scholarly journals Characterizing pupil dynamics coupling to brain state fluctuation based on lateral hypothalamic activity

2021 ◽  
Author(s):  
Kengo Takahashi ◽  
Filip Sobczak ◽  
Patricia Pais-Roldán ◽  
Xin Yu
Keyword(s):  
Brain Activity ◽  
Field Potential ◽  
Neuronal Cell ◽  
Cell Types ◽  
State Regulation ◽  
Anterior Cingulate ◽  
Brain State ◽  
Dependent Manner ◽  
Whole Brain ◽  
Brain Fmri

AbstractPupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain state changes can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and the whole brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional MRI (fMRI) data showed opposite correlation features to pupil dynamics, demonstrating an LH activity-dependent manner. Our results demonstrate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, indicating a role of the latter in brain state regulation.

Clinical relevance of the neurotrophins and their receptors

2006 ◽  
Vol 110 (2) ◽  
pp. 175-191 ◽  
Author(s):  
Shelley J. Allen ◽  
David Dawbarn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Disease Process ◽  
Neuronal Cell ◽  
Cell Types ◽  
Dependent Manner ◽  
Disease States ◽  
Neuronal Tissues

The neurotrophins are growth factors required by discrete neuronal cell types for survival and maintenance, with a broad range of activities in the central and peripheral nervous system in the developing and adult mammal. This review examines their role in diverse disease states, including Alzheimer's disease, depression, pain and asthma. In addition, the role of BDNF (brain-derived neurotrophic factor) in synaptic plasticity and memory formation is discussed. Unlike the other neurotrophins, BDNF is secreted in an activity-dependent manner that allows the highly controlled release required for synaptic regulation. Evidence is discussed which shows that sequestration of NGF (nerve growth factor) is able to reverse symptoms of inflammatory pain and asthma in animal models. Both pain and asthma show an underlying pathophysiology linked to increases in endogenous NGF and subsequent NGF-dependent increase in BDNF. Conversely, in Alzheimer's disease, there is a role for NGF in the treatment of the disease and a recent clinical trial has shown benefit from its exogenous application. In addition, reductions in BDNF, and changes in the processing and usage of NGF, are evident and it is possible that both NGF and BDNF play a part in the aetiology of the disease process. This highly selective choice of functions and disease states related to neurotrophin function, although in no way comprehensive, illustrates the importance of the neurotrophins in the brain, the peripheral nervous system and in non-neuronal tissues. Ways in which the neurotrophins, their receptors or agonists/antagonists may act therapeutically are discussed.

scholarly journals Mass univariate testing biases the detection of interaction effects in whole-brain analysis of variance

2017 ◽  
Author(s):  
Robert S. Chavez ◽  
Dylan D. Wagner
Keyword(s):  
Analysis Of Variance ◽  
Signal To Noise Ratio ◽  
Brain Activity ◽  
Interaction Effects ◽  
Sample Sizes ◽  
Whole Brain ◽  
Two Factors ◽  
Independent Variable ◽  
Simulated Analysis ◽  
Brain Fmri

AbstractWhole-brain analysis of variance (ANOVA) is a common analytic approach in cognitive neuroscience. Researchers are often interested in exploring whether brain activity reflects to the interaction of two factors. Disordinal interactions — where there is a reversal of the effect of one independent variable at a level of a second independent variable — are common in the literature. It is well established in power-analyses of factorial ANOVAs that certain patterns of interactions, such as disordinal (e.g., cross-over interactions) require less power than others to detect. This fact, combined with the perils of mass univariate testing suggests that testing for interactions in whole-brain ANOVAs, may be biased towards the detection of disordinal interactions. Here, we report on a series of simulated analysis --including whole-brain fMRI data using realistic multi-source noise parameters-- that demonstrate a bias towards the detection of disordinal interactions in mass-univariate contexts. Moreover, results of these simulations indicated that spurious disordinal interactions are found at common thresholds and cluster sizes at the group level. Moreover, simulations based on implanting true ordinal interaction effects can nevertheless appear like crossover effects at realistic levels of signal-to-noise ratio (SNR) when performing mass univariate testing at the whole-brain level, potentially leading to erroneous conclusions when interpreted as is. Simulations of varying sample sizes and SNR levels show that this bias is driven primarily by SNR and larger sample sizes do little to ameliorate this issue. Together, the results of these simulations argue for caution when searching for ordinal interactions in whole-brain ANOVA.

scholarly journals Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness

2021 ◽  
Vol 17 (7) ◽  
pp. e1009139
Author(s):  
Yonatan Sanz Perl ◽  
Carla Pallavicini ◽  
Ignacio Pérez Ipiña ◽  
Athena Demertzi ◽  
Vincent Bonhomme ◽  
...  
Keyword(s):  
Computational Models ◽  
Brain Activity ◽  
Relevant Information ◽  
Complete Characterization ◽  
Brain State ◽  
Whole Brain ◽  
Brain Injured ◽  
Level Of Consciousness ◽  
The Stability ◽  
Injured Patients

Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.

