scholarly journals On the nature of time-varying functional connectivity in resting fMRI

Author(s):  
Daniel J Lurie ◽  
Daniel Kessler ◽  
Danielle S Bassett ◽  
Richard F. Betzel ◽  
Michael Breakspear ◽  
...  

The brain is a complex dynamical system composed of many interacting sub-regions. Knowledge of how these interactions reconfigure over time is critical to a full understanding of the brain’s functional architecture, the neural basis of flexible cognition and behavior, and how neural systems are disrupted in psychiatric and neurological illness. The idea that we might be able to study neural and cognitive dynamics through analysis of neuroimaging data has catalyzed substantial interest in methods which seek to estimate moment-to-moment fluctuations in functional connectivity (often referred to as “dynamic” or time-varying connectivity; TVC). At the same time, debates have emerged regarding the application of TVC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive relevance of resting TVC. These and other unresolved issues complicate the interpretation of resting TVC findings and limit the insights which can be gained from this otherwise promising research area. This article reviews the current resting TVC literature in light of these issues. We introduce core concepts, define key terms, summarize current controversies and open questions, and present a forward-looking perspective on how resting TVC analyses can be rigorously applied to investigate a wide range of questions in cognitive and systems neuroscience.

2020 ◽  
Vol 4 (1) ◽  
pp. 30-69 ◽  
Author(s):  
Daniel J. Lurie ◽  
Daniel Kessler ◽  
Danielle S. Bassett ◽  
Richard F. Betzel ◽  
Michael Breakspear ◽  
...  

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as “dynamic” or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.


2020 ◽  
Vol 10 (3) ◽  
pp. 160 ◽  
Author(s):  
Francesco Bartoli ◽  
Geoffrey Burnstock ◽  
Cristina Crocamo ◽  
Giuseppe Carrà

It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.


2019 ◽  
Author(s):  
Paulo Aparecido Amaral Júnior ◽  
Flávio Afonso Gonçalves Mourão ◽  
Mariana Chamon Ladeira Amâncio ◽  
Hyorrana Pereira Pinto ◽  
Vinícius Rezende Carvalho ◽  
...  

ABSTRACTAnimal behavioral paradigms, such as classical conditioning and operant conditioning, are an important tool to study the neural basis of cognition and behavior. These paradigms involve manipulating sensory stimuli in a way that learning processes are induced under controlled experimental conditions. However, the majority of the commercially available equipment did not offer flexibility to manipulate stimuli. Therefore, the development of most versatile devices would allow the study of more complex cognitive functions. The purpose of this work is to present a low-cost, customized and wireless-operated chamber for animal behavior conditioning, based on the joint operation of two microcontroller modules: Arduino Due and ESP8266-12E. Our results showed that the auditory stimulation system allows setting the carrier frequency in the range of 1 Hz up to more than 100 kHz and the sound stimulus can be modulated in amplitude, also over a wide range of frequencies. Likewise, foot-shock could be precisely manipulated regarding its amplitude (from ~200 μA to ~1500 μA) and frequency (up to 20 pulses per second). Finally, adult rats exposed to a protocol of cued fear conditioning in our device showed consistent behavioral response and electrophysiological evoked responses in the midbrain auditory pathway. Furthermore, the device developed in the current study represents an open source alternative to develop customized protocols to study fear memory under conditions of varied sensory stimuli.


2019 ◽  
Author(s):  
Lorenzo Pasquini ◽  
Gianina Toller ◽  
Adam Staffaroni ◽  
Jesse A. Brown ◽  
Jersey Deng ◽  
...  

AbstractThe human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity varies over time. We implemented a novel approach combining seed-to-whole-brain sliding-window functional connectivity MRI and k-means clustering to assess time-varying functional connectivity of aINS subregions. We studied three independent large samples of healthy participants and longitudinal datasets to assess inter- and intra-subject stability, and related aINS time-varying functional connectivity profiles to dispositional empathy. We identified four robust aINS time-varying functional connectivity modes that displayed both “state” and “trait” characteristics: while modes featuring connectivity to sensory regions were modulated by eye closure, modes featuring connectivity to higher cognitive and emotional processing regions were stable over time and related to empathy measures.


