scholarly journals Multisensory integration in the mouse cortical connectome using a network diffusion model

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.

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.


2000 ◽  
Vol 83 (5) ◽  
pp. 3133-3139 ◽  
Author(s):  
Vincent P. Clark ◽  
Sean Fannon ◽  
Song Lai ◽  
Randall Benson ◽  
Lance Bauer

Previous studies have found that the P300 or P3 event-related potential (ERP) component is useful in the diagnosis and treatment of many disorders that influence CNS function. However, the anatomic locations of brain regions involved in this response are not precisely known. In the present event-related functional magnetic resonance imaging (fMRI) study, methods of stimulus presentation, data acquisition, and data analysis were optimized for the detection of brain activity in response to stimuli presented in the three-stimulus oddball task. This paradigm involves the interleaved, pseudorandom presentation of single block-letter target and distractor stimuli that previously were found to generate the P3b and P3a ERP subcomponents, respectively, and frequent standard stimuli. Target stimuli evoked fMRI signal increases in multiple brain regions including the thalamus, the bilateral cerebellum, and the occipital-temporal cortex as well as bilateral superior, medial, inferior frontal, inferior parietal, superior temporal, precentral, postcentral, cingulate, insular, left middle temporal, and right middle frontal gyri. Distractor stimuli evoked an fMRI signal change bilaterally in inferior anterior cingulate, medial frontal, inferior frontal, and right superior frontal gyri, with additional activity in bilateral inferior parietal lobules, lateral cerebellar hemispheres and vermis, and left fusiform, middle occipital, and superior temporal gyri. Significant variation in the amplitude and polarity of distractor-evoked activity was observed across stimulus repetitions. No overlap was observed between target- and distractor-evoked activity. These event-related fMRI results shed light on the anatomy of responses to target and distractor stimuli that have proven useful in many ERP studies of healthy and clinically impaired populations.


2020 ◽  
Author(s):  
Nicholas Parsons ◽  
Athanasia Outsikas ◽  
Annie Parish ◽  
Rebecca Clohesy ◽  
Nilam Thakkar ◽  
...  

SummaryBackgroundNeuropathology caused by the coronavirus disease 2019 (COVID-19) has been reported across several studies. The characterisation of the spatial distribution of these pathology remains critical to assess long and short-term neurological sequelae of COVID-19. To this end, Mathematical models can be used to characterise the location and aetiologies underlying COVID-19-related neuropathology.MethodWe performed a systematic review of the literature to quantify the locations of small neurological events identified with magnetic resonance imaging (MRI) among COVID-19 patients. Neurological events were localised into the Desikan-Killiany grey and white matter atlases. A mathematical network diffusion model was then used to test whether the spatial distribution of neurological events could be explained via a linear spread through the structural connectome of the brain.FindingsWe identified 35 articles consisting of 123 patients that assessed the spatial distribution of small neurological events among COVID-19 patients. Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds. White matter events were observed within 14 of 42 white matter bundles from the IIT atlas. The highest proportions (26%) of events were observed within the bilateral corticospinal tracts. The splenium and middle of the corpus callosum were affected in 14% and 9% of the cases respectively. Grey matter events were spatially distributed in the 41 brain regions within the Desikan-Killiany atlas. The highest proportions (∼10%) of the events were observed in areas including the bilateral superior temporal, precentral, and lateral occipital cortices. Sub-cortical events were most frequently identified in the Pallidum. The application of a mathematical network diffusion model suggested that the spatial pattern of the small neurological events in COVID-19 can be modelled with a linear diffusion of spread from epicentres in the bilateral cerebellum and basal ganglia (Pearson’s r=0.41, p<0.001, corrected).InterpretationTo our knowledge, this is the first study to systematically characterise the spatial distribution of small neurological events in COVID-19 patients and test whether the spatial distribution of these events can be explained by a linear diffusion spread model. The location of neurological events is consistent with commonly identified neurological symptoms including alterations in conscious state among COVID-19 patients that require brain imaging. Given the prevalence and severity of these manifestations, clinicians should carefully monitor neurological symptoms within COVID-19 patients and their potential long-term sequelae.


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.


2019 ◽  
Vol 30 (3) ◽  
pp. 875-887
Author(s):  
Kai Hwang ◽  
James M Shine ◽  
Dillan Cellier ◽  
Mark D’Esposito

Abstract Past studies have demonstrated that flexible interactions between brain regions support a wide range of goal-directed behaviors. However, the neural mechanisms that underlie adaptive communication between brain regions are not well understood. In this study, we combined theta-burst transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging to investigate the sources of top-down biasing signals that influence task-evoked functional connectivity. Subjects viewed sequences of images of faces and buildings and were required to detect repetitions (2-back vs. 1-back) of the attended stimuli category (faces or buildings). We found that functional connectivity between ventral temporal cortex and the primary visual cortex (VC) increased during processing of task-relevant stimuli, especially during higher memory loads. Furthermore, the strength of functional connectivity was greater for correct trials. Increases in task-evoked functional connectivity strength were correlated with increases in activity in multiple frontal, parietal, and subcortical (caudate and thalamus) regions. Finally, we found that TMS to superior intraparietal sulcus (IPS), but not to primary somatosensory cortex, decreased task-specific modulation in connectivity patterns between the primary VC and the parahippocampal place area. These findings demonstrate that the human IPS is a source of top-down biasing signals that modulate task-evoked functional connectivity among task-relevant cortical regions.


