scholarly journals Brainstem modulation of large-scale intrinsic cortical activity correlations

2019 ◽  
Author(s):  
Ruud L. van den Brink ◽  
Thomas Pfeffer ◽  
Tobias Donner

Brain activity fluctuates continuously, even in the absence of changes in sensory input or motor output. These intrinsic activity fluctuations are correlated across brain regions and are spatially organized in macroscale networks. Variations in the strength, topography, and topology of correlated activity occur over time, and unfold upon a backbone of long-range anatomical connections. Subcortical neuromodulatory systems send widespread ascending projections to the cortex, and are thus ideally situated to shape the temporal and spatial structure of intrinsic correlations. These systems are also the targets of the pharmacological treatment of major neurological and psychiatric disorders, such as Parkinson’s disease, depression, and schizophrenia. Here, we review recent work that has investigated how neuromodulatory systems shape correlations of intrinsic fluctuations of large-scale cortical activity. We discuss studies in the human, monkey, and rodent brain, with a focus on non-invasive recordings of human brain activity. We provide a structured but selective overview of this work and distill a number of emerging principles. Future efforts to chart the effect of specific neuromodulators and, in particular, specific receptors, on intrinsic correlations may help identify shared or antagonistic principles between different neuromodulatory systems. Such principles can inform models of healthy brain function and may provide an important reference for understanding altered cortical dynamics that are evident in neurological and psychiatric disorders, potentially paving the way for mechanistically-inspired biomarkers and individualized treatments of these disorders.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongyi Zhang ◽  
Xiaowei Zhan ◽  
Bo Li

AbstractSimilarity in T-cell receptor (TCR) sequences implies shared antigen specificity between receptors, and could be used to discover novel therapeutic targets. However, existing methods that cluster T-cell receptor sequences by similarity are computationally inefficient, making them impractical to use on the ever-expanding datasets of the immune repertoire. Here, we developed GIANA (Geometric Isometry-based TCR AligNment Algorithm) a computationally efficient tool for this task that provides the same level of clustering specificity as TCRdist at 600 times its speed, and without sacrificing accuracy. GIANA also allows the rapid query of large reference cohorts within minutes. Using GIANA to cluster large-scale TCR datasets provides candidate disease-specific receptors, and provides a new solution to repertoire classification. Querying unseen TCR-seq samples against an existing reference differentiates samples from patients across various cohorts associated with cancer, infectious and autoimmune disease. Our results demonstrate how GIANA could be used as the basis for a TCR-based non-invasive multi-disease diagnostic platform.


2020 ◽  
Vol 26 (4) ◽  
pp. 343-358
Author(s):  
Giulio Rocchi ◽  
Bruno Sterlini ◽  
Samuele Tardito ◽  
Matilde Inglese ◽  
Anna Corradi ◽  
...  

The opioidergic system and intrinsic brain activity, as organized in large-scale networks such as the salience network (SN), sensorimotor network (SMN), and default-mode network (DMN), play core roles in healthy behavior and psychiatric disorders. This work aimed to investigate how opioidergic signaling affects intrinsic brain activity in healthy individuals by reviewing relevant neuroanatomical, molecular, functional, and pharmacological magnetic resonance imaging studies in order to clarify their physiological links and changes in psychiatric disorders. The SN shows dense opioidergic innervations of subcortical structures and high expression levels of opioid receptors in subcortical-cortical areas, with enhanced or reduced activity with low or very high doses of opioids, respectively. The SMN shows high levels of opioid receptors in subcortical areas and functional disconnection caused by opioids. The DMN shows low levels of opioid receptors in cortical areas and inhibited or enhanced activity with low or high doses of opioids, respectively. Finally, we proposed a working model. Opioidergic signaling enhances SN and suppresses SMN (and DMN) activity, resulting in affective excitation with psychomotor inhibition; stronger increases in opioidergic signaling attenuate the SN and SMN while disinhibiting the DMN, dissociating affective and psychomotor functions from the internal states; the opposite occurs with a deficit of opioidergic signaling.


