Optogenetic fMRI interrogation of brain-wide central vestibular pathways

Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject’s ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.

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Bottom-up sensory processing can decrease activity and functional connectivity in the default mode like network in rats

10.1101/482638 ◽

2018 ◽

Author(s):

Rukun Hinz ◽

Lore M. B. Peeters ◽

Disha Shah ◽

Stephan Missault ◽

Michaël Belloy ◽

...

Keyword(s):

Functional Connectivity ◽

Sensory Processing ◽

Large Scale ◽

Visual Stimulation ◽

Block Design ◽

Brain State ◽

Top Down ◽

Similar Reduction ◽

Bottom Up ◽

Default Mode

AbstractThe default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if unpredicted salient stimuli, able to trigger bottom-up attentional processes, could also result in similar reduction of activity and functional connectivity in the DMN. In this study, we investigated whether bottom-up sensory processing could influence the default mode like network (DMLN) in rats. DMLN activity was examined using block-design visual functional magnetic resonance imaging (fMRI) while its synchronization was investigated by comparing functional connectivity during a resting versus a continuously stimulated brain state by unpredicted light flashes. We demonstrated that activity in DMLN regions was decreased during visual stimulus blocks and increased during blanks. Furthermore, decreased inter-network functional connectivity between the DMLN and visual networks as well as decreased intra-network functional connectivity within the DMLN was observed during the continuous visual stimulation. These results suggest that triggering of bottom-up attention mechanisms in anesthetized rats can lead to a cascade similar to top-down orienting of attention in humans and is able to deactivate and desynchronize the DMLN.

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Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201583 ◽

2021 ◽

pp. 1-11

Author(s):

Adam S. Bernstein ◽

Steven Z. Rapcsak ◽

Michael Hornberger ◽

Manojkumar Saranathan ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Large Scale ◽

Structural Changes ◽

Thalamic Nuclei ◽

Medial Temporal Lobes ◽

Cognitive Changes ◽

Temporal Lobes ◽

Medial Geniculate ◽

Healthy Control

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

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Static and dynamic functional connectivity supports the configuration of brain networks associated with creative cognition

Scientific Reports ◽

10.1038/s41598-020-80293-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Abhishek Uday Patil ◽

Sejal Ghate ◽

Deepa Madathil ◽

Ovid J. L. Tzeng ◽

Hsu-Wen Huang ◽

...

Keyword(s):

Cognitive Processes ◽

Large Scale ◽

Brain Networks ◽

Blood Oxygen Level Dependent ◽

Detection Algorithm ◽

Brain Regions ◽

Creative Cognition ◽

Network Flexibility ◽

Community Detection Algorithm ◽

Window Approach

AbstractCreative cognition is recognized to involve the integration of multiple spontaneous cognitive processes and is manifested as complex networks within and between the distributed brain regions. We propose that the processing of creative cognition involves the static and dynamic re-configuration of brain networks associated with complex cognitive processes. We applied the sliding-window approach followed by a community detection algorithm and novel measures of network flexibility on the blood-oxygen level dependent (BOLD) signal of 8 major functional brain networks to reveal static and dynamic alterations in the network reconfiguration during creative cognition using functional magnetic resonance imaging (fMRI). Our results demonstrate the temporal connectivity of the dynamic large-scale creative networks between default mode network (DMN), salience network, and cerebellar network during creative cognition, and advance our understanding of the network neuroscience of creative cognition.

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Representational drift in the mouse visual cortex

10.1101/2020.10.05.327049 ◽

2020 ◽

Cited By ~ 1

Author(s):

Daniel Deitch ◽

Alon Rubin ◽

Yaniv Ziv

Keyword(s):

Large Scale ◽

Activity Patterns ◽

Population Level ◽

Population Activity ◽

Cortical Areas ◽

Electrophysiological Recordings ◽

The Face ◽

Visual Cortical ◽

Mouse Visual Cortex ◽

Over Time

AbstractNeuronal representations in the hippocampus and related structures gradually change over time despite no changes in the environment or behavior. The extent to which such ‘representational drift’ occurs in sensory cortical areas and whether the hierarchy of information flow across areas affects neural-code stability have remained elusive. Here, we address these questions by analyzing large-scale optical and electrophysiological recordings from six visual cortical areas in behaving mice that were repeatedly presented with the same natural movies. We found representational drift over timescales spanning minutes to days across multiple visual areas. The drift was driven mostly by changes in individual cells’ activity rates, while their tuning changed to a lesser extent. Despite these changes, the structure of relationships between the population activity patterns remained stable and stereotypic, allowing robust maintenance of information over time. Such population-level organization may underlie stable visual perception in the face of continuous changes in neuronal responses.

