scholarly journals Title: Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal

2016 ◽  
Author(s):  
Yu-Rong Gao ◽  
Yuncong Ma ◽  
Qingguang Zhang ◽  
Aaron T. Winder ◽  
Zhifeng Liang ◽  
...  
Keyword(s):  
Animal Models ◽  
Neural Activity ◽  
Neurovascular Coupling ◽  
Quantitative Relationship ◽  
Extensive Study ◽  
Blood Oxygenation ◽  
Oxygenation Level ◽  
Brain Circuit ◽  
Circuit Function ◽  
Awake Animal

AbstractFunctional magnetic resonance imaging (fMRI) has allowed the noninvasive study of task-based and resting-state brain dynamics in humans by inferring neural activity from blood-oxygenation-level dependent (BOLD) signal changes. An accurate interpretation of the hemodynamic changes that underlie fMRI signals depends on the understanding of the quantitative relationship between changes in neural activity and changes in cerebral blood flow, oxygenation and volume. While there has been extensive study of neurovascular coupling in anesthetized animal models, anesthesia causes large disruptions of brain metabolism, neural responsiveness and cardiovascular function. Here, we review work showing that neurovascular coupling and brain circuit function in the awake animal are profoundly different from those in the anesthetized state. We argue that the time is right to study neurovascular coupling and brain circuit function in the awake animal to bridge the physiological mechanisms that underlie animal and human neuroimaging signals, and to interpret them in light of underlying neural mechanisms. Lastly, we discuss recent experimental innovations that have enabled the study of neurovascular coupling and brain-wide circuit function in un-anesthetized and behaving animal models.

scholarly journals Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals

2002 ◽  
Vol 22 (8) ◽  
pp. 908-917 ◽  
Author(s):  
Noam Harel ◽  
Sang-Pil Lee ◽  
Tsukasa Nagaoka ◽  
Dae-Shik Kim ◽  
Seong-Gi Kim
Keyword(s):  
Neural Activity ◽  
Spike Activity ◽  
Visual Stimulation ◽  
Blood Oxygenation Level Dependent ◽  
Blood Oxygenation ◽  
Bold Signal ◽  
Area 18 ◽  
Blood Oxygenation Level ◽  
Oxygenation Level ◽  
Negative Bold

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level—dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the postitive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

scholarly journals A multi-data based quantitative model for neurovascular coupling in the brain.

2021 ◽  
Author(s):  
Sebastian Sten ◽  
Henrik Podéus ◽  
Nicolas Sundqvist ◽  
Fredrik Elinder ◽  
Maria Engström ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Neurovascular Coupling ◽  
Quantitative Model ◽  
Blood Oxygenation ◽  
Data Types ◽  
Hemodynamic Changes ◽  
Validation Data ◽  
The Core ◽  
Oxygenation Level ◽  
The Brain

The neurovascular coupling (NVC) forms the foundation for functional imaging techniques of the brain, since NVC connects neural activity with observable hemodynamic changes. Many aspects of the NVC have been studied both experimentally and with mathematical models: various combinations of blood volume and flow, electrical activity, oxygen saturation measures, blood oxygenation level-dependent (BOLD) response, and optogenetics have been measured and modeled in rodents, primates, or humans. We now present a first inter-connected mathematical model that describes all such data types simultaneously. The model can predict independent validation data not used for training. Using simulations, we show for example how complex bimodal behaviors appear upon stimulation. These simulations thus demonstrate how our new quantitative model, incorporating most of the core aspects of the NVC, can be used to mechanistically explain each of its constituent datasets.

scholarly journals Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190623
Author(s):  
Mitsuhiro Fukuda ◽  
Alexander J. Poplawsky ◽  
Seong-Gi Kim
Keyword(s):  
High Resolution ◽  
Neuronal Activity ◽  
Cerebral Blood Volume ◽  
Functional Neuroimaging ◽  
Neurovascular Coupling ◽  
Blood Oxygenation ◽  
Non Invasive ◽  
True Location ◽  
Oxygenation Level ◽  
Spatial Specificity

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

scholarly journals Visualization of Altered Neurovascular Coupling in Chronic Stroke Patients using Multimodal Functional MRI

2012 ◽  
Vol 32 (11) ◽  
pp. 2044-2054 ◽  
Author(s):  
Jakob U Blicher ◽  
Charlotte J Stagg ◽  
Jacinta O'Shea ◽  
Leif Østergaard ◽  
Bradley J MacIntosh ◽  
...  
Keyword(s):  
Motor Impairment ◽  
Neurovascular Coupling ◽  
Chronic Stroke ◽  
Blood Oxygenation ◽  
Cortical Reorganization ◽  
Motor Tasks ◽  
Stroke Patients ◽  
Bold Responses ◽  
Oxygenation Level ◽  
Crucial Information