S -Ketamine Anesthesia Increases Cerebral Blood Flow in Excess of the Metabolic Needs in Humans

2005 ◽  
Vol 103 (2) ◽  
pp. 258-268 ◽  
Author(s):  
Jaakko W. Långsjö ◽  
Anu Maksimow ◽  
Elina Salmi ◽  
Kaike Kaisti ◽  
Sargo Aalto ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Brain Structures ◽  
Anterior Cingulate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Whole Brain

Background Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans. Methods Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia. Whole brain estimates for cerebral blood volume were obtained using kinetic modeling. Results The mean +/- SD serum S-ketamine concentration was 159 +/- 21 ng/ml at the subanesthetic and 1,959 +/- 442 ng/ml at the anesthetic levels. The total S-ketamine dose was 10.4 mg/kg. S-ketamine increased heart rate (maximally by 43.5%) and mean blood pressure (maximally by 27.0%) in a concentration-dependent manner (P = 0.001 for both). Subanesthetic S-ketamine increased whole brain CBF by 13.7% (P = 0.035). The greatest regional CBF increase was detected in the anterior cingulate (31.6%; P = 0.010). No changes were detected in CMRO2. Anesthetic S-ketamine increased whole brain CBF by 36.4% (P = 0.006) but had no effect on whole brain CMRO2 or GMR. Regionally, CBF was increased in nearly all brain structures studied (greatest increase in the insula 86.5%; P < 0.001), whereas CMRO2 increased only in the frontal cortex (by 15.7%; P = 0.007) and GMR increased only in the thalamus (by 11.7%; P = 0.010). Cerebral blood volume was increased by 51.9% (P = 0.011) during anesthesia. Conclusions S-ketamine-induced CBF increases exceeded the minor changes in CMRO2 and GMR during anesthesia.

scholarly journals Population receptive fields in non-human primates from whole-brain fMRI and large-scale neurophysiology in visual cortex in visual cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Peter Christiaan Klink ◽  
Xing Chen ◽  
Vim Vanduffel ◽  
Pieter Roelfsema
Keyword(s):  
Visual Cortex ◽  
Receptive Field ◽  
Large Scale ◽  
Receptive Fields ◽  
Field Potential ◽  
Whole Brain ◽  
Network Nodes ◽  
Gamma Power ◽  
Retinotopic Organization ◽  
Brain Fmri

Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF-maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake non-human primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF-models based on the fMRI BOLD-signal, multi-unit spiking activity (MUA) and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. FMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF-size with increasing eccentricity, as well as a retinotopically specific deactivation of default-mode network nodes similar to previous observations in humans.

scholarly journals Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness

2020 ◽  
Author(s):  
Yonatan Sanz Perl ◽  
Carla Pallavicini ◽  
Ignacio Pérez Ipiña ◽  
Athena Demertzi ◽  
Vincent Bonhomme ◽  
...  
Keyword(s):  
Computational Models ◽  
Brain Activity ◽  
Relevant Information ◽  
Complete Characterization ◽  
Brain State ◽  
Whole Brain ◽  
Brain Injured ◽  
Level Of Consciousness ◽  
The Stability ◽  
Injured Patients

AbstractConsciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.

scholarly journals Impaired subjective well-being in schizophrenia is associated with reduced anterior cingulate activity during reward processing

2014 ◽  
Vol 45 (3) ◽  
pp. 589-600 ◽  
Author(s):  
J. Gilleen ◽  
S. S. Shergill ◽  
S. Kapur
Keyword(s):  
Brain Activity ◽  
Well Being ◽  
Reward Processing ◽  
Anterior Cingulate ◽  
Subjective Well Being ◽  
Dorsal Anterior Cingulate Cortex ◽  
Whole Brain ◽  
Reward Anticipation ◽  
Reward Network ◽  
Healthy Participants

BackgroundPatients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network.MethodTwenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW.ResultsReward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants.ConclusionsIn patients with schizophrenia, reduced activation of the dACC during multiple aspects of reward processing is associated with lower SW. As the dACC has been widely linked to coupling of reward and action, and the link to SW is apparent over anticipation and outcome, these findings suggest that SW deficits in schizophrenia may be attributable to reduced integration of environmental rewarding cues, motivated behaviour and reward outcome.

scholarly journals Monocarboxylate Transporter 8 in Neuronal Cell Growth

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1961-1969 ◽  
Author(s):  
S. R. James ◽  
J. A. Franklyn ◽  
B. J. Reaves ◽  
V. E. Smith ◽  
S. Y. Chan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Cell Growth ◽  
Neural Development ◽  
Neuronal Cell ◽  
Normal Growth ◽  
Cell Types ◽  
Monocarboxylate Transporter ◽  
Dependent Manner ◽  
Nt2 Cells