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Simultaneous Measurement of the BOLD Effect and Metabolic Changes in Response to Visual Stimulation Using the MEGA-PRESS Sequence at 3 T

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.644079 ◽

2021 ◽

Vol 15 ◽

Author(s):

Gerard Eric Dwyer ◽

Alexander R. Craven ◽

Justyna Bereśniewicz ◽

Katarzyna Kazimierczak ◽

Lars Ersland ◽

...

Keyword(s):

Magnetic Resonance ◽

Visual Stimulation ◽

Occipital Cortex ◽

Blood Oxygen Level Dependent ◽

Metabolic Changes ◽

Water Suppression ◽

Resonance Spectroscopy ◽

Indirect Measure ◽

Bold Effect ◽

Water Signal

The blood oxygen level dependent (BOLD) effect that provides the contrast in functional magnetic resonance imaging (fMRI) has been demonstrated to affect the linewidth of spectral peaks as measured with magnetic resonance spectroscopy (MRS) and through this, may be used as an indirect measure of cerebral blood flow related to neural activity. By acquiring MR-spectra interleaved with frames without water suppression, it may be possible to image the BOLD effect and associated metabolic changes simultaneously through changes in the linewidth of the unsuppressed water peak. The purpose of this study was to implement this approach with the MEGA-PRESS sequence, widely considered to be the standard sequence for quantitative measurement of GABA at field strengths of 3 T and lower, to observe how changes in both glutamate (measured as Glx) and GABA levels may relate to changes due to the BOLD effect. MR-spectra and fMRI were acquired from the occipital cortex (OCC) of 20 healthy participants whilst undergoing intrascanner visual stimulation in the form of a red and black radial checkerboard, alternating at 8 Hz, in 90 s blocks comprising 30 s of visual stimulation followed by 60 s of rest. Results show very strong agreement between the changes in the linewidth of the unsuppressed water signal and the canonical haemodynamic response function as well as a strong, negative, but not statistically significant, correlation with the Glx signal as measured from the OFF spectra in MEGA-PRESS pairs. Findings from this experiment suggest that the unsuppressed water signal provides a reliable measure of the BOLD effect and that correlations with associated changes in GABA and Glx levels may also be measured. However, discrepancies between metabolite levels as measured from the difference and OFF spectra raise questions regarding the reliability of the respective methods.

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Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

10.1101/866251 ◽

2019 ◽

Cited By ~ 1

Author(s):

Paloma P Maldonado ◽

Alvaro Nuno-Perez ◽

Jan Kirchner ◽

Elizabeth Hammock ◽

Julijana Gjorgjieva ◽

...

Keyword(s):

Visual Cortex ◽

Spontaneous Activity ◽

Sensory Processing ◽

Activity Patterns ◽

Network Activity ◽

Synaptic Connections ◽

Pairwise Correlations ◽

Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

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Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab251 ◽

2021 ◽

Author(s):

Giorgos Bamias ◽

Theresa T Pizarro ◽

Fabio Cominelli

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Large Scale ◽

Intestinal Inflammation ◽

Temporal Association ◽

Stricture Formation ◽

Intestinal Fibrosis ◽

Matrix Deposition ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.

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Near Real-Time Automated Early Mapping of the Perimeter of Large Forest Fires from the Aggregation of VIIRS and MODIS Active Fires in Mexico

Remote Sensing ◽

10.3390/rs12122061 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2061 ◽

Cited By ~ 1

Author(s):

Carlos Ivan Briones-Herrera ◽

Daniel José Vega-Nieva ◽

Norma Angélica Monjarás-Vega ◽

Jaime Briseño-Reyes ◽

Pablito Marcelo López-Serrano ◽

...

Keyword(s):