2019 ◽  
Author(s):  
Lionel Barnett ◽  
Suresh D. Muthukumaraswamy ◽  
Robin L. Carhart-Harris ◽  
Anil K. Seth

AbstractNeuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.


2014 ◽  
Author(s):  
Bradly Alicea

As a research tool, virtual environments hold immense promise for brain scientists. Yet to fully realize this potential in non-human systems, theoretical and conceptual perspectives must be developed. When selectively coupled to nervous systems, virtual environments can help us better understand the functional architecture of animals’ brains during naturalistic behaviors. While this will no doubt allow us to further our understanding of the neural basis of behavior, there is also an opportunity to uncover the diversity inherent in brain activity and behavior. This is due to two properties of virtual environments: the ability to create sensory illusions, and the ability to dilate space and/or time. These and other potential manipulations will be characterized as the effects of virtuality. In addition, the systems-level outcomes of virtual environment-enhanced perception will be discussed in the context of the uncanny valley and other expected relationships between emotional valence, cognition, and training. These effects and their usefulness for brain science will be understood in the context of three types of neurobehavioral phenomena: sensorimotor integration, spatial navigation, and interactivity. For each of these behaviors, a combination of illusory and space/time dilation examples will be reviewed. Once these examples are presented, the implications for improving upon virtual models for more directly inducing the mental phenomena of illusion and space/time dilation will be considered. To conclude, future directions for integrating this research area into a strategy of broader biological inquiry will be presented.


2014 ◽  
Author(s):  
Bradly Alicea

As a research tool, virtual environments hold immense promise for brain scientists. Yet to fully realize this potential in non-human systems, theoretical and conceptual perspectives must be developed. When selectively coupled to nervous systems, virtual environments can help us better understand the functional architecture of animals’ brains during naturalistic behaviors. While this will no doubt allow us to further our understanding of the neural basis of behavior, there is also an opportunity to uncover the diversity inherent in brain activity and behavior. This is due to two properties of virtual environments: the ability to create sensory illusions, and the ability to dilate space and/or time. These and other potential manipulations will be characterized as the effects of virtuality. These effects and their usefulness for brain science will be understood in the context of three types of neurobehavioral phenomena: sensorimotor integration, spatial navigation, and interactivity. For each of these behaviors, a combination of illusory and time dilation examples will be reviewed. Once these examples are presented, the implications for improving upon virtual models for more directly inducing the mental phenomena of illusion and time dilation will be considered. To conclude, future directions for integrating this research area into broader biological inquiry will be presented.


2012 ◽  
Vol 108 (2) ◽  
pp. 684-696 ◽  
Author(s):  
Zepeng Yao ◽  
Ann Marie Macara ◽  
Katherine R. Lelito ◽  
Tamara Y. Minosyan ◽  
Orie T. Shafer

Drosophila melanogaster is a valuable model system for the neural basis of complex behavior, but an inability to routinely interrogate physiologic connections within central neural networks of the fly brain remains a fundamental barrier to progress in the field. To address this problem, we have introduced a simple method of measuring functional connectivity based on the independent expression of the mammalian P2X2 purinoreceptor and genetically encoded Ca2+ and cAMP sensors within separate genetically defined subsets of neurons in the adult brain. We show that such independent expression is capable of specifically rendering defined sets of neurons excitable by pulses of bath-applied ATP in a manner compatible with high-resolution Ca2+ and cAMP imaging in putative follower neurons. Furthermore, we establish that this approach is sufficiently sensitive for the detection of excitatory and modulatory connections deep within larval and adult brains. This technically facile approach can now be used in wild-type and mutant genetic backgrounds to address functional connectivity within neuronal networks governing a wide range of complex behaviors in the fly. Furthermore, the effectiveness of this approach in the fly brain suggests that similar methods using appropriate heterologous receptors might be adopted for other widely used model systems.


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