessary for an accurate description of the electric field inside the skull. The results indicate that an anisotropic model based on the DTI can be constructed non-invasively and shows an improved performance when compared to the isotropic models for the calculation of the intracranial EEG forward solution.

Regional brain volumetry and brain function in severely brain-injured patients.

PubMed

Annen, Jitka; Frasso, Gianluca; Crone, Julia Sophia; Heine, Lizette; Di Perri, Carol; Martial, Charlotte; Cassol, Helena; Demertzi, Athena; Naccache, Lionel; Laureys, Steven

2018-04-01

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853. © 2018 American Neurological Association.

Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura.

PubMed

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud

2017-06-01

See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier disruption as a possible mechanism linking aura and headache.awx089media15422686892001. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Automated brain tumor segmentation in magnetic resonance imaging based on sliding-window technique and symmetry analysis.

PubMed

Lian, Yanyun; Song, Zhijian

2014-01-01

Brain tumor segmentation from magnetic resonance imaging (MRI) is an important step toward surgical planning, treatment planning, monitoring of therapy. However, manual tumor segmentation commonly used in clinic is time-consuming and challenging, and none of the existed automated methods are highly robust, reliable and efficient in clinic application. An accurate and automated tumor segmentation method has been developed for brain tumor segmentation that will provide reproducible and objective results close to manual segmentation results. Based on the symmetry of human brain, we employed sliding-window technique and correlation coefficient to locate the tumor position. At first, the image to be segmented was normalized, rotated, denoised, and bisected. Subsequently, through vertical and horizontal sliding-windows technique in turn, that is, two windows in the left and the right part of brain image moving simultaneously pixel by pixel in two parts of brain image, along with calculating of correlation coefficient of two windows, two windows with minimal correlation coefficient were obtained, and the window with bigger average gray value is the location of tumor and the pixel with biggest gray value is the locating point of tumor. At last, the segmentation threshold was decided by the average gray value of the pixels in the square with center at the locating point and 10 pixels of side length, and threshold segmentation and morphological operations were used to acquire the final tumor region. The method was evaluated on 3D FSPGR brain MR images of 10 patients. As a result, the average ratio of correct location was 93.4% for 575 slices containing tumor, the average Dice similarity coefficient was 0.77 for one scan, and the average time spent on one scan was 40 seconds. An fully automated, simple and efficient segmentation method for brain tumor is proposed and promising for future clinic use. Correlation coefficient is a new and effective feature for tumor location.

Brain-shift compensation using intraoperative ultrasound and constraint-based biomechanical simulation.

PubMed

Morin, Fanny; Courtecuisse, Hadrien; Reinertsen, Ingerid; Le Lann, Florian; Palombi, Olivier; Payan, Yohan; Chabanas, Matthieu

2017-08-01

During brain tumor surgery, planning and guidance are based on preoperative images which do not account for brain-shift. However, this deformation is a major source of error in image-guided neurosurgery and affects the accuracy of the procedure. In this paper, we present a constraint-based biomechanical simulation method to compensate for craniotomy-induced brain-shift that integrates the deformations of the blood vessels and cortical surface, using a single intraoperative ultrasound acquisition. Prior to surgery, a patient-specific biomechanical model is built from preoperative images, accounting for the vascular tree in the tumor region and brain soft tissues. Intraoperatively, a navigated ultrasound acquisition is performed directly in contact with the organ. Doppler and B-mode images are recorded simultaneously, enabling the extraction of the blood vessels and probe footprint, respectively. A constraint-based simulation is then executed to register the pre- and intraoperative vascular trees as well as the cortical surface with the probe footprint. Finally, preoperative images are updated to provide the surgeon with images corresponding to the current brain shape for navigation. The robustness of our method is first assessed using sparse and noisy synthetic data. In addition, quantitative results for five clinical cases are provided, first using landmarks set on blood vessels, then based on anatomical structures delineated in medical images. The average distances between paired vessels landmarks ranged from 3.51 to 7.32 (in mm) before compensation. With our method, on average 67% of the brain-shift is corrected (range [1.26; 2.33]) against 57% using one of the closest existing works (range [1.71; 2.84]). Finally, our method is proven to be fully compatible with a surgical workflow in terms of execution times and user interactions. In this paper, a new constraint-based biomechanical simulation method is proposed to compensate for craniotomy-induced brain-shift. While being efficient to correct this deformation, the method is fully integrable in a clinical process. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in east greenland polar bears (Ursus maritimus).

PubMed

Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune

2013-03-01

The present study investigated the comparative accumulation of perfluoroalkyl acids (PFAAs) in eight brain regions of polar bears (Ursus maritimus, n = 19) collected in 2006 from Scoresby Sound, East Greenland. The PFAAs studied were perfluoroalkyl carboxylates (PFCAs, C(6) -C(15) chain lengths) and sulfonates (C(4) , C(6) , C(8) , and C(10) chain lengths) as well as selected precursors including perfluorooctane sulfonamide. On a wet-weight basis, blood-brain barrier transport of PFAAs occurred for all brain regions, although inner regions of the brain closer to incoming blood flow (pons/medulla, thalamus, and hypothalamus) contained consistently higher PFAA concentrations compared to outer brain regions (cerebellum, striatum, and frontal, occipital, and temporal cortices). For pons/medulla, thalamus, and hypothalamus, the most concentrated PFAAs were perfluorooctane sulfonate (PFOS), ranging from 47 to 58 ng/g wet weight, and perfluorotridecanoic acid, ranging from 43 to 49 ng/g wet weight. However, PFOS and the longer-chain PFCAs (C(10) -C(15) ) were significantly (p < 0.002) positively correlated with lipid content for all brain regions. Lipid-normalized PFOS and PFCA (C(10) -C(15) ) concentrations were not significantly (p > 0.05) different among brain regions. The burden of the sum of PFCAs, perfluoroalkyl sulfonates, and perfluorooctane sulfonamide in the brain (average mass, 392 g) was estimated to be 46 µg. The present study demonstrates that both PFCAs and perfluoroalkyl sulfonates cross the blood-brain barrier in polar bears and that wet-weight concentrations are brain region-specific. Copyright © 2012 SETAC.

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy.

PubMed

Hoch, M J; Chung, S; Ben-Eliezer, N; Bruno, M T; Fatterpekar, G M; Shepherd, T M

2016-06-01

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. © 2016 by American Journal of Neuroradiology.

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

PubMed

Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Will, B.E.; Rosenzweig, M.R.; Bennett, E.L.

1977-01-01

Enriched postlesion experience aided in overcoming effects of simultaneous bilateral cerebral lesions made at 30 days of age in one experiment with inbred Fischer rats and in a second experiment with the Berkeley S/sub 1/ strain. The lesions were directed to the occipital cortex, but in most cases there was also some impairment of the hippocampus. For 60 days after operations, half of the rats lived in small individual cages and half lived in groups in large enriched-environment cages. They were then pretrained and tested on the standard 12 Hebb-Williams problems. Daily injections of methamphetamine (vs. saline) during the periodmore » of differential experience in the first experiment produced no effect on the behavioral scores. The second experiment included groups that received only 2 hr/day of enriched experience, and they benefited as much as groups that remained in the enriched environment 24 hr/day. The results of both experiments demonstrated significant beneficial effects of environment when bilateral lesions were made at a later age and when the periods of enriched experience were shorter than had previously been tested. Two additional experiments revealed significant effects of both lesions and environment on weight and RNA/DNA of brain regions.« less

Imitating expressions: emotion-specific neural substrates in facial mimicry.

PubMed

Lee, Tien-Wen; Josephs, Oliver; Dolan, Raymond J; Critchley, Hugo D

2006-09-01

Intentionally adopting a discrete emotional facial expression can modulate the subjective feelings corresponding to that emotion; however, the underlying neural mechanism is poorly understood. We therefore used functional brain imaging (functional magnetic resonance imaging) to examine brain activity during intentional mimicry of emotional and non-emotional facial expressions and relate regional responses to the magnitude of expression-induced facial movement. Eighteen healthy subjects were scanned while imitating video clips depicting three emotional (sad, angry, happy), and two 'ingestive' (chewing and licking) facial expressions. Simultaneously, facial movement was monitored from displacement of fiducial markers (highly reflective dots) on each subject's face. Imitating emotional expressions enhanced activity within right inferior prefrontal cortex. This pattern was absent during passive viewing conditions. Moreover, the magnitude of facial movement during emotion-imitation predicted responses within right insula and motor/premotor cortices. Enhanced activity in ventromedial prefrontal cortex and frontal pole was observed during imitation of anger, in ventromedial prefrontal and rostral anterior cingulate during imitation of sadness and in striatal, amygdala and occipitotemporal during imitation of happiness. Our findings suggest a central role for right inferior frontal gyrus in the intentional imitation of emotional expressions. Further, by entering metrics for facial muscular change into analysis of brain imaging data, we highlight shared and discrete neural substrates supporting affective, action and social consequences of somatomotor emotional expression.

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Mental Task Evaluation for Hybrid NIRS-EEG Brain-Computer Interfaces

PubMed Central

Gupta, Rishabh; Falk, Tiago H.

2017-01-01

Based on recent electroencephalography (EEG) and near-infrared spectroscopy (NIRS) studies that showed that tasks such as motor imagery and mental arithmetic induce specific neural response patterns, we propose a hybrid brain-computer interface (hBCI) paradigm in which EEG and NIRS data are fused to improve binary classification performance. We recorded simultaneous NIRS-EEG data from nine participants performing seven mental tasks (word generation, mental rotation, subtraction, singing and navigation, and motor and face imagery). Classifiers were trained for each possible pair of tasks using (1) EEG features alone, (2) NIRS features alone, and (3) EEG and NIRS features combined, to identify the best task pairs and assess the usefulness of a multimodal approach. The NIRS-EEG approach led to an average increase in peak kappa of 0.03 when using features extracted from one-second windows (equivalent to an increase of 1.5% in classification accuracy for balanced classes). The increase was much stronger (0.20, corresponding to an 10% accuracy increase) when focusing on time windows of high NIRS performance. The EEG and NIRS analyses further unveiled relevant brain regions and important feature types. This work provides a basis for future NIRS-EEG hBCI studies aiming to improve classification performance toward more efficient and flexible BCIs. PMID:29181021

Learning and memory functions of the Basal Ganglia.

PubMed

Packard, Mark G; Knowlton, Barbara J

2002-01-01

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

PubMed

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds

PubMed Central

Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen

2013-01-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

PubMed

Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Temporal characteristics of audiovisual information processing.

PubMed

Fuhrmann Alpert, Galit; Hein, Grit; Tsai, Nancy; Naumer, Marcus J; Knight, Robert T

2008-05-14

In complex natural environments, auditory and visual information often have to be processed simultaneously. Previous functional magnetic resonance imaging (fMRI) studies focused on the spatial localization of brain areas involved in audiovisual (AV) information processing, but the temporal characteristics of AV information flow in these regions remained unclear. In this study, we used fMRI and a novel information-theoretic approach to study the flow of AV sensory information. Subjects passively perceived sounds and images of objects presented either alone or simultaneously. Applying the measure of mutual information, we computed for each voxel the latency in which the blood oxygenation level-dependent signal had the highest information content about the preceding stimulus. The results indicate that, after AV stimulation, the earliest informative activity occurs in right Heschl's gyrus, left primary visual cortex, and the posterior portion of the superior temporal gyrus, which is known as a region involved in object-related AV integration. Informative activity in the anterior portion of superior temporal gyrus, middle temporal gyrus, right occipital cortex, and inferior frontal cortex was found at a later latency. Moreover, AV presentation resulted in shorter latencies in multiple cortical areas compared with isolated auditory or visual presentation. The results provide evidence for bottom-up processing from primary sensory areas into higher association areas during AV integration in humans and suggest that AV presentation shortens processing time in early sensory cortices.

