scholarly journals Multi-sensory integration in the mouse cortical connectome using a network diffusion model

2019 ◽  
Author(s):  
Kamal Shadi ◽  
Eva Dyer ◽  
Constantine Dovrolis

AbstractHaving a structural network representation of connectivity in the brain is instrumental in analyzing communication dynamics and information processing in the brain. In this work, we make steps towards understanding multi-sensory information flow and integration using a network diffusion approach. In particular, we model the flow of evoked activity, initiated by stimuli at primary sensory regions, using the Asynchronous Linear Threshold (ALT) diffusion model. The ALT model captures how evoked activity that originates at a given region of the cortex “ripples through” other brain regions (referred to as an activation cascade). By comparing the model results to functional datasets based on Voltage Sensitive Dye (VSD) imaging, we find that in most cases the ALT model predicts the temporal ordering of an activation cascade correctly. Our results on the Mouse Connectivity Atlas from the Allen Institute for Brain Science show that a small number of brain regions are involved in many primary sensory streams – the claustrum and the parietal temporal cortex being at the top of the list. This suggests that the cortex relies on an hourglass architecture to first integrate and compress multi-sensory information from multiple sensory regions, before utilizing that lower-dimensionality representation in higher-level association regions and more complex cognitive tasks.

2020 ◽  
Vol 4 (4) ◽  
pp. 1030-1054
Author(s):  
Kamal Shadi ◽  
Eva Dyer ◽  
Constantine Dovrolis

Having a structural network representation of connectivity in the brain is instrumental in analyzing communication dynamics and neural information processing. In this work, we make steps towards understanding multisensory information flow and integration using a network diffusion approach. In particular, we model the flow of evoked activity, initiated by stimuli at primary sensory regions, using the asynchronous linear threshold (ALT) diffusion model. The ALT model captures how evoked activity that originates at a given region of the cortex “ripples through” other brain regions (referred to as an activation cascade). We find that a small number of brain regions–the claustrum and the parietal temporal cortex being at the top of the list–are involved in almost all cortical sensory streams. This suggests that the cortex relies on an hourglass architecture to first integrate and compress multisensory information from multiple sensory regions, before utilizing that lower dimensionality representation in higher level association regions and more complex cognitive tasks.


2021 ◽  
Author(s):  
Rahat Hasan ◽  
Jack Humphrey ◽  
Conceicao Bettencourt ◽  
Tammaryn Lashley ◽  
Pietro Fratta ◽  
...  

Frontotemporal lobar degeneration (FTLD) is a group of heterogeneous neurodegenerative disorders affecting the frontal and temporal lobes of the brain. Nuclear loss and cytoplasmic aggregation of the RNA-binding protein TDP-43 represents the major FTLD pathology, known as FTLD-TDP. To date, there is no effective treatment for FTLD-TDP due to an incomplete understanding of the molecular mechanisms underlying disease development. Here we compared post-mortem tissue RNA-seq transcriptomes from the frontal cortex, temporal cortex and cerebellum between 28 controls and 30 FTLD-TDP patients to profile changes in cell-type composition, gene expression and transcript usage. We observed downregulation of neuronal markers in all three regions of the brain, accompanied by upregulation of microglia, astrocytes, and oligodendrocytes, as well as endothelial cells and pericytes, suggesting shifts in both immune activation and within the vasculature. We validate our estimates of neuronal loss using neuropathological atrophy scores and show that neuronal loss in the cortex can be mainly attributed to excitatory neurons, and that increases in microglial and endothelial cell expression are highly correlated with neuronal loss. All our analyses identified a strong involvement of the cerebellum in the neurodegenerative process of FTLD-TDP. Altogether, our data provides a detailed landscape of gene expression alterations to help unravel relevant disease mechanisms in FTLD.