Author(s):  
D.G. Walker ◽  
B.E. Boyes ◽  
P.L. McGeer ◽  
E.G. McGeer

ABSTRACT:The pathological changes that occur in Alzheimer disease (AD) brain lead to a large loss of various classes of neurons and the production of novel proteinaceous elements such as neuritic plaques and neurofibrillary tangles. For the neuronal loss to occur and these elements to arise, there must be a disturbance in the expression or regulation of genes that code for proteins required for normal cell maintenance, or perhaps even for the expression of genes unique to AD. We describe the construction of a cDNA library from the human substantia innominata and strategies for isolating genes that are expressed differentially between brain regions and which may be affected by AD. Some of the results obtained using these strategies and a preliminary description of a novel brain specific mRNA of 15.5kb, whose expression is increased in AD affected temporal cortex, are presented.


2019 ◽  
Vol 51 (3) ◽  
pp. 155-166
Author(s):  
Annamaria Painold ◽  
Pascal L. Faber ◽  
Eva Z. Reininghaus ◽  
Sabrina Mörkl ◽  
Anna K. Holl ◽  
...  

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired t tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients.


2019 ◽  
Vol 12 ◽  
pp. 175628641988066 ◽  
Author(s):  
Venkata C. Chirumamilla ◽  
Christian Dresel ◽  
Nabin Koirala ◽  
Gabriel Gonzalez-Escamilla ◽  
Günther Deuschl ◽  
...  

Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minimal clinical symptom representation, and HC at baseline. Group regional cross-correlation matrices calculated based on grey matter volume were included in graph-based network analysis. We used these to quantify global network measures of segregation and integration, and also looked at local connectivity properties of different brain regions. Results: The networks in patients with BSP were more segregated than in patients with HFS and HC ( p < 0.001). BSP patients had increased connectivity in frontal and temporal cortices, including sensorimotor cortex, and reduced connectivity in the cerebellum, relative to both HFS patients and HC ( p < 0.05). Compared with HC, HFS patients showed increased connectivity in temporal and parietal cortices and a decreased connectivity in the frontal cortex ( p < 0.05). In BSP patients, the connectivity of the frontal cortex diminished after BoNT treatment ( p < 0.05). In contrast, HFS patients showed increased connectivity in the temporal cortex and reduced connectivity in cerebellum after BoNT treatment ( p < 0.05). Conclusions: Our results show that BSP patients display alterations in both segregation and integration in the brain at the network level. The regional differences identified in the sensorimotor cortex and cerebellum of these patients may play a role in the pathophysiology of focal dystonia. Moreover, symptomatic reduction of hyperkinesia by BoNT treatment was associated with different brain network fingerprints in both BSP and HFS patients.


2019 ◽  
Vol 16 (11) ◽  
pp. 1055-1062
Author(s):  
Xi Sun ◽  
Binbin Nie ◽  
Shujun Zhao ◽  
Qian Chen ◽  
Panlong Li ◽  
...  

Background: Visuospatial dysfunction is one predominant symptom in many atypical Alzheimer’s disease (AD) patients, however, until now its neural correlates still remain unclear. For the accumulation of intracellular hyperphosphorylated tau proteins is a major pathogenic factor in neurodegeneration of AD, the distributional pattern of tau could highlight the affected brain regions associated with specific cognitive deficits. Objective: We investigated the brain regions particularly affected by tau accumulation in patients with visuospatial dysfunction to explore its neural correlates. Methods: Using 18F-AV-1451 tau positron emission tomography (PET), voxel-wise two-sample t-tests were performed between AD patients with obvious visuospatial dysfunction (VS-AD) and cognitively normal subjects, AD patients with little-to-no visuospatial dysfunction (non VS-AD) and cognitively normal subjects, respectively. Results: Results showed increased tau accumulations mainly located in occipitoparietal cortex, posterior cingulate cortex, precuneus, inferior and medial temporal cortex in VS-AD patients, while increased tau accumulations mainly occurred in the inferior and medial temporal cortex in non VS-AD patients. Conclusion: These findings suggested that occipitoparietal cortex, posterior cingulate cortex and precuneus, which were particularly affected by increased tau accumulation in VS-AD patients, may associate with visuospatial dysfunction of AD.


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.


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