Common time-frequency analysis of local field potential and pyramidal cell activity in seizure-like events of the rat hippocampus

NASA Astrophysics Data System (ADS)

Cotic, M.; Chiu, A. W. L.; Jahromi, S. S.; Carlen, P. L.; Bardakjian, B. L.

2011-08-01

To study cell-field dynamics, physiologists simultaneously record local field potentials and the activity of individual cells from animals performing cognitive tasks, during various brain states or under pathological conditions. However, apart from spike shape and spike timing analyses, few studies have focused on elucidating the common time-frequency structure of local field activity relative to surrounding cells across different periods of phenomena. We have used two algorithms, multi-window time frequency analysis and wavelet phase coherence (WPC), to study common intracellular-extracellular (I-E) spectral features in spontaneous seizure-like events (SLEs) from rat hippocampal slices in a low magnesium epilepsy model. Both algorithms were applied to 'pairs' of simultaneously observed I-E signals from slices in the CA1 hippocampal region. Analyses were performed over a frequency range of 1-100 Hz. I-E spectral commonality varied in frequency and time. Higher commonality was observed from 1 to 15 Hz, and lower commonality was observed in the 15-100 Hz frequency range. WPC was lower in the non-SLE region compared to SLE activity; however, there was no statistical difference in the 30-45 Hz band between SLE and non-SLE modes. This work provides evidence of strong commonality in various frequency bands of I-E SLEs in the rat hippocampus, not only during SLEs but also immediately before and after.

Simultaneous pH-sensitive and oxygen-sensitive MRI of human gliomas at 3 T using multi-echo amine proton chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI).

PubMed

Harris, Robert J; Yao, Jingwen; Chakhoyan, Ararat; Raymond, Catalina; Leu, Kevin; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Salamon, Noriko; Pope, Whitney B; Cloughesy, Timothy F; Ellingson, Benjamin M

2018-04-06

To introduce a new pH-sensitive and oxygen-sensitive MRI technique using amine proton CEST echo spin-and-gradient echo (SAGE) EPI (CEST-SAGE-EPI). pH-weighting was obtained using CEST estimations of magnetization transfer ratio asymmetry (MTR asym ) at 3 ppm, and oxygen-weighting was obtained using R2' measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTR asym and R2' in normal-appearing white matter, T 2 hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas. Simulation and phantom results confirmed an increase in MTR asym with decreasing pH. The CEST-SAGE-EPI estimates of R 2 , R2*, and R2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R 2  = 6.2 mM -1 ·sec -1 and R2* = 6.9 mM -1 ·sec -1 ). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R 2 (R 2  = 0.9943) and multi-echo gradient-echo estimates of R2* (R 2  = 0.9727) were highly correlated. T 2 lesions had lower R2' and higher MTR asym compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R2' and MTR asym , indicating high hypoxia and acidity. The CEST-SAGE-EPI technique provides simultaneous pH-sensitive and oxygen-sensitive image contrasts for evaluation of the brain tumor microenvironment. Advantages include fast whole-brain acquisition, in-line B 0 correction, and simultaneous estimation of CEST effects, R 2 , R2*, and R2' at 3 T. © 2018 International Society for Magnetic Resonance in Medicine.

Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

PubMed

Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

2016-02-23

We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature.

PubMed

Smith, Stephen W; Ivancevich, Nikolas M; Lindsey, Brooks D; Whitman, John; Light, Edward; Fronheiser, Matthew; Nicoletto, Heather A; Laskowitz, Daniel T

2009-02-01

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time three-dimensional (3D) scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging (Durham, NC, USA) real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64 degrees pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128 degrees sector, two simultaneous parasagittal images merged into a 128 degrees x 64 degrees C-mode plane and a simultaneous 64 degrees axial image. Real-time 3D color Doppler scans from a skull phantom with latex blood vessel were obtained after contrast agent injection as a proof of concept. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

Novel bifunctional cap for simultaneous electroencephalography and transcranial electrical stimulation.

PubMed

Wunder, Sophia; Hunold, Alexander; Fiedler, Patrique; Schlegelmilch, Falk; Schellhorn, Klaus; Haueisen, Jens

2018-05-08

Neuromodulation induced by transcranial electric stimulation (TES) exhibited promising potential for clinical practice. However, the underlying mechanisms remain subject of research. The combination of TES and electroencephalography (EEG) offers great potential for investigating these mechanisms and brain function in general, especially when performed simultaneously. In conventional applications, the combination of EEG and TES suffers from limitations on the electrode level (gel for electrode-skin interface) and the usability level (preparation time, reproducibility of positioning). To overcome these limitations, we designed a bifunctional cap for simultaneous TES-EEG applications. We used novel electrode materials, namely textile stimulation electrodes and dry EEG electrodes integrated in a flexible textile cap. We verified the functionality of this cap by analysing the effect of TES on visual evoked potentials (VEPs). In accordance with previous reports using standard TES, the amplitude of the N75 component was significantly decreased post-stimulation, indicating the feasibility of using this novel flexible cap for simultaneous TES and EEG. Further, we found a significant reduction of the P100 component only during TES, indicating a different brain modulation effect during and after TES. In conclusion, the novel bifunctional cap offers a novel tool for simultaneous TES-EEG applications in clinical research, therapy monitoring and closed-loop stimulation.

A novel high electrode count spike recording array using an 81,920 pixel transimpedance amplifier-based imaging chip.

PubMed

Johnson, Lee J; Cohen, Ethan; Ilg, Doug; Klein, Richard; Skeath, Perry; Scribner, Dean A

2012-04-15

Microelectrode recording arrays of 60-100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 readout integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 μm. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (∼0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz. Published by Elsevier B.V.

Multimodal effective connectivity analysis reveals seizure focus and propagation in musicogenic epilepsy.

PubMed

Klamer, Silke; Rona, Sabine; Elshahabi, Adham; Lerche, Holger; Braun, Christoph; Honegger, Jürgen; Erb, Michael; Focke, Niels K

2015-06-01

Dynamic causal modeling (DCM) is a method to non-invasively assess effective connectivity between brain regions. 'Musicogenic epilepsy' is a rare reflex epilepsy syndrome in which seizures can be elicited by musical stimuli and thus represents a unique possibility to investigate complex human brain networks and test connectivity analysis tools. We investigated effective connectivity in a case of musicogenic epilepsy using DCM for fMRI, high-density (hd-) EEG and MEG and validated results with intracranial EEG recordings. A patient with musicogenic seizures was examined using hd-EEG/fMRI and simultaneous '256-channel hd-EEG'/'whole head MEG' to characterize the epileptogenic focus and propagation effects using source analysis techniques and DCM. Results were validated with invasive EEG recordings. We recorded one seizure with hd-EEG/fMRI and four auras with hd-EEG/MEG. During the seizures, increases of activity could be observed in the right mesial temporal region as well as bilateral mesial frontal regions. Effective connectivity analysis of fMRI and hd-EEG/MEG indicated that right mesial temporal neuronal activity drives changes in the frontal areas consistently in all three modalities, which was confirmed by the results of invasive EEG recordings. Seizures thus seem to originate in the right mesial temporal lobe and propagate to mesial frontal regions. Using DCM for fMRI, hd-EEG and MEG we were able to correctly localize focus and propagation of epileptic activity and thereby characterize the underlying epileptic network in a patient with musicogenic epilepsy. The concordance between all three functional modalities validated by invasive monitoring is noteworthy, both for epileptic activity spread as well as for effective connectivity analysis in general. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset.

PubMed

Bulgarelli, Chiara; Blasi, Anna; Arridge, Simon; Powell, Samuel; de Klerk, Carina C J M; Southgate, Victoria; Brigadoi, Sabrina; Penny, William; Tak, Sungho; Hamilton, Antonia

2018-04-12

Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies. fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data. This work opens new avenues for future research on effective connectivity in infancy by contributing a data analysis pipeline and guidance for applying DCM to infant fNIRS data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an `interface' nucleus

PubMed Central

Pawlisch, Benjamin A.; Remage-Healey, Luke

2014-01-01

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher-order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity. PMID:25453773

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus.

PubMed

Pawlisch, B A; Remage-Healey, L

2015-01-22

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Four-dimensional optoacoustic temperature mapping in laser-induced thermotherapy

NASA Astrophysics Data System (ADS)

Oyaga Landa, Francisco Javier; Deán-Ben, Xosé Luís.; Sroka, Ronald; Razansky, Daniel

2018-02-01

Photoablative laser therapy is in common use for selective destruction of malignant masses, vascular and brain abnormalities. Tissue ablation and coagulation are irreversible processes occurring shortly after crossing a certain thermal exposure threshold. As a result, accurate mapping of the temperature field is essential for optimizing the outcome of these clinical interventions. Here we demonstrate four-dimensional optoacoustic temperature mapping of the entire photoablated region. Accuracy of the method is investigated in tissue-mimicking phantom experiments. Deviations of the volumetric optoacoustic temperature readings provided at 40ms intervals remained below 10% for temperature elevations above 3°C, as validated by simultaneous thermocouple measurements. The excellent spatio-temporal resolution of the new temperature monitoring approach aims at improving safety and efficacy of laser-based photothermal procedures.

Neuronix enables continuous, simultaneous neural recording and electrical microstimulation.

PubMed

Zhi Yang; Jian Xu; Anh Tuan Nguyen; Tong Wu; Wenfeng Zhao; Wing-Kin Tam

2016-08-01

This paper reports a novel neurotechnology (Neuronix) and its validation through experiments. It is a miniature system-on-chip (SoC) that allows recording with simultaneous electrical microstimulation. This function has not been demonstrated before and enables precise, closed-loop neuromodulation. Neuronix represents recent advancement in brain technology and applies to both animal research and clinical applications.

Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

PubMed Central

Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

2012-01-01

Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

NASA Astrophysics Data System (ADS)

Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

2014-03-01

The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

Simultaneous measurement of glucose blood-brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS.

PubMed

Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

2012-09-01

Cerebral glucose consumption and glucose transport across the blood-brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMR(glc)) and glucose transport constants (K(T): half-saturation constant; T(max): maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMR(glc), K(T), and T(max) via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo (1)H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMR(glc), T(max), and K(T) were determined to be 0.44 ± 0.17 μmol/g per minute, 1.35 ± 0.47 μmol/g per minute, and 13.4 ± 6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMR(glc) and T(max) are more reliable than that of K(T). The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application.

An Examination of Dynamic Gene Expression Changes in the Mouse Brain During Pregnancy and the Postpartum Period.

PubMed

Ray, Surjyendu; Tzeng, Ruei-Ying; DiCarlo, Lisa M; Bundy, Joseph L; Vied, Cynthia; Tyson, Gary; Nowakowski, Richard; Arbeitman, Michelle N

2015-11-23

The developmental transition to motherhood requires gene expression changes that alter the brain to drive the female to perform maternal behaviors. We broadly examined the global transcriptional response in the mouse maternal brain, by examining four brain regions: hypothalamus, hippocampus, neocortex, and cerebellum, in virgin females, two pregnancy time points, and three postpartum time points. We find that overall there are hundreds of differentially expressed genes, but each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions. Interestingly, a set of "early-response genes" is repressed in all brain regions during pregnancy and postpartum stages. Several genes previously implicated in underlying postpartum depression change expression. This study serves as an atlas of gene expression changes in the maternal brain, with the results demonstrating that pregnancy, parturition, and postpartum maternal experience substantially impact diverse brain regions. Copyright © 2016 Ray et al.

Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, G.J.; Volkow, N.D.; Lau, Y.H.