Real Time ◽

Forest Fires ◽

Large Scale ◽

Infrared Imaging ◽

Activity Patterns ◽

Burned Area ◽

Management Decision ◽

Coarse Scale ◽

Early Evaluation ◽

Active Fire

In contrast with current operational products of burned area, which are generally available one month after the fire, active fires are readily available, with potential application for early evaluation of approximate fire perimeters to support fire management decision making in near real time. While previous coarse-scale studies have focused on relating the number of active fires to a burned area, some local-scale studies have proposed the spatial aggregation of active fires to directly obtain early estimate perimeters from active fires. Nevertheless, further analysis of this latter technique, including the definition of aggregation distance and large-scale testing, is still required. There is a need for studies that evaluate the potential of active fire aggregation for rapid initial fire perimeter delineation, particularly taking advantage of the improved spatial resolution of the Visible Infrared Imaging Radiometer (VIIRS) 375 m, over large areas and long periods of study. The current study tested the use of convex hull algorithms for deriving coarse-scale perimeters from Moderate Resolution Imaging Spectroradiometer (MODIS) and Visible Infrared Imaging Radiometer Suite (VIIRS) active fire detections, compared against the mapped perimeter of the MODIS collection 6 (MCD64A1) burned area. We analyzed the effect of aggregation distance (750, 1000, 1125 and 1500 m) on the relationships of active fire perimeters with MCD64A1, for both individual fire perimeter prediction and total burned area estimation, for the period 2012–2108 in Mexico. The aggregation of active fire detections from MODIS and VIIRS demonstrated a potential to offer coarse-scale early estimates of the perimeters of large fires, which can be available to support fire monitoring and management in near real time. Total burned area predicted from aggregated active fires followed the same temporal behavior as the standard MCD64A1 burned area, with potential to also account for the role of smaller fires detected by the thermal anomalies. The proposed methodology, based on easily available algorithms of point aggregation, is susceptible to be utilized both for near real-time and historical fire perimeter evaluation elsewhere. Future studies might test active fires aggregation between regions or biomes with contrasting fuel characteristics and human activity patterns against medium resolution (e.g., Landsat and Sentinel) fire perimeters. Furthermore, coarse-scale active fire perimeters might be utilized to locate areas where such higher-resolution imagery can be downloaded to improve the evaluation of fire extent and impact.

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Asymmetric Integration Recorded From Vestibular-Only Cells in Response to Position Transients

Journal of Neurophysiology ◽

10.1152/jn.2002.88.4.2104 ◽

2002 ◽

Vol 88 (4) ◽

pp. 2104-2113 ◽

Cited By ~ 17

Author(s):

Sam Musallam ◽

R. D. Tomlinson

Keyword(s):

Angular Velocity ◽

Firing Rate ◽

Vestibular Nucleus ◽

Semicircular Canals ◽

Excitatory Postsynaptic Potential ◽

Otolith Organs ◽

Neural Integrator ◽

Postsynaptic Potential ◽

Translational Acceleration ◽

Vestibular Pathways

Angular and translational accelerations excite the semicircular canals and otolith organs, respectively. While canal afferents approximately encode head angular velocity due to the biomechanical integration performed by the canals, otolith signals have been found to approximate head translational acceleration. Because central vestibular pathways require velocity and position signals for their operation, the question has been raised as to how the integration of the otolith signals is accomplished. We recorded responses from 62 vestibular-only neurons in the vestibular nucleus of two monkeys to position transients in the naso-occipital and interaural orientations and varying directions in between. Responses to the transients were directionally asymmetric; one direction elicited a response that approximated the integral of the acceleration of the stimulus. In the opposite direction, the cells simply encoded the acceleration of the motion. We present a model that suggests that a neural integrator is not needed. Instead a neuron with a long membrane time constant and an excitatory postsynaptic potential duration that increases with the firing rate of the presynaptic cell can emulate the observed behavior.

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Interprovincial and interannual differences in the causes of land-use fires in Sumatra, Indonesia

Environmental Conservation ◽

10.1017/s0376892903000390 ◽

2003 ◽

Vol 30 (4) ◽

pp. 375-387 ◽

Cited By ~ 26

Author(s):

F. Stolle ◽

E.F. Lambin

Keyword(s):

Land Use ◽

Cultural Landscape ◽

Large Scale ◽

Land Allocation ◽

Temporal Association ◽

Forested Areas ◽

Production Area ◽

Factor Interactions ◽

In Fire ◽

Use Factors

Despite the vast destruction caused by recent fires in Sumatra's forested areas, there have been few analyses of their spatial variability and causes. Various combinations of predisposing and land-use factors in space and time may cause fires. For each variable, fire densities were calculated to assess the spatial and temporal association between natural and cultural landscape variables and fire occurrence in four provinces in Sumatra, Indonesia for a non-dry year (1999) and a dry year (1997). This was complemented by a single multivariate logistic regression for the two years over the four provinces with fires as the dependent variable and land use and predisposing factors as independent variables. The provincial analyses showed that fires are determined by multiple, interacting factors and that these factor interactions are not the same in all provinces. In the non-dry year, the factors were only weak determinants of fires and only few determinants were common to all provinces (presence of undisturbed forests, elevation, smallholder area, land allocation to production area). In the dry year, more determinants of fires were found to be common to all provinces (presence of undisturbed forests, elevation, land allocation to production or conversion areas, presence of plantations, distance from roads). This led to the identification of pathways that increased fire probability. The first step was the allocation of land to different land-use types and stakeholders by national policies. If allocated to large-scale landowners, fires were more likely to occur in plantations, especially in the dry year. Logging concessions did not play a major role in increasing the incidence of fire. However the strongest increase in fire probability was outside the areas under use, in undisturbed forests. We conclude that areas not yet used by large-scale landowners were more prone to fire, indicating a serious threat to the remaining forests in this region.

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