Thyroid hormones are essential for the normal growth and development of the fetus, and even small alterations in maternal thyroid hormone status during early pregnancy may be associated with neurodevelopmental abnormalities in childhood. Mutations in the novel and specific thyroid hormone transporter monocarboxylate transporter 8 (MCT8) have been associated with severe neurodevelopmental impairment. However, the mechanism by which MCT8 influences neural development remains poorly defined. We have therefore investigated the effect of wild-type (WT) MCT8, and the previously reported L471P mutant, on the growth and function of human neuronal precursor NT2 cells as well as MCT8-null JEG-3 cells. HA-tagged WT MCT8 correctly localized to the plasma membrane in NT2 cells and increased T3 uptake in both cell types. In contrast, L471P MCT8 was largely retained in the endoplasmic reticulum and displayed no T3 transport activity. Transient overexpression of WT and mutant MCT8 proteins failed to induce endoplasmic reticular stress or apoptosis. However, MCT8 overexpression significantly repressed cell proliferation in each cell type in both the presence and absence of the active thyroid hormone T3 and in a dose-dependent manner. In contrast, L471P MCT8 showed no such influence. Finally, small interfering RNA depletion of endogenous MCT8 resulted in increased cell survival and decreased T3 uptake. Given that T3 stimulated proliferation in embryonic neuronal NT2 cells, whereas MCT8 repressed cell growth, these data suggest an entirely novel role for MCT8 in addition to T3 transport, mediated through the modulation of cell proliferation in the developing brain.

scholarly journals Origin of slow spontaneous resting-state neuronal fluctuations in brain networks

2018 ◽  
Vol 115 (26) ◽  
pp. 6858-6863 ◽  
Author(s):  
Giri P. Krishnan ◽  
Oscar C. González ◽  
Maxim Bazhenov
Keyword(s):  
Computational Model ◽  
Local Field ◽  
Resting State ◽  
Large Scale ◽  
Brain Activity ◽  
Field Potential ◽  
Ion Concentration ◽  
Brain State ◽  
The Brain

Resting- or baseline-state low-frequency (0.01–0.2 Hz) brain activity is observed in fMRI, EEG, and local field potential recordings. These fluctuations were found to be correlated across brain regions and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow resting-state fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (<0.05 Hz) activity could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra- and extracellular K+and Na+and intracellular Cl−ions, Na+/K+exchange pump, and KCC2 cotransporter. In the network model simulating resting awake-like brain state, we observed infra-slow fluctuations in the extracellular K+concentration, Na+/K+pump activation, firing rate of neurons, and local field potentials. Holding K+concentration constant prevented generation of the infra-slow fluctuations. The amplitude and peak frequency of this activity were modulated by the Na+/K+pump, AMPA/GABA synaptic currents, and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state activity observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are reported as the resting-state fluctuations in fMRI and EEG recordings.

scholarly journals Satiety, Thermosensation and Mechanosensation Regulate a Spontaneous C. elegans Sleep State

2019 ◽  
Author(s):  
Daniel L. Gonzales ◽  
Jasmine Zhou ◽  
Jacob T. Robinson
Keyword(s):  
Neural Activity ◽  
Neural Circuits ◽  
Brain Activity ◽  
External Environment ◽  
State Transitions ◽  
Brain State ◽  
Behavioral State ◽  
Chemical Signaling ◽  
Whole Brain ◽  
C Elegans

AbstractOne remarkable feature of the nervous system is its ability to rapidly and spontaneously switch between activity states. In the extreme example of sleep, animals arrest locomotion, reduce their sensitivity to sensory stimuli, and dramatically alter their neural activity. Small organisms are useful models to better understand these sudden changes in neural states because we can simultaneously observe whole-brain activity, monitor behavior and precisely regulate the external environment. Here, we show a spontaneous sleep-like behavior in C. elegans that is associated with a distinct global-brain state and regulated by both the animal’s internal physiological state and input from multiple sensory circuits. Specifically, we found that when confined in microfluidic chambers, adult worms spontaneously transition between periods of normal activity and short quiescent bouts, with behavioral state transitions occurring every few minutes. This quiescent state, which we call μSleep, meets the behavioral requirements of C. elegans sleep, is dependent on known sleep-promoting neurons ALA and RIS, and is associated with a global down-regulation of neural activity. Consistent with prior studies of C. elegans sleep, we found that μSleep is regulated by satiety and temperature. In addition, we show for the first time that quiescence can be either driven or suppressed by thermosensory input, and that animal restraint induces quiescence through mechanosensory pathways. Together, these results establish a rich model system for studying how neural and behavioral state transitions are influenced by multiple physiological and environmental conditions.Significance StatementUnique brain states govern animal behaviors like sleep and wakefulness; however, how the brain regulates these dramatic state transitions is not well understood. Brain activity can be influenced by a complex interaction between sensory circuits that monitor the external environment, neural circuits that control behavior, and internal chemical signaling. Here, we describe a platform to study behavioral states in a context that allows us to record whole-brain activity while controlling the environment and monitoring animal behavior. Specifically, we identify a pattern of sleep bouts in the roundworm C. elegans that occur when they are confined to microscopic fluidic chambers. This behavior platform provides a powerful system to study how neural circuits interact with chemical signaling to drive brain state transitions.

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