1994-05-01

This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions ofmore » interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.« less

A generative model for segmentation of tumor and organs-at-risk for radiation therapy planning of glioblastoma patients

NASA Astrophysics Data System (ADS)

Agn, Mikael; Law, Ian; Munck af Rosenschöld, Per; Van Leemput, Koen

2016-03-01

We present a fully automated generative method for simultaneous brain tumor and organs-at-risk segmentation in multi-modal magnetic resonance images. The method combines an existing whole-brain segmentation technique with a spatial tumor prior, which uses convolutional restricted Boltzmann machines to model tumor shape. The method is not tuned to any specific imaging protocol and can simultaneously segment the gross tumor volume, peritumoral edema and healthy tissue structures relevant for radiotherapy planning. We validate the method on a manually delineated clinical data set of glioblastoma patients by comparing segmentations of gross tumor volume, brainstem and hippocampus. The preliminary results demonstrate the feasibility of the method.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Intraoperative brain hemodynamic response assessment with real-time hyperspectral optical imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Laurence, Audrey; Pichette, Julien; Angulo-Rodríguez, Leticia M.; Saint Pierre, Catherine; Lesage, Frédéric; Bouthillier, Alain; Nguyen, Dang Khoa; Leblond, Frédéric

2016-03-01

Following normal neuronal activity, there is an increase in cerebral blood flow and cerebral blood volume to provide oxygenated hemoglobin to active neurons. For abnormal activity such as epileptiform discharges, this hemodynamic response may be inadequate to meet the high metabolic demands. To verify this hypothesis, we developed a novel hyperspectral imaging system able to monitor real-time cortical hemodynamic changes during brain surgery. The imaging system is directly integrated into a surgical microscope, using the white-light source for illumination. A snapshot hyperspectral camera is used for detection (4x4 mosaic filter array detecting 16 wavelengths simultaneously). We present calibration experiments where phantoms made of intralipid and food dyes were imaged. Relative concentrations of three dyes were recovered at a video rate of 30 frames per second. We also present hyperspectral recordings during brain surgery of epileptic patients with concurrent electrocorticography recordings. Relative concentration maps of oxygenated and deoxygenated hemoglobin were extracted from the data, allowing real-time studies of hemodynamic changes with a good spatial resolution. Finally, we present preliminary results on phantoms obtained with an integrated spatial frequency domain imaging system to recover tissue optical properties. This additional module, used together with the hyperspectral imaging system, will allow quantification of hemoglobin concentrations maps. Our hyperspectral imaging system offers a new tool to analyze hemodynamic changes, especially in the case of epileptiform discharges. It also offers an opportunity to study brain connectivity by analyzing correlations between hemodynamic responses of different tissue regions.

Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks.

PubMed

Calhoun, Vince D; Kiehl, Kent A; Pearlson, Godfrey D

2008-07-01

Brain regions which exhibit temporally coherent fluctuations, have been increasingly studied using functional magnetic resonance imaging (fMRI). Such networks are often identified in the context of an fMRI scan collected during rest (and thus are called "resting state networks"); however, they are also present during (and modulated by) the performance of a cognitive task. In this article, we will refer to such networks as temporally coherent networks (TCNs). Although there is still some debate over the physiological source of these fluctuations, TCNs are being studied in a variety of ways. Recent studies have examined ways TCNs can be used to identify patterns associated with various brain disorders (e.g. schizophrenia, autism or Alzheimer's disease). Independent component analysis (ICA) is one method being used to identify TCNs. ICA is a data driven approach which is especially useful for decomposing activation during complex cognitive tasks where multiple operations occur simultaneously. In this article we review recent TCN studies with emphasis on those that use ICA. We also present new results showing that TCNs are robust, and can be consistently identified at rest and during performance of a cognitive task in healthy individuals and in patients with schizophrenia. In addition, multiple TCNs show temporal and spatial modulation during the cognitive task versus rest. In summary, TCNs show considerable promise as potential imaging biological markers of brain diseases, though each network needs to be studied in more detail. (c) 2008 Wiley-Liss, Inc.

Modulation of Temporally Coherent Brain Networks Estimated Using ICA at Rest and During Cognitive Tasks

PubMed Central

Calhoun, Vince D.; Kiehl, Kent A.; Pearlson, Godfrey D.

2009-01-01

Brain regions which exhibit temporally coherent fluctuations, have been increasingly studied using functional magnetic resonance imaging (fMRI). Such networks are often identified in the context of an fMRI scan collected during rest (and thus are called “resting state networks”); however, they are also present during (and modulated by) the performance of a cognitive task. In this article, we will refer to such networks as temporally coherent networks (TCNs). Although there is still some debate over the physiological source of these fluctuations, TCNs are being studied in a variety of ways. Recent studies have examined ways TCNs can be used to identify patterns associated with various brain disorders (e.g. schizophrenia, autism or Alzheimer’s disease). Independent component analysis (ICA) is one method being used to identify TCNs. ICA is a data driven approach which is especially useful for decomposing activation during complex cognitive tasks where multiple operations occur simultaneously. In this article we review recent TCN studies with emphasis on those that use ICA. We also present new results showing that TCNs are robust, and can be consistently identified at rest and during performance of a cognitive task in healthy individuals and in patients with schizophrenia. In addition, multiple TCNs show temporal and spatial modulation during the cognitive task versus rest. In summary, TCNs show considerable promise as potential imaging biological markers of brain diseases, though each network needs to be studied in more detail. PMID:18438867

Spirulina platensis attenuates the associated neurobehavioral and inflammatory response impairments in rats exposed to lead acetate.

PubMed

Khalil, Samah R; Khalifa, Hesham A; Abdel-Motal, Sabry M; Mohammed, Hesham H; Elewa, Yaser H A; Mahmoud, Hend Atta

2018-08-15

Heavy metals are well known as environmental pollutants with hazardous impacts on human and animal health because of their wide industrial usage. In the present study, the role of Spirulina platensis in reversing the oxidative stress-mediated brain injury elicited by lead acetate exposure was evaluated. In order to accomplish this aim, rats were orally administered with 300 mg/kg bw Spirulina for 15 d, before and simultaneously with an intraperitoneal injection of 50 mg/kg bw lead acetate [6 injections through the two weeks]. As a result, the co-administration of Spirulina with lead acetate reversed the most impaired open field behavioral indices; however, this did not happen for swimming performance, inclined plane, and grip strength tests. In addition, it was observed that Spirulina diminished the lead content that accumulated in both the blood and the brain tissue of the exposed rats, and reduced the elevated levels of oxidative damage indices, and brain proinflammatory markers. Also, because of the Spirulina administration, the levels of the depleted biomarkers of antioxidant status and interleukin-10 in the lead-exposed rats were improved. Moreover, Spirulina protected the brain tissue (cerebrum and cerebellum) against the changes elicited by lead exposure, and also decreased the reactivity of HSP70 and Caspase-3 in both cerebrum and cerebellum tissues. Collectively, our findings demonstrate that Spirulina has a potential use as a food supplement in the regions highly polluted with heavy metals. Copyright © 2018 Elsevier Inc. All rights reserved.

Altered Brain Microstate Dynamics in Adolescents with Narcolepsy

PubMed Central

Drissi, Natasha M.; Szakács, Attila; Witt, Suzanne T.; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

2016-01-01

Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13–20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

Brain regions involved in observing and trying to interpret dog behaviour.

PubMed

Desmet, Charlotte; van der Wiel, Alko; Brass, Marcel

2017-01-01

Humans and dogs have interacted for millennia. As a result, humans (and especially dog owners) sometimes try to interpret dog behaviour. While there is extensive research on the brain regions that are involved in mentalizing about other peoples' behaviour, surprisingly little is known of whether we use these same brain regions to mentalize about animal behaviour. In this fMRI study we investigate whether brain regions involved in mentalizing about human behaviour are also engaged when observing dog behaviour. Here we show that these brain regions are more engaged when observing dog behaviour that is difficult to interpret compared to dog behaviour that is easy to interpret. Interestingly, these results were not only obtained when participants were instructed to infer reasons for the behaviour but also when they passively viewed the behaviour, indicating that these brain regions are activated by spontaneous mentalizing processes.

Brain regions involved in observing and trying to interpret dog behaviour

PubMed Central

Desmet, Charlotte; van der Wiel, Alko; Brass, Marcel

2017-01-01

Humans and dogs have interacted for millennia. As a result, humans (and especially dog owners) sometimes try to interpret dog behaviour. While there is extensive research on the brain regions that are involved in mentalizing about other peoples’ behaviour, surprisingly little is known of whether we use these same brain regions to mentalize about animal behaviour. In this fMRI study we investigate whether brain regions involved in mentalizing about human behaviour are also engaged when observing dog behaviour. Here we show that these brain regions are more engaged when observing dog behaviour that is difficult to interpret compared to dog behaviour that is easy to interpret. Interestingly, these results were not only obtained when participants were instructed to infer reasons for the behaviour but also when they passively viewed the behaviour, indicating that these brain regions are activated by spontaneous mentalizing processes. PMID:28931030

On Expression Patterns and Developmental Origin of Human Brain Regions.

PubMed

Kirsch, Lior; Chechik, Gal

2016-08-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

On Expression Patterns and Developmental Origin of Human Brain Regions

PubMed Central

Kirsch, Lior; Chechik, Gal

2016-01-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex

PubMed Central

van Kerkoerle, Timo; Self, Matthew W.; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R.

2014-01-01

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition. PMID:25205811

State Space Modeling of Time-Varying Contemporaneous and Lagged Relations in Connectivity Maps

PubMed Central

Molenaar, Peter C. M.; Beltz, Adriene M.; Gates, Kathleen M.; Wilson, Stephen J.

2017-01-01

Most connectivity mapping techniques for neuroimaging data assume stationarity (i.e., network parameters are constant across time), but this assumption does not always hold true. The authors provide a description of a new approach for simultaneously detecting time-varying (or dynamic) contemporaneous and lagged relations in brain connectivity maps. Specifically, they use a novel raw data likelihood estimation technique (involving a second-order extended Kalman filter/smoother embedded in a nonlinear optimizer) to determine the variances of the random walks associated with state space model parameters and their autoregressive components. The authors illustrate their approach with simulated and blood oxygen level-dependent functional magnetic resonance imaging data from 30 daily cigarette smokers performing a verbal working memory task, focusing on seven regions of interest (ROIs). Twelve participants had dynamic directed functional connectivity maps: Eleven had one or more time-varying contemporaneous ROI state loadings, and one had a time-varying autoregressive parameter. Compared to smokers without dynamic maps, smokers with dynamic maps performed the task with greater accuracy. Thus, accurate detection of dynamic brain processes is meaningfully related to behavior in a clinical sample. PMID:26546863

Modeling of cortical signals using echo state networks

NASA Astrophysics Data System (ADS)

Zhou, Hanying; Wang, Yongji; Huang, Jiangshuai

2009-10-01

Diverse modeling frameworks have been utilized with the ultimate goal of translating brain cortical signals into prediction of visible behavior. The inputs to these models are usually multidimensional neural recordings collected from relevant regions of a monkey's brain while the outputs are the associated behavior which is typically the 2-D or 3-D hand position of a primate. Here our task is to set up a proper model in order to figure out the move trajectories by input the neural signals which are simultaneously collected in the experiment. In this paper, we propose to use Echo State Networks (ESN) to map the neural firing activities into hand positions. ESN is a newly developed recurrent neural network(RNN) model. Besides its dynamic property and short term memory just as other recurrent neural networks have, it has a special echo state property which endows it with the ability to model nonlinear dynamic systems powerfully. What distinguished it from transitional recurrent neural networks most significantly is its special learning method. In this paper we train this net with a refined version of its typical training method and get a better model.

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

PubMed

van Kerkoerle, Timo; Self, Matthew W; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R

2014-10-07

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson's disease.

PubMed

Luoma, Jarkko; Pekkonen, Eero; Airaksinen, Katja; Helle, Liisa; Nurminen, Jussi; Taulu, Samu; Mäkelä, Jyrki P

2018-06-22

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD. Copyright © 2018. Published by Elsevier B.V.

Investigation of brain structure in the 1-month infant.

PubMed

Dean, Douglas C; Planalp, E M; Wooten, W; Schmidt, C K; Kecskemeti, S R; Frye, C; Schmidt, N L; Goldsmith, H H; Alexander, A L; Davidson, R J

2018-05-01

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

PubMed

Banerjee, Soumyabrata; Poddar, Mrinal K

2015-03-01

Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Brain signal complexity rises with repetition suppression in visual learning.