Author(s):  
Hana Burianová

Determining the mechanisms that underlie neurocognitive aging, such as compensation or dedifferentiation, and facilitating the development of effective strategies for cognitive improvement is essential due to the steadily rising aging population. One approach to study the characteristics of healthy aging comprises the assessment of functional connectivity, delineating markers of age-related neurocognitive plasticity. Functional connectivity paradigms characterize complex one-to-many (or many-to-many) structure–function relations, as higher-level cognitive processes are mediated by the interaction among a number of functionally related neural areas rather than localized to discrete brain regions. Task-related or resting-state interregional correlations of brain activity have been used as reliable indices of functional connectivity, delineating age-related alterations in a number of large-scale brain networks, which subserve attention, working memory, episodic retrieval, and task-switching. Together with behavioral and regional activation studies, connectivity studies and modeling approaches have contributed to our understanding of the mechanisms of age-related reorganization of distributed functional networks; specifically, reduced neural specificity (dedifferentiation) and associated impairment in inhibitory control and compensatory neural recruitment.


2019 ◽  
Vol 30 (3) ◽  
pp. 1716-1734 ◽  
Author(s):  
Ryan V Raut ◽  
Anish Mitra ◽  
Scott Marek ◽  
Mario Ortega ◽  
Abraham Z Snyder ◽  
...  

Abstract Spontaneous infra-slow (<0.1 Hz) fluctuations in functional magnetic resonance imaging (fMRI) signals are temporally correlated within large-scale functional brain networks, motivating their use for mapping systems-level brain organization. However, recent electrophysiological and hemodynamic evidence suggest state-dependent propagation of infra-slow fluctuations, implying a functional role for ongoing infra-slow activity. Crucially, the study of infra-slow temporal lag structure has thus far been limited to large groups, as analyzing propagation delays requires extensive data averaging to overcome sampling variability. Here, we use resting-state fMRI data from 11 extensively-sampled individuals to characterize lag structure at the individual level. In addition to stable individual-specific features, we find spatiotemporal topographies in each subject similar to the group average. Notably, we find a set of early regions that are common to all individuals, are preferentially positioned proximal to multiple functional networks, and overlap with brain regions known to respond to diverse behavioral tasks—altogether consistent with a hypothesized ability to broadly influence cortical excitability. Our findings suggest that, like correlation structure, temporal lag structure is a fundamental organizational property of resting-state infra-slow activity.


Author(s):  
Christine Beauchene ◽  
Alexander Leonessa ◽  
Subhradeep Roy ◽  
James Simon ◽  
Nicole Abaid

The brain is a highly complex network and analyzing brain connectivity is a nontrivial task. Consequently, the neuroscience community created a large-scale, customizable, mathematical model which simulates brain activity called The Virtual Brain (TVB). Using TVB, we seek to control electroencephalography (EEG) measured brain states using auditory inputs, through TVB. A safe non-invasive brain stimulation method is binaural beats (BB) which arise from the brain’s interpretation of two pure tones, with a small frequency mismatch, delivered independently to each ear. A third phantom BB, whose frequency is equal to the difference of the two presented tones, is produced. This paper details the development and proof-of-concept testing of a simulation environment for an EEG-based closed-loop control of TVB using BB. Results suggest that the connectivity networks, constructed from simulated EEG, may change with certain BB stimulation frequency. In this work, we demonstrate that a linear controller can successfully modulate TVB connectivity.


2014 ◽  
Vol 369 (1641) ◽  
pp. 20130534 ◽  
Author(s):  
Theofanis I. Panagiotaropoulos ◽  
Vishal Kapoor ◽  
Nikos K. Logothetis

The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness , are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.


2018 ◽  
Author(s):  
Nicholas Michelson ◽  
Federico Bolaños ◽  
Luis Bolaños ◽  
Matilde Balbi ◽  
Jeffrey M LeDue ◽  
...  