Author(s):  
J. Eric Ahlskog

As a prelude to the treatment chapters that follow, we need to define and describe the types of problems and symptoms encountered in DLB and PDD. The clinical picture can be quite varied: problems encountered by one person may be quite different from those encountered by another person, and symptoms that are problematic in one individual may be minimal in another. In these disorders, the Lewy neurodegenerative process potentially affects certain nervous system regions but spares others. Affected areas include thinking and memory circuits, as well as movement (motor) function and the autonomic nervous system, which regulates primary functions such as bladder, bowel, and blood pressure control. Many other brain regions, by contrast, are spared or minimally involved, such as vision and sensation. The brain and spinal cord constitute the central nervous system. The interface between the brain and spinal cord is by way of the brain stem, as shown in Figure 4.1. Thought, memory, and reasoning are primarily organized in the thick layers of cortex overlying lower brain levels. Volitional movements, such as writing, throwing, or kicking, also emanate from the cortex and integrate with circuits just below, including those in the basal ganglia, shown in Figure 4.2. The basal ganglia includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra, as illustrated in Figure 4.2. Movement information is integrated and modulated in these basal ganglia nuclei and then transmitted down the brain stem to the spinal cord. At spinal cord levels the correct sequence of muscle activation that has been programmed is accomplished. Activated nerves from appropriate regions of the spinal cord relay the signals to the proper muscles. Sensory information from the periphery (limbs) travels in the opposite direction. How are these signals transmitted? Brain cells called neurons have long, wire-like extensions that interface with other neurons, effectively making up circuits that are slightly similar to computer circuits; this is illustrated in Figure 4.3. At the end of these wire-like extensions are tiny enlargements (terminals) that contain specific biological chemicals called neurotransmitters. Neurotransmitters are released when the electrical signal travels down that neuron to the end of that wire-like process.


Insects ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 886
Author(s):  
Silvana Piersanti ◽  
Manuela Rebora ◽  
Gianandrea Salerno ◽  
Sylvia Anton

Dragonflies are hemimetabolous insects, switching from an aquatic life style as nymphs to aerial life as adults, confronted to different environmental cues. How sensory structures on the antennae and the brain regions processing the incoming information are adapted to the reception of fundamentally different sensory cues has not been investigated in hemimetabolous insects. Here we describe the antennal sensilla, the general brain structure, and the antennal sensory pathways in the last six nymphal instars of Libellula depressa, in comparison with earlier published data from adults, using scanning electron microscopy, and antennal receptor neuron and antennal lobe output neuron mass-tracing with tetramethylrhodamin. Brain structure was visualized with an anti-synapsin antibody. Differently from adults, the nymphal antennal flagellum harbors many mechanoreceptive sensilla, one olfactory, and two thermo-hygroreceptive sensilla at all investigated instars. The nymphal brain is very similar to the adult brain throughout development, despite the considerable differences in antennal sensilla and habitat. Like in adults, nymphal brains contain mushroom bodies lacking calyces and small aglomerular antennal lobes. Antennal fibers innervate the antennal lobe similar to adult brains and the gnathal ganglion more prominently than in adults. Similar brain structures are thus used in L. depressa nymphs and adults to process diverging sensory information.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xueyan Fu ◽  
Will Patterson ◽  
Gregory Dolnikowski ◽  
Bess Dawson-Hughes ◽  
Martha Morris ◽  
...  

Abstract Objectives Very little is known about the forms of vitamin D and vitamin K in the human brain. The objective of this study is to evaluate concentrations of vitamin D and vitamin K forms in human brain and their correlations across four human brain regions. Methods Vitamin D [D3, 25(OH)D and 1,25(OH)2D] and vitamin K [phylloquinone and menaquinone-4 (MK4)] concentrations were measured by LC/MS/MS and HPLC, respectively, in four brain regions from post-mortem samples obtained from participants in the Rush Memory and Aging Project (n = 130, mean age 82 yrs, 81% female). The brain regions analyzed were the mid-frontal cortex (MF) and mid-temporal cortex (MT) [two regions important for memory in Alzheimer's Disease (AD)], the cerebellum (CR, a region not affected by AD), and the anterior watershed white matter (AWS, a region associated with vascular disease). The correlations among the vitamin forms across brain regions were calculated using Spearman rank order correlation coefficients. Significance was set at P < 0.001. Results The average concentrations of vitamin D3, 25(OH)D and MK4 were 604 pg/g, 535 pg/g, and 3.4 pmol/g, respectively. 25(OH)D and MK4 were detected in >95% of the brain samples. Nearly 92% of 1,25(OH)2D and 80% of phylloquinone samples had concentrations below the limit of assay detection (LOD) 1,25(OH)2D = 20 ng/g, phylloquinone = 0.1 pmol/g). Vitamin D3 and 25(OH)D concentrations were positively correlated across all four regions (all Spearman r ≥ 0.78, P < 0.0001). The 1,25(OH)2D was significantly correlated between the MF and CR regions only (Spearman r = 0.30, P < 0.001, all other P ≥ 0.002). MK4 and PK were positively correlated across the four regions studied (MK4 all Spearman r ≥ 0.78, phylloquinone r ≥ 0.49, all P < 0.001). Conclusions To the best of our knowledge, this study is the first evaluation of the concentrations of vitamin D and vitamin K forms in multiple regions of the human brain. Overall, the vitamin D and vitamin K forms were each positively correlated across the four brain regions studied. Future studies are needed to clarify the roles of these nutrients in AD and dementia. Funding Sources National Institute of Aging.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jonghan Shin ◽  
Vladimir Kepe ◽  
Gary W. Small ◽  
Michael E. Phelps ◽  
Jorge R. Barrio