PubMed

Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

2016-06-21

Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual areas. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Regional differences in brain glucose metabolism determined by imaging mass spectrometry.

PubMed

Kleinridders, André; Ferris, Heather A; Reyzer, Michelle L; Rath, Michaela; Soto, Marion; Manier, M Lisa; Spraggins, Jeffrey; Yang, Zhihong; Stanton, Robert C; Caprioli, Richard M; Kahn, C Ronald

2018-06-01

Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). To examine the relative abundance of glucose and other metabolites in the brain, mouse brain sections were subjected to imaging mass spectrometry at a resolution of 100 μm. This was correlated with immunohistochemistry, qPCR, western blotting and enzyme assays of dissected brain regions to determine the relative contributions of the glycolytic and pentose phosphate pathways to regional glucose metabolism. In brain, there are significant regional differences in glucose metabolism, with low levels of hexose bisphosphate (a glycolytic intermediate) and high levels of the pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolite hexose phosphate in thalamus compared to cortex. The ratio of ATP to ADP is significantly higher in white matter tracts, such as corpus callosum, compared to less myelinated areas. While the brain is able to maintain normal ratios of hexose phosphate, hexose bisphosphate, ATP, and ADP during fasting, fasting causes a large increase in cortical and hippocampal lactate. These data demonstrate the importance of direct measurement of metabolic intermediates to determine regional differences in brain glucose metabolism and illustrate the strength of imaging mass spectrometry for investigating the impact of changing metabolic states on brain function at a regional level with high resolution. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Identification of a set of genes showing regionally enriched expression in the mouse brain

PubMed Central

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

2008-01-01

Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

Identification of a set of genes showing regionally enriched expression in the mouse brain.

PubMed

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa L C; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven J M

2008-07-14

The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia.

PubMed

Alloza, Clara; Cox, Simon R; Duff, Barbara; Semple, Scott I; Bastin, Mark E; Whalley, Heather C; Lawrie, Stephen M

2016-08-30

Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Developmental Reorganization of the Core and Extended Face Networks Revealed by Global Functional Connectivity.

PubMed

Wang, Xu; Zhu, Qi; Song, Yiying; Liu, Jia

2017-08-28

Prior studies on development of functional specialization in human brain mainly focus on age-related increases in regional activation and connectivity among regions. However, a few recent studies on the face network demonstrate age-related decrease in face-specialized activation in the extended face network (EFN), in addition to increase in activation in the core face network (CFN). Here we used a voxel-based global brain connectivity approach to investigate whether development of the face network exhibited both increase and decrease in network connectivity. We found the voxel-wise resting-state functional connectivity (FC) within the CFN increased with age in bilateral posterior superior temporal sulcus, suggesting the integration of the CFN during development. Interestingly, the FC of the voxels in the EFN to the right fusiform face area and occipital face area decreased with age, suggesting that the CFN segregated from the EFN during development. Moreover, the age-related connectivity in the CFN was related to behavioral performance in face processing. Overall, our study demonstrated developmental reorganization of the face network achieved by both integration within the CFN and segregation of the CFN from the EFN, which may account for the simultaneous increases and decreases in neural activation during the development of the face network. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Joint brain connectivity estimation from diffusion and functional MRI data

NASA Astrophysics Data System (ADS)

Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

2015-03-01

Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information flow is introduced and used to model the propagation of information between GM areas through WM fiber bundles. The link capacity, i.e., ability to transfer information, is characterized by the relative strength of fiber bundles, e.g., fiber count gathered from the tractography of dMRI data. The node information demand is considered to be proportional to the correlation between neural activity at various cortical areas involved in a particular functional mode (e.g. visual, motor, etc.). These two properties lead to the link capacity and node demand constraints in the proposed model. Moreover, the information flow of a link cannot exceed the demand from either end node. This is captured by the feasibility constraints. Two different cost functions are considered in the optimization formulation in this paper. The first cost function, the reciprocal of fiber strength represents the unit cost for information passing through the link. In the second cost function, a min-max (minimizing the maximal link load) approach is used to balance the usage of each link. Optimizing the first cost function selects the pathway with strongest fiber strength for information propagation. In the second case, the optimization procedure finds all the possible propagation pathways and allocates the flow proportionally to their strength. Additionally, a penalty term is incorporated with both the cost functions to capture the possible missing and weak anatomical connections. With this set of constraints and the proposed cost functions, solving the network optimization problem recovers missing and weak anatomical connections supported by the functional information and provides the functional-associated anatomical subnetworks. Feasibility is demonstrated using realistic diffusion and functional MRI phantom data. It is shown that the proposed model recovers the maximum number of true connections, with fewest number of false connections when compared with the connectivity derived from a joint probabilistic model using the expectation-maximization (EM) algorithm presented in a prior work. We also apply the proposed method to data provided by the Human Connectome Project (HCP).

Down syndrome's brain dynamics: analysis of fractality in resting state.

PubMed

Hemmati, Sahel; Ahmadlou, Mehran; Gharib, Masoud; Vameghi, Roshanak; Sajedi, Firoozeh

2013-08-01

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.

Functional neuroimaging: technical, logical, and social perspectives.

PubMed

Aguirre, Geoffrey K

2014-01-01

Neuroscientists have long sought to study the dynamic activity of the human brain-what's happening in the brain, that is, while people are thinking, feeling, and acting. Ideally, an inside look at brain function would simultaneously and continuously measure the biochemical state of every cell in the central nervous system. While such a miraculous method is science fiction, a century of progress in neuroimaging technologies has made such simultaneous and continuous measurement a plausible fiction. Despite this progress, practitioners of modern neuroimaging struggle with two kinds of limitations: those that attend the particular neuroimaging methods we have today and those that would limit any method of imaging neural activity, no matter how powerful. In this essay, I consider the liabilities and potential of techniques that measure human brain activity. I am concerned here only with methods that measure relevant physiologic states of the central nervous system and relate those measures to particular mental states. I will consider in particular the preeminent method of functional neuroimaging: BOLD fMRI. While there are several practical limits on the biological information that current technologies can measure, these limits-as important as they are-are minor in comparison to the fundamental logical restraints on the conclusions that can be drawn from brain imaging studies. © 2014 by The Hastings Center.

Differential temporal control of Foxa.a and Zic-r.b specifies brain versus notochord fate in the ascidian embryo.

PubMed

Ikeda, Tatsuro; Satou, Yutaka

2017-01-01

In embryos of an invertebrate chordate, Ciona intestinalis, two transcription factors, Foxa.a and Zic-r.b, are required for specification of the brain and the notochord, which are derived from distinct cell lineages. In the brain lineage, Foxa.a and Zic-r.b are expressed with no temporal overlap. In the notochord lineage, Foxa.a and Zic-r.b are expressed simultaneously. In the present study, we found that the temporally non-overlapping expression of Foxa.a and Zic-r.b in the brain lineage was regulated by three repressors: Prdm1-r.a (formerly called BZ1), Prdm1-r.b (BZ2) and Hes.a. In morphant embryos of these three repressor genes, Foxa.a expression was not terminated at the normal time, and Zic-r.b was precociously expressed. Consequently, Foxa.a and Zic-r.b were expressed simultaneously, which led to ectopic activation of Brachyury and its downstream pathways for notochord differentiation. Thus, temporal controls by transcriptional repressors are essential for specification of the two distinct fates of brain and notochord by Foxa.a and Zic-r.b Such a mechanism might enable the repeated use of a limited repertoire of transcription factors in developmental gene regulatory networks. © 2017. Published by The Company of Biologists Ltd.

Taurine as osmoregulator and neuromodulator in the brain.

PubMed

Oja, S S; Saransaari, P

1996-06-01

Taurine has been assumed to function as an osmoregulator and neuromodulator in the brain. The pertinent studies are now reviewed in an attempt to formulate a unifying hypothesis as to how taurine could simultaneously act in both roles. Neuromodulatory actions of taurine may also underlie its protective effects against neuronal overexcitation and glutamate agonist-induced neurotoxicity.

The Teaching and the Learning Brain: A Cortical Hemodynamic Marker of Teacher-Student Interactions in the Socratic Dialog

ERIC Educational Resources Information Center

Holper, Lisa; Goldin, Andrea P.; Shalom, Diego E.; Battro, Antonio M.; Wolf, Martin; Sigman, Mariano

2013-01-01

The study aimed to step into two-person (teacher-student) educational neuroscience. We describe a physiological marker of cortical hemodynamic correlates involved in teacher-student interactions during performance of a classical teaching model, the Socratic dialog. We recorded prefrontal brain activity during dialog execution simultaneously in…

Changing Their Minds

ERIC Educational Resources Information Center

Belnomi, Cynthia

2015-01-01

Whenever the author explains the brain to her second-grade students, the look on their faces is one of simultaneous fascination and relief. What caught her off guard was the relief. In retrospect, it makes pure sense. Of course it was a relief for them to realize that they could affect their brains and its abilities--that nothing was set in stone.…

PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB.

PubMed

Faria, Daniele de Paula; Copray, Sjef; Sijbesma, Jurgen W A; Willemsen, Antoon T M; Buchpiguel, Carlos A; Dierckx, Rudi A J O; de Vries, Erik F J

2014-05-01

In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [(11)C]CIC make this tracer less suitable for in vivo PET imaging. [(11)C]PIB showed good uptake in the white matter in the cerebrum, but [(11)C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [(11)C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [(11)C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [(11)C]CIC and [(11)C]PIB.

Opposing effects of dopamine antagonism in a motor sequence task—tiapride increases cortical excitability and impairs motor learning

PubMed Central

Lissek, Silke; Vallana, Guido S.; Schlaffke, Lara; Lenz, Melanie; Dinse, Hubert R.; Tegenthoff, Martin

2014-01-01

The dopaminergic system is involved in learning and participates in the modulation of cortical excitability (CE). CE has been suggested as a marker of learning and use-dependent plasticity. However, results from separate studies on either motor CE or motor learning challenge this notion, suggesting opposing effects of dopaminergic modulation upon these parameters: while agonists decrease and antagonists increase CE, motor learning is enhanced by agonists and disturbed by antagonists. To examine whether this discrepancy persists when complex motor learning and motor CE are measured in the same experimental setup, we investigated the effects of dopaminergic (DA) antagonism upon both parameters and upon task-associated brain activation. Our results demonstrate that DA-antagonism has opposing effects upon motor CE and motor sequence learning. Tiapride did not alter baseline CE, but increased CE post training of a complex motor sequence while simultaneously impairing motor learning. Moreover, tiapride reduced activation in several brain regions associated with motor sequence performance, i.e., dorsolateral PFC (dlPFC), supplementary motor area (SMA), Broca's area, cingulate and caudate body. Blood-oxygenation-level-dependent (BOLD) intensity in anterior cingulate and caudate body, but not CE, correlated with performance across groups. In summary, our results do not support a concept of CE as a general marker of motor learning, since they demonstrate that a straightforward relation of increased CE and higher learning success does not apply to all instances of motor learning. At least for complex motor tasks that recruit a network of brain regions outside motor cortex, CE in primary motor cortex is probably no central determinant for learning success. PMID:24994972

A neural circuit covarying with social hierarchy in macaques.

PubMed

Noonan, MaryAnn P; Sallet, Jerome; Mars, Rogier B; Neubert, Franz X; O'Reilly, Jill X; Andersson, Jesper L; Mitchell, Anna S; Bell, Andrew H; Miller, Karla L; Rushworth, Matthew F S

2014-09-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

Functionally independent components of the late positive event-related potential during visual spatial attention.