We employ cortical mesoscale calcium-imaging to observe brain activity in two head-fixed mice in a staged social touch-like interaction. Using a rail system, mice are brought together to a distance where macrovibrissae of each mouse make contact. Cortical signals were recorded from both mice simultaneously before, during, and after the social contact period. When the mice were together, we observed bouts of mutual whisking and cross-mouse correlated cortical activity in the vibrissae cortex. This correlated activity was specific to individual interactions as the correlations fell in trial-shuffled mouse pairs. Whisk-related global GCAMP6s signals were greater in cagemate pairs during the together period. The effects of social interaction extend outside of regions associated with mutual touch and had global synchronizing effects on cortical activity. We present an open-source platform to investigate the neurobiology of social interaction by including mechanical drawings, protocols, and software necessary for others to extend this work.


2018 ◽  
Author(s):  
Wolfgang M. Pauli

AbstractBehavioral neuroscience has made great strides in developing animal models of human behavior and psychiatric disorders. Animal models allow for the formulation of hypotheses regarding the mechanisms underlying psychiatric disorders, and the opportunity to test these hypotheses using procedures that are too invasive for human participants. However, recent scientific reviews have highlighted the low success rate of translating results from animal models into clinical interventions in humans. A potential roadblock is that bidirectional functional mappings between the human and rodent brain are incomplete. To narrow this gap, we created a framework, Neurobabel, for performing large-scale automated synthesis of human neuroimaging data and behavioral neuroscience data. By leveraging the semantics of how researchers within each field describe their studies, this framework enables region to region mapping of brain regions across species, as well as cross-species mapping of psychological functions. As a proof of concept, we utilize the framework to create a functional cross-species mapping between the amygdala and hippocampus for fear-related and spatial memories, respectively. We then proceed to address two open questions in the field: (1) Do rodents have a dorsolateral prefrontal cortex? (2) Which human brain region corresponds to the rodent prelimbic cortex?


2021 ◽  
Vol 7 (29) ◽  
pp. eabf2513
Author(s):  
Luke J. Hearne ◽  
Ravi D. Mill ◽  
Brian P. Keane ◽  
Grega Repovš ◽  
Alan Anticevic ◽  
...  

Cognitive dysfunction is a core feature of many brain disorders, including schizophrenia (SZ), and has been linked to aberrant brain activations. However, it is unclear how these activation abnormalities emerge. We propose that aberrant flow of brain activity across functional connectivity (FC) pathways leads to altered activations that produce cognitive dysfunction in SZ. We tested this hypothesis using activity flow mapping, an approach that models the movement of task-related activity between brain regions as a function of FC. Using functional magnetic resonance imaging data from SZ individuals and healthy controls during a working memory task, we found that activity flow models accurately predict aberrant cognitive activations across multiple brain networks. Within the same framework, we simulated a connectivity-based clinical intervention, predicting specific treatments that normalized brain activations and behavior in patients. Our results suggest that dysfunctional task-evoked activity flow is a large-scale network mechanism contributing to cognitive dysfunction in SZ.


2020 ◽  
Author(s):  
Julien Vezoli ◽  
Martin Vinck ◽  
Conrado A. Bosman ◽  
Andre M. Bastos ◽  
Christopher M Lewis ◽  
...  

What is the relationship between anatomical connection strength and rhythmic synchronization? Simultaneous recordings of 15 cortical areas in two macaque monkeys show that interareal networks are functionally organized in spatially distinct modules with specific synchronization frequencies, i.e. frequency-specific functional connectomes. We relate the functional interactions between 91 area pairs to their anatomical connection strength defined in a separate cohort of twenty six subjects. This reveals that anatomical connection strength predicts rhythmic synchronization and vice-versa, in a manner that is specific for frequency bands and for the feedforward versus feedback direction, even if interareal distances are taken into account. These results further our understanding of structure-function relationships in large-scale networks covering different modality-specific brain regions and provide strong constraints on mechanistic models of brain function. Because this approach can be adapted to non-invasive techniques, it promises to open new perspectives on the functional organization of the human brain.


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