The spatial correlations between the brain's default mode network (DMN) and the brain regions known to develop pathophysiology in Alzheimer's disease (AD) have recently attracted much attention. In this paper, we compare results of different functional and structural imaging modalities, including MRI and PET, and highlight different patterns of anomalies observed within the DMN. Multitracer PET imaging in subjects with and without dementia has demonstrated that [C-11]PIB- and [F-18]FDDNP-binding patterns in patients with AD overlap within nodes of the brain's default network including the prefrontal, lateral parietal, lateral temporal, and posterior cingulate cortices, with the exception of the medial temporal cortex (especially, the hippocampus) where significant discrepancy between increased [F-18]FDDNP binding and negligible [C-11]PIB-binding was observed. [F-18]FDDNP binding in the medial temporal cortex—a key constituent of the DMN—coincides with both the presence of amyloid and tau pathology, and also with cortical areas with maximal atrophy as demonstrated by T1-weighted MR imaging of AD patients.


2019 ◽  
Vol 375 (1791) ◽  
pp. 20190304 ◽  
Author(s):  
Ryan Calmus ◽  
Benjamin Wilson ◽  
Yukiko Kikuchi ◽  
Christopher I. Petkov

Understanding how the brain forms representations of structured information distributed in time is a challenging endeavour for the neuroscientific community, requiring computationally and neurobiologically informed approaches. The neural mechanisms for segmenting continuous streams of sensory input and establishing representations of dependencies remain largely unknown, as do the transformations and computations occurring between the brain regions involved in these aspects of sequence processing. We propose a blueprint for a neurobiologically informed and informing computational model of sequence processing (entitled: Vector-symbolic Sequencing of Binding INstantiating Dependencies, or VS-BIND). This model is designed to support the transformation of serially ordered elements in sensory sequences into structured representations of bound dependencies, readily operates on multiple timescales, and encodes or decodes sequences with respect to chunked items wherever dependencies occur in time. The model integrates established vector symbolic additive and conjunctive binding operators with neurobiologically plausible oscillatory dynamics, and is compatible with modern spiking neural network simulation methods. We show that the model is capable of simulating previous findings from structured sequence processing tasks that engage fronto-temporal regions, specifying mechanistic roles for regions such as prefrontal areas 44/45 and the frontal operculum during interactions with sensory representations in temporal cortex. Finally, we are able to make predictions based on the configuration of the model alone that underscore the importance of serial position information, which requires input from time-sensitive cells, known to reside in the hippocampus and dorsolateral prefrontal cortex. This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.


2018 ◽  
Vol 29 (8) ◽  
pp. 3380-3389
Author(s):  
Timothy J Andrews ◽  
Ryan K Smith ◽  
Richard L Hoggart ◽  
Philip I N Ulrich ◽  
Andre D Gouws

Abstract Individuals from different social groups interpret the world in different ways. This study explores the neural basis of these group differences using a paradigm that simulates natural viewing conditions. Our aim was to determine if group differences could be found in sensory regions involved in the perception of the world or were evident in higher-level regions that are important for the interpretation of sensory information. We measured brain responses from 2 groups of football supporters, while they watched a video of matches between their teams. The time-course of response was then compared between individuals supporting the same (within-group) or the different (between-group) team. We found high intersubject correlations in low-level and high-level regions of the visual brain. However, these regions of the brain did not show any group differences. Regions that showed higher correlations for individuals from the same group were found in a network of frontal and subcortical brain regions. The interplay between these regions suggests a range of cognitive processes from motor control to social cognition and reward are important in the establishment of social groups. These results suggest that group differences are primarily reflected in regions involved in the evaluation and interpretation of the sensory input.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alfonso Díaz ◽  
Samuel Treviño ◽  
Jorge Guevara ◽  
Guadalupe Muñoz-Arenas ◽  
Eduardo Brambila ◽  
...  

Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.


2021 ◽  
Vol 12 ◽  
Author(s):  
João Castelhano ◽  
Gisela Lima ◽  
Marta Teixeira ◽  
Carla Soares ◽  
Marta Pais ◽  
...  

There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g., LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.


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