PubMed

Makeig, S; Westerfield, M; Jung, T P; Covington, J; Townsend, J; Sejnowski, T J; Courchesne, E

1999-04-01

Human event-related potentials (ERPs) were recorded from 10 subjects presented with visual target and nontarget stimuli at five screen locations and responding to targets presented at one of the locations. The late positive response complexes of 25-75 ERP average waveforms from the two task conditions were simultaneously analyzed with Independent Component Analysis, a new computational method for blindly separating linearly mixed signals. Three spatially fixed, temporally independent, behaviorally relevant, and physiologically plausible components were identified without reference to peaks in single-channel waveforms. A novel frontoparietal component (P3f) began at approximately 140 msec and peaked, in faster responders, at the onset of the motor command. The scalp distribution of P3f appeared consistent with brain regions activated during spatial orienting in functional imaging experiments. A longer-latency large component (P3b), positive over parietal cortex, was followed by a postmotor potential (Pmp) component that peaked 200 msec after the button press and reversed polarity near the central sulcus. A fourth component associated with a left frontocentral nontarget positivity (Pnt) was evoked primarily by target-like distractors presented in the attended location. When no distractors were presented, responses of five faster-responding subjects contained largest P3f and smallest Pmp components; when distractors were included, a Pmp component appeared only in responses of the five slower-responding subjects. Direct relationships between component amplitudes, latencies, and behavioral responses, plus similarities between component scalp distributions and regional activations reported in functional brain imaging experiments suggest that P3f, Pmp, and Pnt measure the time course and strength of functionally distinct brain processes.

A Neural Circuit Covarying with Social Hierarchy in Macaques

PubMed Central

Neubert, Franz X.; O'Reilly, Jill X.; Andersson, Jesper L.; Mitchell, Anna S.; Bell, Andrew H.; Miller, Karla L.; Rushworth, Matthew F. S.

2014-01-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status. PMID:25180883

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

Analyzing and Assessing Brain Structure with Graph Connectivity Measures

DTIC Science & Technology

2014-05-09

structural brain networks, i.e. determining which regions of the brain are physically connected. Meanwhile, functional MRI ( fMRI ) yields an image of...produced by fMRI is a map of which parts are of the brain are active and which are not at a given time. In creating functional networks, regions of...the brain which often activitate together, i.e., often show up on fMRI as deoxygenated regions together, are considered connected. DTI allows the

Understanding brain networks and brain organization

PubMed Central

Pessoa, Luiz

2014-01-01

What is the relationship between brain and behavior? The answer to this question necessitates characterizing the mapping between structure and function. The aim of this paper is to discuss broad issues surrounding the link between structure and function in the brain that will motivate a network perspective to understanding this question. As others in the past, I argue that a network perspective should supplant the common strategy of understanding the brain in terms of individual regions. Whereas this perspective is needed for a fuller characterization of the mind-brain, it should not be viewed as panacea. For one, the challenges posed by the many-to-many mapping between regions and functions is not dissolved by the network perspective. Although the problem is ameliorated, one should not anticipate a one-to-one mapping when the network approach is adopted. Furthermore, decomposition of the brain network in terms of meaningful clusters of regions, such as the ones generated by community-finding algorithms, does not by itself reveal “true” subnetworks. Given the hierarchical and multi-relational relationship between regions, multiple decompositions will offer different “slices” of a broader landscape of networks within the brain. Finally, I described how the function of brain regions can be characterized in a multidimensional manner via the idea of diversity profiles. The concept can also be used to describe the way different brain regions participate in networks. PMID:24819881

Localized Fluctuant Oscillatory Activity by Working Memory Load: A Simultaneous EEG-fMRI Study.

PubMed

Zhao, Xiaojie; Li, Xiaoyun; Yao, Li

2017-01-01

Working memory (WM) is a resource-limited memory system for temporary storage and processing of brain information during the execution of cognitive tasks. Increased WM load will increase the amount and difficulty of memory information. Several studies have used electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) to explore load-dependent cognition processing according to the time courses of electrophysiological activity or the spatial pattern of blood oxygen metabolic activity. However, the relationships between these two activities and the underlying neural mechanism are still unclear. In this study, using simultaneously collected EEG and fMRI data under an n-back verbal WM task, we modeled the spectral perturbation of EEG oscillation and fMRI activation through joint independent component analysis (JICA). Multi-channel oscillation features were also introduced into the JICA model for further analysis. The results showed that time-locked activity of theta and beta were modulated by memory load in the early stimuli evaluation stage, corresponding to the enhanced activation in the frontal and parietal lobe, which were involved in stimulus discrimination, information encoding and delay-period activity. In the late response selection stage, alpha and gamma activity changes dependent on the load correspond to enhanced activation in the areas of frontal, temporal and parietal lobes, which played important roles in attention, information extraction and memory retention. These findings suggest that the increases in memory load not only affect the intensity and time course of the EEG activities, but also lead to the enhanced activation of brain regions which plays different roles during different time periods of cognitive process of WM.

Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-01-01

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

Structural connectivity asymmetry in the neonatal brain.

PubMed

Ratnarajah, Nagulan; Rifkin-Graboi, Anne; Fortier, Marielle V; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

2013-07-15

Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-world characteristics were exhibited, but did not differ between the two hemispheres, suggesting that neighboring brain regions connect tightly with each other, and that one region is only a few paths away from any other region within each hemisphere. Moreover, the neonatal brain showed greater structural efficiency in the left hemisphere than that in the right. In neonates, brain regions involved in motor, language, and memory functions play crucial roles in efficient communication in the left hemisphere, while brain regions involved in emotional processes play crucial roles in efficient communication in the right hemisphere. These findings suggest that even at birth, the topology of each cerebral hemisphere is organized in an efficient and compact manner that maps onto asymmetric functional specializations seen in adults, implying lateralized brain functions in infancy. Copyright © 2013 Elsevier Inc. All rights reserved.

Dynamic functional brain networks involved in simple visual discrimination learning.

PubMed

Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis

2014-10-01

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Coherent activity between brain regions that code for value is linked to the malleability of human behavior

PubMed Central

Cooper, Nicole; Bassett, Danielle S.; Falk, Emily B.

2017-01-01

Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave. PMID:28240271

Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

NASA Astrophysics Data System (ADS)

Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

2017-04-01

Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

Age-and Brain Region-Specific Differences in Mitochondrial ...

EPA Pesticide Factsheets

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

Hyperacute Simultaneous Cardiocerebral Infarction: Rescuing the Brain or the Heart First?

PubMed

Kijpaisalratana, Naruchorn; Chutinet, Aurauma; Suwanwela, Nijasri C

2017-01-01

Concurrent acute ischemic stroke and acute myocardial infarction is an uncommon medical emergency condition. The challenge for the physicians regarding the management of this situation is paramount since early management of one condition will inevitably delay the other. We present two illustrative cases of "hyperacute simultaneous cardiocerebral infarction" who presented with simultaneous cardiocerebral infarction and arrived at the hospital within the thrombolytic therapeutic window for acute ischemic stroke of 4.5 h. We propose an algorithm for managing the patient with hyperacute simultaneous cardiocerebral infarction based on hemodynamic status and suggest close cardiac monitoring based on the site of cerebral infarction.

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

Design of a fused phantom for quantitative evaluation of brain metabolites and enhanced quality assurance testing for magnetic resonance imaging and spectroscopy.

PubMed

Song, Kyu-Ho; Kim, Sang-Young; Lee, Do-Wan; Jung, Jin-Young; Lee, Jung-Hoon; Baek, Hyeon-Man; Choe, Bo-Young

2015-11-30

Magnetic resonance imaging and spectroscopy (MRI-MRS) is a useful tool for the identification and evaluation of chemical changes in anatomical regions. Quality assurance (QA) is performed in either images or spectra using QA phantom. Therefore, consistent and uniform technical MRI-MRS QA is crucial. Here we developed an MRI-MRS fused phantom along with the inserts for metabolite quantification to simultaneously optimize QA parameters for both MRI and MRS. T1- and T2-weighted images were obtained and MRS was performed with point-resolved spectroscopy. Using the fused phantom, the results of measuring MRI factors were: geometric distortion, <2% and ± 2 mm; image intensity uniformity, 83.09 ± 1.33%; percent-signal ghosting, 0.025 ± 0.004; low-contrast object detectability, 27.85 ± 0.80. In addition, the signal-to-noise ratio of N-acetyl-aspartate was consistently high (42.00 ± 5.66). In previous studies, MR phantoms could not obtain information from both images and spectra in the MR scanner simultaneously. Here we designed and developed a phantom for accurate and consistent QA within the acceptance range. It is important to take into account variations in the QA value using the MRI-MRS phantom, when comparing to other clinical or research MR scanners. The MRI-MRS QA factors obtained simultaneously using the phantom can facilitate evaluation of both images and spectra, and provide guidelines for obtaining MRI and MRS QA factors simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Next-generation in vivo optical imaging with short-wave infrared quantum dots.

PubMed

Bruns, Oliver T; Bischof, Thomas S; Harris, Daniel K; Franke, Daniel; Shi, Yanxiang; Riedemann, Lars; Bartelt, Alexander; Jaworski, Frank B; Carr, Jessica A; Rowlands, Christopher J; Wilson, Mark W B; Chen, Ou; Wei, He; Hwang, Gyu Weon; Montana, Daniel M; Coropceanu, Igor; Achorn, Odin B; Kloepper, Jonas; Heeren, Joerg; So, Peter T C; Fukumura, Dai; Jensen, Klavs F; Jain, Rakesh K; Bawendi, Moungi G

2017-01-01

For in vivo imaging, the short-wavelength infrared region (SWIR; 1000-2000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. Here, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots (QDs) that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. To demonstrate the unprecedented combination of deep penetration, high spatial resolution, multicolor imaging and fast-acquisition-speed afforded by the SWIR QDs, we quantified, in mice, the metabolic turnover rates of lipoproteins in several organs simultaneously and in real time as well as heartbeat and breathing rates in awake and unrestrained animals, and generated detailed three-dimensional quantitative flow maps of the mouse brain vasculature.

A common neural hub resolves syntactic and non-syntactic conflict through cooperation with task-specific networks

PubMed Central

Hsu, Nina S.; Jaeggi, Susanne M.; Novick, Jared M.

2017-01-01

Regions within the left inferior frontal gyrus (LIFG) have simultaneously been implicated in syntactic processing and cognitive control. Accounts attempting to unify LIFG’s function hypothesize that, during comprehension, cognitive control resolves conflict between incompatible representations of sentence meaning. Some studies demonstrate co-localized activity within LIFG for syntactic and non-syntactic conflict resolution, suggesting domain-generality, but others show non-overlapping activity, suggesting domain-specific cognitive control and/or regions that respond uniquely to syntax. We propose however that examining exclusive activation sites for certain contrasts creates a false dichotomy: both domain-general and domain-specific neural machinery must coordinate to facilitate conflict resolution across domains. Here, subjects completed four diverse tasks involving conflict —one syntactic, three non-syntactic— while undergoing fMRI. Though LIFG consistently activated within individuals during conflict processing, functional connectivity analyses revealed task-specific coordination with distinct brain networks. Thus, LIFG may function as a conflict-resolution “hub” that cooperates with specialized neural systems according to information content. PMID:28110105

Dynamic range adaptation in primary motor cortical populations

PubMed Central

Rasmussen, Robert G; Schwartz, Andrew; Chase, Steven M

2017-01-01

Neural populations from various sensory regions demonstrate dynamic range adaptation in response to changes in the statistical distribution of their input stimuli. These adaptations help optimize the transmission of information about sensory inputs. Here, we show a similar effect in the firing rates of primary motor cortical cells. We trained monkeys to operate a brain-computer interface in both two- and three-dimensional virtual environments. We found that neurons in primary motor cortex exhibited a change in the amplitude of their directional tuning curves between the two tasks. We then leveraged the simultaneous nature of the recordings to test several hypotheses about the population-based mechanisms driving these changes and found that the results are most consistent with dynamic range adaptation. Our results demonstrate that dynamic range adaptation is neither limited to sensory regions nor to rescaling of monotonic stimulus intensity tuning curves, but may rather represent a canonical feature of neural encoding. DOI: http://dx.doi.org/10.7554/eLife.21409.001 PMID:28417848

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

PubMed Central

Nayak, Prasunpriya; Chatterjee, Ajay K

2003-01-01

Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Postnatal brain development of the pulse type, weakly electric gymnotid fish Gymnotus omarorum.

PubMed

Iribarne, Leticia; Castelló, María E

2014-01-01

Teleosts are a numerous and diverse group of fish showing great variation in body shape, ecological niches and behaviors, and a correspondent diversity in brain morphology, usually associated with their functional specialization. Weakly electric fish are a paradigmatic example of functional specialization, as these teleosts use self-generated electric fields to sense the nearby environment and communicate with conspecifics, enabling fish to better exploit particular ecological niches. We analyzed the development of the brain of the pulse type gymnotid Gymnotus omarorum, focusing on the brain regions involved directly or indirectly in electrosensory information processing. A morphometric analysis has been made of the whole brain and of brain regions of interest, based on volumetric data obtained from 3-D reconstructions to study the growth of the whole brain and the relative growth of brain regions, from late larvae to adulthood. In the smallest studied larvae some components of the electrosensory pathway appeared to be already organized and functional, as evidenced by tract-tracing and in vivo field potential recordings of electrosensory-evoked activity. From late larval to adult stages, rombencephalic brain regions (cerebellum and electrosensory lateral line lobe) showed a positive allometric growth, mesencephalic brain regions showed a negative allometric growth, and the telencephalon showed an isometric growth. In a first step towards elucidating the role of cell proliferation in the relative growth of the analyzed brain regions, we also studied the spatial distribution of proliferation zones by means of pulse type BrdU labeling revealed by immunohistochemistry. The brain of G. omarorum late larvae showed a widespread distribution of proliferating zones, most of which were located at the ventricular-cisternal lining. Interestingly, we also found extra ventricular-cisternal proliferation zones at in the rombencephalic cerebellum and electrosensory lateral line lobe. We discuss the role of extraventricular-cisternal proliferation in the relative growth of the latter brain regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Categorization for Faces and Tools—Two Classes of Objects Shaped by Different Experience—Differs in Processing Timing, Brain Areas Involved, and Repetition Effects

PubMed Central

Kozunov, Vladimir; Nikolaeva, Anastasia; Stroganova, Tatiana A.

2018-01-01

The brain mechanisms that integrate the separate features of sensory input into a meaningful percept depend upon the prior experience of interaction with the object and differ between categories of objects. Recent studies using representational similarity analysis (RSA) have characterized either the spatial patterns of brain activity for different categories of objects or described how category structure in neuronal representations emerges in time, but never simultaneously. Here we applied a novel, region-based, multivariate pattern classification approach in combination with RSA to magnetoencephalography data to extract activity associated with qualitatively distinct processing stages of visual perception. We asked participants to name what they see whilst viewing bitonal visual stimuli of two categories predominantly shaped by either value-dependent or sensorimotor experience, namely faces and tools, and meaningless images. We aimed to disambiguate the spatiotemporal patterns of brain activity between the meaningful categories and determine which differences in their processing were attributable to either perceptual categorization per se, or later-stage mentalizing-related processes. We have extracted three stages of cortical activity corresponding to low-level processing, category-specific feature binding, and supra-categorical processing. All face-specific spatiotemporal patterns were associated with bilateral activation of ventral occipito-temporal areas during the feature binding stage at 140–170 ms. The tool-specific activity was found both within the categorization stage and in a later period not thought to be associated with binding processes. The tool-specific binding-related activity was detected within a 210–220 ms window and was located to the intraparietal sulcus of the left hemisphere. Brain activity common for both meaningful categories started at 250 ms and included widely distributed assemblies within parietal, temporal, and prefrontal regions. Furthermore, we hypothesized and tested whether activity within face and tool-specific binding-related patterns would demonstrate oppositely acting effects following procedural perceptual learning. We found that activity in the ventral, face-specific network increased following the stimuli repetition. In contrast, tool processing in the dorsal network adapted by reducing its activity over the repetition period. Altogether, we have demonstrated that activity associated with visual processing of faces and tools during the categorization stage differ in processing timing, brain areas involved, and in their dynamics underlying stimuli learning. PMID:29379426

Categorization for Faces and Tools-Two Classes of Objects Shaped by Different Experience-Differs in Processing Timing, Brain Areas Involved, and Repetition Effects.

PubMed

Kozunov, Vladimir; Nikolaeva, Anastasia; Stroganova, Tatiana A

2017-01-01

The brain mechanisms that integrate the separate features of sensory input into a meaningful percept depend upon the prior experience of interaction with the object and differ between categories of objects. Recent studies using representational similarity analysis (RSA) have characterized either the spatial patterns of brain activity for different categories of objects or described how category structure in neuronal representations emerges in time, but never simultaneously. Here we applied a novel, region-based, multivariate pattern classification approach in combination with RSA to magnetoencephalography data to extract activity associated with qualitatively distinct processing stages of visual perception. We asked participants to name what they see whilst viewing bitonal visual stimuli of two categories predominantly shaped by either value-dependent or sensorimotor experience, namely faces and tools, and meaningless images. We aimed to disambiguate the spatiotemporal patterns of brain activity between the meaningful categories and determine which differences in their processing were attributable to either perceptual categorization per se , or later-stage mentalizing-related processes. We have extracted three stages of cortical activity corresponding to low-level processing, category-specific feature binding, and supra-categorical processing. All face-specific spatiotemporal patterns were associated with bilateral activation of ventral occipito-temporal areas during the feature binding stage at 140-170 ms. The tool-specific activity was found both within the categorization stage and in a later period not thought to be associated with binding processes. The tool-specific binding-related activity was detected within a 210-220 ms window and was located to the intraparietal sulcus of the left hemisphere. Brain activity common for both meaningful categories started at 250 ms and included widely distributed assemblies within parietal, temporal, and prefrontal regions. Furthermore, we hypothesized and tested whether activity within face and tool-specific binding-related patterns would demonstrate oppositely acting effects following procedural perceptual learning. We found that activity in the ventral, face-specific network increased following the stimuli repetition. In contrast, tool processing in the dorsal network adapted by reducing its activity over the repetition period. Altogether, we have demonstrated that activity associated with visual processing of faces and tools during the categorization stage differ in processing timing, brain areas involved, and in their dynamics underlying stimuli learning.

"Enheduanna-A Manifesto of Falling" Live Brain-Computer Cinema Performance: Performer and Audience Participation, Cognition and Emotional Engagement Using Multi-Brain BCI Interaction.

PubMed

Zioga, Polina; Pollick, Frank; Ma, Minhua; Chapman, Paul; Stefanov, Kristian

2018-01-01

The fields of neural prosthetic technologies and Brain-Computer Interfaces (BCIs) have witnessed in the past 15 years an unprecedented development, bringing together theories and methods from different scientific fields, digital media, and the arts. More in particular, artists have been amongst the pioneers of the design of relevant applications since their emergence in the 1960s, pushing the boundaries of applications in real-life contexts. With the new research, advancements, and since 2007, the new low-cost commercial-grade wireless devices, there is a new increasing number of computer games, interactive installations, and performances that involve the use of these interfaces, combining scientific, and creative methodologies. The vast majority of these works use the brain-activity of a single participant. However, earlier, as well as recent examples, involve the simultaneous interaction of more than one participants or performers with the use of Electroencephalography (EEG)-based multi-brain BCIs. In this frame, we discuss and evaluate "Enheduanna-A Manifesto of Falling," a live brain-computer cinema performance that enables for the first time the simultaneous real-time multi-brain interaction of more than two participants, including a performer and members of the audience, using a passive EEG-based BCI system in the context of a mixed-media performance. The performance was realised as a neuroscientific study conducted in a real-life setting. The raw EEG data of seven participants, one performer and two different members of the audience for each performance, were simultaneously recorded during three live events. The results reveal that the majority of the participants were able to successfully identify whether their brain-activity was interacting with the live video projections or not. A correlation has been found between their answers to the questionnaires, the elements of the performance that they identified as most special, and the audience's indicators of attention and emotional engagement. Also, the results obtained from the performer's data analysis are consistent with the recall of working memory representations and the increase of cognitive load. Thus, these results prove the efficiency of the interaction design, as well as the importance of the directing strategy, dramaturgy and narrative structure on the audience's perception, cognitive state, and engagement.

Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases: A Phase 1 Study (ISIDE-BM-1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferro, Marica; Chiesa, Silvia; Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it

Purpose: To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with <5 brain metastases using a standard linear accelerator. Materials and Methods: The whole brain plus 3-mm margin was defined as the planning target volume (PTV{sub wb}), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTV{sub m}). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTV{sub m} was progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy),more » whereas the PTV{sub wb} was always treated with 30 Gy (3 Gy per fraction) in all patients. The dose-limiting toxicity was evaluated providing that 3 months of follow-up had occurred after the treatment of a 6-patient cohort. Results: Thirty patients were enrolled in the study (dose PTV{sub m}: 35 Gy, 8 patients; 40 Gy, 6 patients; 45 Gy, 6 patients; 50 Gy, 10 patients). The number of treated brain metastases was 1 in 18 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. Three patients experienced dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12 months and 53%, respectively. No patient showed late toxicity. Conclusions: In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.« less

“Enheduanna—A Manifesto of Falling” Live Brain-Computer Cinema Performance: Performer and Audience Participation, Cognition and Emotional Engagement Using Multi-Brain BCI Interaction

PubMed Central

Zioga, Polina; Pollick, Frank; Ma, Minhua; Chapman, Paul; Stefanov, Kristian

2018-01-01

The fields of neural prosthetic technologies and Brain-Computer Interfaces (BCIs) have witnessed in the past 15 years an unprecedented development, bringing together theories and methods from different scientific fields, digital media, and the arts. More in particular, artists have been amongst the pioneers of the design of relevant applications since their emergence in the 1960s, pushing the boundaries of applications in real-life contexts. With the new research, advancements, and since 2007, the new low-cost commercial-grade wireless devices, there is a new increasing number of computer games, interactive installations, and performances that involve the use of these interfaces, combining scientific, and creative methodologies. The vast majority of these works use the brain-activity of a single participant. However, earlier, as well as recent examples, involve the simultaneous interaction of more than one participants or performers with the use of Electroencephalography (EEG)-based multi-brain BCIs. In this frame, we discuss and evaluate “Enheduanna—A Manifesto of Falling,” a live brain-computer cinema performance that enables for the first time the simultaneous real-time multi-brain interaction of more than two participants, including a performer and members of the audience, using a passive EEG-based BCI system in the context of a mixed-media performance. The performance was realised as a neuroscientific study conducted in a real-life setting. The raw EEG data of seven participants, one performer and two different members of the audience for each performance, were simultaneously recorded during three live events. The results reveal that the majority of the participants were able to successfully identify whether their brain-activity was interacting with the live video projections or not. A correlation has been found between their answers to the questionnaires, the elements of the performance that they identified as most special, and the audience's indicators of attention and emotional engagement. Also, the results obtained from the performer's data analysis are consistent with the recall of working memory representations and the increase of cognitive load. Thus, these results prove the efficiency of the interaction design, as well as the importance of the directing strategy, dramaturgy and narrative structure on the audience's perception, cognitive state, and engagement. PMID:29666566

Distinctive time-lagged resting-state networks revealed by simultaneous EEG-fMRI.

PubMed

Feige, Bernd; Spiegelhalder, Kai; Kiemen, Andrea; Bosch, Oliver G; Tebartz van Elst, Ludger; Hennig, Jürgen; Seifritz, Erich; Riemann, Dieter

2017-01-15

Functional activation as evidenced by blood oxygen level-dependent (BOLD) functional MRI changes or event-related EEG is known to closely follow patterns of stimulation or self-paced action. Any lags are compatible with axonal conduction velocities and neural integration times. The important analysis of resting state networks is generally based on the assumption that these principles also hold for spontaneous fluctuations in brain activity. Previous observations using simultaneous EEG and fMRI indicate that slower processes, with delays in the seconds range, determine at least part of the relationship between spontaneous EEG and fMRI. To assess this relationship systematically, we used deconvolution analysis of EEG-fMRI during the resting state, assessing the relationship between EEG frequency bands and fMRI BOLD across the whole brain while allowing for time lags of up to 10.5s. Cluster analysis, identifying similar BOLD time courses in relation to EEG band power peaks, showed a clear segregation of functional subsystems of the brain. Our analysis shows that fMRI BOLD increases commonly precede EEG power increases by seconds. Most zero-lag correlations, on the other hand, were negative. This indicates two main distinct neuromodulatory mechanisms: an "idling" mechanism of simultaneous electric and metabolic network anticorrelation and a "regulatory" mechanism in which metabolic network activity precedes increased EEG power by some seconds. This has to be taken into consideration in further studies which address the causal and functional relationship of metabolic and electric brain activity patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

Different Simultaneous Sleep States in the Hippocampus and Neocortex.

PubMed

Emrick, Joshua J; Gross, Brooks A; Riley, Brett T; Poe, Gina R

2016-12-01

Investigators assign sleep-waking states using brain activity collected from a single site, with the assumption that states occur at the same time throughout the brain. We sought to determine if sleep-waking states differ between two separate structures: the hippocampus and neocortex. We measured electrical signals (electroencephalograms and electromyograms) during sleep from the hippocampus and neocortex of five freely behaving adult male rats. We assigned sleep-waking states in 10-sec epochs based on standard scoring criteria across a 4-h recording, then analyzed and compared states and signals from simultaneous epochs between sites. We found that the total amount of each state, assigned independently using the hippocampal and neocortical signals, was similar between the hippocampus and neocortex. However, states at simultaneous epochs were different as often as they were the same (P = 0.82). Furthermore, we found that the progression of states often flowed through asynchronous state-pairs led by the hippocampus. For example, the hippocampus progressed from transition-to-rapid eye movement sleep to rapid eye movement sleep before the neocortex more often than in synchrony with the neocortex (38.7 ± 16.2% versus 15.8 ± 5.6% mean ± standard error of the mean). We demonstrate that hippocampal and neocortical sleep-waking states often differ in the same epoch. Consequently, electrode location affects estimates of sleep architecture, state transition timing, and perhaps even percentage of time in sleep states. Therefore, under normal conditions, models assuming brain state homogeneity should not be applied to the sleeping or waking brain. © 2016 Associated Professional Sleep Societies, LLC.

Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

PubMed

Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

2016-09-01

Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

Brain Activations for Vestibular Stimulation and Dual Tasking Change with Spaceflight

NASA Technical Reports Server (NTRS)

Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia; De Dios, Yiri; Gadd, Nichole; Wood, Scott; Riascos, Roy; Kofman, Igor; Bloomberg, Jacob; Mulavara, Ajitkumar;

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Experimental validation of the influence of white matter anisotropy on the intracranial EEG forward solution

PubMed Central

Schomer, Donald L.; Dehghani, Nima; Ulbert, Istvan; Cash, Sydney; Papavasiliou, Steve; Eisenberg, Solomon R.; Dale, Anders M.; Halgren, Eric

2010-01-01

Forward solutions with different levels of complexity are employed for localization of current generators, which are responsible for the electric and magnetic fields measured from the human brain. The influence of brain anisotropy on the forward solution is poorly understood. The goal of this study is to validate an anisotropic model for the intracranial electric forward solution by comparing with the directly measured ‘gold standard’. Dipolar sources are created at known locations in the brain and intracranial electroencephalogram (EEG) is recorded simultaneously. Isotropic models with increasing level of complexity are generated along with anisotropic models based on Diffusion tensor imaging (DTI). A Finite Element Method based forward solution is calculated and validated using the measured data. Major findings are (1) An anisotropic model with a linear scaling between the eigenvalues of the electrical conductivity tensor and water self-diffusion tensor in brain tissue is validated. The greatest improvement was obtained when the stimulation site is close to a region of high anisotropy. The model with a global anisotropic ratio of 10:1 between the eigenvalues (parallel: tangential to the fiber direction) has the worst performance of all the anisotropic models. (2) Inclusion of cerebrospinal fluid as well as brain anisotropy in the forward model is necessary for an accurate description of the electric field inside the skull. The results indicate that an anisotropic model based on the DTI can be constructed non-invasively and shows an improved performance when compared to the isotropic models for the calculation of the intracranial EEG forward solution. Electronic supplementary material The online version of this article (doi:10.1007/s10827-009-0205-z) contains supplementary material, which is available to authorized users. PMID:20063051

Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

NASA Astrophysics Data System (ADS)

Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

2016-05-01

The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

Thermodynamic laws apply to brain function.

PubMed

Salerian, Alen J

2010-02-01

Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

Oscillatory frontal theta responses are increased upon bisensory stimulation.

PubMed

Sakowitz, O W; Schürmann, M; Başar, E

2000-05-01

To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

PubMed Central

Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

2014-01-01

Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

Coexistence of Stochastic Oscillations and Self-Organized Criticality in a Neuronal Network: Sandpile Model Application.

PubMed

Saeedi, Alireza; Jannesari, Mostafa; Gharibzadeh, Shahriar; Bakouie, Fatemeh

2018-04-01

Self-organized criticality (SOC) and stochastic oscillations (SOs) are two theoretically contradictory phenomena that are suggested to coexist in the brain. Recently it has been shown that an accumulation-release process like sandpile dynamics can generate SOC and SOs simultaneously. We considered the effect of the network structure on this coexistence and showed that the sandpile dynamics on a small-world network can produce two power law regimes along with two groups of SOs-two peaks in the power spectrum of the generated signal simultaneously. We also showed that external stimuli in the sandpile dynamics do not affect the coexistence of SOC and SOs but increase the frequency of SOs, which is consistent with our knowledge of the brain.

Simultaneous Solar Maximum Mission and Very Large Array (VLA) observations of solar active regions

NASA Technical Reports Server (NTRS)

Lang, K. R.

1985-01-01

Simultaneous observations of solar active regions with the Solar Maximum Mission (SMM) Satellite and the Very Large Array (VLA) have been obtained and analyzed. Combined results enhance the scientific return for beyond that expeted from using either SMM or VLA alone. A total of two weeks of simultaneous SMM/VLA data were obtained. The multiple wavelength VLA observations were used to determine the temperature and magnetic structure at different heights within coronal loops. These data are compared with simultaneous SMM observations. Several papers on the subject are in progress. They include VLA observations of compact, transient sources in the transition region; simultaneous SMM/VLA observations of the coronal loops in one active region and the evolution of another one; and sampling of the coronal plasma using thermal cyclotron lines (magnetic field - VLA) and soft X ray spectral lines (electron density and electron temperaure-SMM).

Age related rise in lactate and its correlation with lactate dehydrogenase (LDH) status in post-mitochondrial fractions isolated from different regions of brain in mice.

PubMed

Datta, Siddhartha; Chakrabarti, Nilkanta

2018-04-18

Rise in brain lactate is the hallmark of ageing. Separate studies report that ageing is associated with elevation of lactate level and alterations of lactate dehydrogenase (LDH)-A/B mRNA-expression-ratio in cerebral cortex and hippocampus. However, age related lactate rise in brain and its association with LDH status and their brain regional variations are still elusive. In the present study, level of lactate, LDH (A and B) activity and LDH-A expression were evaluated in post-mitochondrial fraction of tissues isolated from four different brain regions (cerebral cortex, hippocampus, substantia nigra and cerebellum) of young and aged mice. Lactate levels elevated in four brain regions with maximum rise in substantia nigra of aged mice. LDH-A protein expression and its activity decreased in cerebral cortex, hippocampus and substantia nigra without any changes of these parameters in cerebellum of aged mice. LDH-B activity decreased in hippocampus, substantia nigra and cerebellum whereas its activity remains unaltered in cerebral cortex of aged mice. Accordingly, the ratio of LDH-A/LDH-B-activity remains unaltered in hippocampus and substantia nigra, decreased in cerebral cortex and increased in cerebellum. Therefore, rise of lactate in three brain regions (cerebral cortex, hippocampus, substantia nigra) appeared to be not correlated with the alterations of its regulatory enzymes activities in these three brain regions, rather it supports the fact of involvement of other mechanisms, like lactate transport and/or aerobic/anaerobic metabolism as the possible cause(s) of lactate rise in these three brain regions. The increase in LDH-A/LDH-B-activity-ratio appeared to be positively correlated with elevated lactate level in cerebellum of aged mice. Overall, the present study indicates that the mechanism of rise in lactate in brain varies with brain regions where LDH status plays an important role during ageing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Generation of Individual Whole-Brain Atlases With Resting-State fMRI Data Using Simultaneous Graph Computation and Parcellation.

PubMed

Wang, J; Hao, Z; Wang, H

2018-01-01

The human brain can be characterized as functional networks. Therefore, it is important to subdivide the brain appropriately in order to construct reliable networks. Resting-state functional connectivity-based parcellation is a commonly used technique to fulfill this goal. Here we propose a novel individual subject-level parcellation approach based on whole-brain resting-state functional magnetic resonance imaging (fMRI) data. We first used a supervoxel method known as simple linear iterative clustering directly on resting-state fMRI time series to generate supervoxels, and then combined similar supervoxels to generate clusters using a clustering method known as graph-without-cut (GWC). The GWC approach incorporates spatial information and multiple features of the supervoxels by energy minimization, simultaneously yielding an optimal graph and brain parcellation. Meanwhile, it theoretically guarantees that the actual cluster number is exactly equal to the initialized cluster number. By comparing the results of the GWC approach and those of the random GWC approach, we demonstrated that GWC does not rely heavily on spatial structures, thus avoiding the challenges encountered in some previous whole-brain parcellation approaches. In addition, by comparing the GWC approach to two competing approaches, we showed that GWC achieved better parcellation performances in terms of different evaluation metrics. The proposed approach can be used to generate individualized brain atlases for applications related to cognition, development, aging, disease, personalized medicine, etc. The major source codes of this study have been made publicly available at https://github.com/yuzhounh/GWC.

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xu; Zhou, Jianying; Chin, Mark H

2010-02-15

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.« less

Targeted Imaging and Chemo-Phototherapy of Brain Cancer by a Multifunctional Drug Delivery System.

PubMed

Hao, Yongwei; Wang, Lei; Zhao, Yalin; Meng, Dehui; Li, Dong; Li, Haixia; Zhang, Bingxiang; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

2015-11-01

The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous quantification of nicotine, opioids, cocaine, and metabolites in human fetal postmortem brain by liquid chromatography tandem mass spectrometry

PubMed Central

Shakleya, Diaa M.

2011-01-01

A validated method for simultaneous LCMSMS quantification of nicotine, cocaine, 6-acetylmorphine (6AM), codeine, and metabolites in 100 mg fetal human brain was developed and validated. After homogenization and solid-phase extraction, analytes were resolved on a Hydro-RP analytical column with gradient elution. Empirically determined linearity was from 5–5,000 pg/mg for cocaine and benzoylecgonine (BE), 25–5,000 pg/mg for cotinine, ecgonine methyl ester (EME) and 6AM, 50–5000 pg/mg for trans-3-hydroxycotinine (OH-cotinine) and codeine, and 250–5,000 pg/mg for nicotine. Potential endogenous and exogenous interferences were resolved. Intra- and inter-assay analytical recoveries were ≥92%, intra- and inter-day and total assay imprecision were ≤14% RSD and extraction efficiencies were ≥67.2% with ≤83% matrix effect. Method applicability was demonstrated with a postmortem fetal brain containing 40 pg/mg cotinine, 65 pg/mg OH-cotinine, 13 pg/mg cocaine, 34 pg/mg EME, and 525 pg/mg BE. This validated method is useful for determination of nicotine, opioid, and cocaine biomarkers in brain. PMID:19229524

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

PubMed

Fink, Ericka L; Panigrahy, A; Clark, R S B; Fitz, C R; Landsittel, D; Kochanek, P M; Zuccoli, G

2013-08-01

To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Long-term variability of importance of brain regions in evolving epileptic brain networks

NASA Astrophysics Data System (ADS)

Geier, Christian; Lehnertz, Klaus

2017-04-01

We investigate the temporal and spatial variability of the importance of brain regions in evolving epileptic brain networks. We construct these networks from multiday, multichannel electroencephalographic data recorded from 17 epilepsy patients and use centrality indices to assess the importance of brain regions. Time-resolved indications of highest importance fluctuate over time to a greater or lesser extent, however, with some periodic temporal structure that can mostly be attributed to phenomena unrelated to the disease. In contrast, relevant aspects of the epileptic process contribute only marginally. Indications of highest importance also exhibit pronounced alternations between various brain regions that are of relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches. Nonetheless, these findings may guide new developments for individualized diagnosis, treatment, and control.

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

PubMed

Gejl, Michael; Gjedde, Albert; Brock, Birgitte; Møller, Arne; van Duinkerken, Eelco; Haahr, Hanne L; Hansen, Charlotte T; Chu, Pei-Ling; Stender-Petersen, Kirstine L; Rungby, Jørgen

2018-03-01

The aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus. In this patient-blinded, crossover study, 26 participants with type 1 diabetes mellitus attended two randomised experimental visits: one hypoglycaemic clamp (PG 2.8 ± 0.2 mmol/l, approximate duration 55 min) and one euglycaemic clamp (PG 5.5 mmol/l ± 10%). PG levels were maintained by hyperinsulinaemic glucose clamping. Cognitive functioning was assessed during hypoglycaemia and euglycaemia conditions using a modified version of the digit symbol substitution test (mDSST) and control DSST (cDSST). Simultaneously, regional cerebral blood flow (rCBF) was measured in pre-specified brain regions by six H 2 15 O-positron emission tomographies (PET) per session. Working memory was impaired during hypoglycaemia as indicated by a statistically significantly lower mDSST score (estimated treatment difference [ETD] -0.63 [95% CI -1.13, -0.14], p = 0.014) and a statistically significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p = 0.013) compared with euglycaemia. During hypoglycaemia, mDSST task performance was associated with increased activity in the frontal lobe regions, superior parietal lobe and thalamus, and decreased activity in the temporal lobe regions (p < 0.05). Working memory activation (mDSST - cDSST) statistically significantly increased blood flow in the striatum during hypoglycaemia (ETD 0.0374% [95% CI 0.0157, 0.0590], p = 0.002). During hypoglycaemia (mean PG 2.9 mmol/l), working memory performance was impaired. Altered performance was associated with significantly increased blood flow in the striatum, a part of the basal ganglia implicated in regulating motor functions, memory, language and emotion. NCT01789593, clinicaltrials.gov FUNDING: This study was funded by Novo Nordisk.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

Determination of regional brain temperature using proton magnetic resonance spectroscopy to assess brain-body temperature differences in healthy human subjects.

PubMed

Childs, Charmaine; Hiltunen, Yrjö; Vidyasagar, Rishma; Kauppinen, Risto A

2007-01-01

Proton magnetic resonance spectroscopy ((1)H MRS) was used to determine brain temperature in healthy volunteers. Partially water-suppressed (1)H MRS data sets were acquired at 3T from four different gray matter (GM)/white matter (WM) volumes. Brain temperatures were determined from the chemical-shift difference between the CH(3) of N-acetyl aspartate (NAA) at 2.01 ppm and water. Brain temperatures in (1)H MRS voxels of 2 x 2 x 2 cm(3) showed no substantial heterogeneity. The volume-averaged temperature from single-voxel spectroscopy was compared with body temperatures obtained from the oral cavity, tympanum, and temporal artery regions. The mean brain parenchyma temperature was 0.5 degrees C cooler than readings obtained from three extra-brain sites (P < 0.01). (1)H MRS imaging (MRSI) data were acquired from a slice encompassing the single-voxel volumes to assess the ability of spectroscopic imaging to determine regional brain temperature within the imaging slice. Brain temperature away from the center of the brain determined by MRSI differed from that obtained by single-voxel MRS in the same brain region, possibly due to a poor line width (LW) in MRSI. The data are discussed in the light of proposed brain-body temperature gradients and the use of (1)H MRSI to monitor brain temperature in pathologies, such as brain trauma.

Intranasal Administration of PACAP: Uptake by Brain and Brain Region Targeting with Cyclodextrins

PubMed Central

Nonaka, Naoko; Farr, Susan A.; Nakamachi, Tomoya; Morley, John E.; Nakamura, Masanori; Shioda, Seiji; Banks, William A.

2012-01-01

Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent neurotrophic and neuroprotectant that is transported across the blood-brain barrier in amounts sufficient to affect brain function. However, its short half-life in blood makes it difficult to administer peripherally. Here, we determined whether the radioactively labeled 38 amino acid form of PACAP can enter the brain after intranasal (i.n.) administration. Occipital cortex and striatum were the regions with the highest uptake, peaking at levels of about 2-4 percent of the injected dose per g of brain region. Inclusion of unlabeled PACAP greatly increased retention of I-PACAP by brain probably because of inhibition of the brain-to-blood efflux transporter for PACAP located at the blood-brain barrier. Sufficient amounts of PACAP could be delivered to the brain to affect function as shown by improvement of memory in aged SAMP8 mice, a model of Alzheimer’s disease. We found that each of three cyclodextrins when included in the i.n. injection produced a unique distribution pattern of I-PACAP among brain regions. As examples, β-cyclodextrin greatly increased uptake by the occipital cortex and hypothalamus, α-cyclodextrin increased uptake by the olfactory bulb and decreased uptake by the occipital cortex and striatum, and (2-hydropropyl)-β-cyclodextrin increased uptake by the thalamus and decreased uptake by the striatum. These results show that therapeutic amounts of PACAP can be delivered to the brain by intranasal administration and that cyclodextrins may be useful in the therapeutic targeting of peptides to specific brain regions. PMID:22687366

Fused cerebral organoids model interactions between brain regions.

PubMed

Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Control-related systems in the human brain

PubMed Central

Power, Jonathan D; Petersen, Steven E

2013-01-01

A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. PMID:23347645

Functional Characterization of 5-HT1B Receptor Drugs in Nonhuman Primates Using Simultaneous PET-MR.

PubMed

Hansen, Hanne D; Mandeville, Joseph B; Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Knudsen, Gitte M

2017-11-01

In the present study, we used a simultaneous PET-MR experimental design to investigate the effects of functionally different compounds (agonist, partial agonist, and antagonist) on 5-HT 1B receptor (5-HT 1B R) occupancy and the associated hemodynamic responses. In anesthetized male nonhuman primates ( n = 3), we used positron emission tomography (PET) imaging with the radioligand [ 11 C]AZ10419369 administered as a bolus followed by constant infusion to measure changes in 5-HT 1B R occupancy. Simultaneously, we measured changes in cerebral blood volume (CBV) as a proxy of drug effects on neuronal activity. The 5-HT 1B R partial agonist AZ10419369 elicited a dose-dependent biphasic hemodynamic response that was related to the 5-HT 1B R occupancy. The magnitude of the response was spatially overlapping with high cerebral 5-HT 1B R densities. High doses of AZ10419369 exerted an extracranial tissue vasoconstriction that was comparable to the less blood-brain barrier-permeable 5-HT 1B R agonist sumatriptan. By contrast, injection of the antagonist GR127935 did not elicit significant hemodynamic responses, even at a 5-HT 1B R cerebral occupancy similar to the one obtained with a high dose of AZ10419369. Given the knowledge we have of the 5-HT 1B R and its function and distribution in the brain, the hemodynamic response informs us about the functionality of the given drug: changes in CBV are only produced when the receptor is stimulated by the partial agonist AZ10419369 and not by the antagonist GR127935, consistent with low basal occupancy by endogenous serotonin. SIGNIFICANCE STATEMENT We here show that combined simultaneous positron emission tomography and magnetic resonance imaging uniquely enables the assessment of CNS active compounds. We conducted a series of pharmacological interventions to interrogate 5-HT 1B receptor binding and function and determined blood-brain barrier passage of drugs and demonstrate target involvement. Importantly, we show how the spatial and temporal effects on brain hemodynamics provide information about pharmacologically driven downstream CNS drug effects; the brain hemodynamic response shows characteristic dose-related effects that differ depending on agonistic or antagonistic drug characteristics and on local 5-HT 1B receptor density. The technique lends itself to a comprehensive in vivo investigation and understanding of drugs' effects in the brain. Copyright © 2017 the authors 0270-6474/17/3710671-08$15.00/0.

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.

PubMed

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-08-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a "smart needle" to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure.

Local cortical dynamics of burst suppression in the anaesthetized brain.

PubMed

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.

Describing functional diversity of brain regions and brain networks

PubMed Central

Anderson, Michael L.; Kinnison, Josh; Pessoa, Luiz

2013-01-01

Despite the general acceptance that functional specialization plays an important role in brain function, there is little consensus about its extent in the brain. We sought to advance the understanding of this question by employing a data-driven approach that capitalizes on the existence of large databases of neuroimaging data. We quantified the diversity of activation in brain regions as a way to characterize the degree of functional specialization. To do so, brain activations were classified in terms of task domains, such as vision, attention, and language, which determined a region’s functional fingerprint. We found that the degree of diversity varied considerably across the brain. We also quantified novel properties of regions and of networks that inform our understanding of several task-positive and task-negative networks described in the literature, including defining functional fingerprints for entire networks and measuring their functional assortativity, namely the degree to which they are composed of regions with similar functional fingerprints. Our results demonstrate that some brain networks exhibit strong assortativity, whereas other networks consist of relatively heterogeneous parts. In sum, rather than characterizing the contributions of individual brain regions using task-based functional attributions, we instead quantified their dispositional tendencies, and related those to each region’s affiliative properties in both task-positive and task-negative contexts. PMID:23396162

Transcriptional regulation of brain gene expression in response to a territorial intrusion

PubMed Central

Sanogo, Yibayiri O.; Band, Mark; Blatti, Charles; Sinha, Saurabh; Bell, Alison M.

2012-01-01

Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem. Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges. PMID:23097509

"Missing links" in borderline personality disorder: loss of neural synchrony relates to lack of emotion regulation and impulse control.

PubMed

Williams, Leanne M; Sidis, Anna; Gordon, Evian; Meares, Russell A

2006-05-01

Symptoms of borderline personality disorder (BPD) may reflect distinct breakdowns in the integration of posterior and frontal brain networks. We used a high temporal resolution measure (40-Hz gamma phase synchrony) of brain activity to examine the connectivity of brain function in BPD. Unmedicated patients with BPD (n = 15) and age-and sex-matched healthy control subjects (n = 15) undertook a task requiring discrimination of salient from background tones. In response to salient stimuli, the magnitude and latency of peak gamma phase synchrony for early (0-150 ms post stimulus) and late (250-500 ms post stimulus) phases were calculated for frontal and posterior regions and for left and right hemispheres. We recorded skin conductance responses (SCRs) and reaction time (RT) simultaneously to examine the contribution of arousal and performance. Compared with controls, patients with BPD had a significant delay in early posterior gamma synchrony and a reduction in right hemisphere late gamma synchrony in response to salient stimuli. Both SCR onset and RT were also delayed in BPD, but independently from differences in synchrony. The delay in posterior synchrony was associated with cognitive symptoms, and reduced right hemisphere synchrony was associated with impulsivity. These findings suggest that distinct impairments in the functional connectivity of neural systems for orienting to salient input underlie core dimensions of cognitive disturbance and poor impulse control in BPD.