Evaluation of cortical reorganization in chronic stroke patients requires methods to accurately localize regions of neuronal activity. Blood oxygenation level-dependent ( BOLD) functional magnetic resonance imaging (fMRI) is frequently employed; however, BOLD contrast depends on specific coupling relationships between the cerebral metabolic rate of oxygen ( CMRO2), cerebral blood flow ( CBF), and volume ( CBV), which may not exist following stroke. The aim of this study was to understand whether CSF-weighted ( CBFw) and CSV-weighted ( CBVw) fMRI could be used in sequence with BOLD to characterize neurovascular coupling mechanisms poststroke. Chronic stroke patients ( n = 11) with motor impairment and age-matched controls ( n = 11) performed four sets of unilateral motor tasks (60 seconds/30 seconds off/on) during CBFw, CBVw, and BOLD fMRI acquisition. While control participants elicited mean BOLD, CBFw, and CBVw responses in motor cortex ( P < 0.01), patients showed only mean changes in CBF ( P < 0.01) and CBV ( P < 0.01), but absent mean BOLD responses ( P = 0.20). BOLD intersubject variability was consistent with differing coupling indices between CBF, CBV, and CMRO2. Thus, CBFw and/or CBVw fMRI may provide crucial information not apparent from BOLD in these patients. A table is provided outlining distinct vascular and metabolic uncoupling possibilities that elicit different BOLD responses, and the strengths and limitations of the multimodal protocol are summarized.

scholarly journals Negative BOLD-fMRI Signals in Large Cerebral Veins

2010 ◽  
Vol 31 (2) ◽  
pp. 401-412 ◽  
Author(s):  
Marta Bianciardi ◽  
Masaki Fukunaga ◽  
Peter van Gelderen ◽  
Jacco A de Zwart ◽  
Jeff H Duyn
Keyword(s):  
High Resolution ◽  
Blood Volume ◽  
Neural Activity ◽  
Blood Oxygenation ◽  
Cerebral Veins ◽  
Hemodynamic Changes ◽  
Theoretical Predictions ◽  
Oxygenation Level ◽  
Negative Bold ◽  
Task Activation

Reductions in blood oxygenation level dependent (BOLD)-functional magnetic resonance imaging (fMRI) signals below baseline levels have been observed under several conditions as negative activation in task-activation studies or anticorrelation in resting-state experiments. Converging evidence suggests that negative BOLD signals (NBSs) can generally be explained by local reductions in neural activity. Here, we report on NBSs that accompany hemodynamic changes in regions devoid of neural tissue. The NBSs were investigated with high-resolution studies of the visual cortex (VC) at 7T. Task-activation studies were performed to localize a task-positive area in the VC. During rest, robust negative correlation with the task-positive region was observed in focal regions near the ventricles and dispersed throughout the VC. Both positive and NBSs were dependent on behavioral condition. Comparison with high-resolution structural images showed that negatively correlated regions overlapped with larger pial and ependymal veins near sulcal and ventricular cerebrospinal fluid (CSF). Results from multiecho fMRI showed that NBSs were consistent with increases in local blood volume. These findings confirm theoretical predictions that tie neural activity to blood volume increases, which tend to counteract positive fMRI signal changes associated with increased blood oxygenation. This effect may be more salient in high-resolution studies, in which positive and NBS may be more often spatially distinct.

scholarly journals Detection of synchronous brain activity in white matter tracts at rest and under functional loading

2017 ◽  
Vol 115 (3) ◽  
pp. 595-600 ◽  
Author(s):  
Zhaohua Ding ◽  
Yali Huang ◽  
Stephen K. Bailey ◽  
Yurui Gao ◽  
Laurie E. Cutting ◽  
...  
Keyword(s):  
White Matter ◽  
Neural Activity ◽  
Resting State ◽  
Brain Activity ◽  
Blood Oxygenation ◽  
Task Specificity ◽  
Temporal Correlations ◽  
Neural Activities ◽  
Oxygenation Level ◽  
Functional Loading

Functional MRI based on blood oxygenation level-dependent (BOLD) contrast is well established as a neuroimaging technique for detecting neural activity in the cortex of the human brain. While detection and characterization of BOLD signals, as well as their electrophysiological and hemodynamic/metabolic origins, have been extensively studied in gray matter (GM), the detection and interpretation of BOLD signals in white matter (WM) remain controversial. We have previously observed that BOLD signals in a resting state reveal structure-specific anisotropic temporal correlations in WM and that external stimuli alter these correlations and permit visualization of task-specific fiber pathways, suggesting variations in WM BOLD signals are related to neural activity. In this study, we provide further strong evidence that BOLD signals in WM reflect neural activities both in a resting state and under functional loading. We demonstrate that BOLD signal waveforms in stimulus-relevant WM pathways are synchronous with the applied stimuli but with various degrees of time delay and that signals in WM pathways exhibit clear task specificity. Furthermore, resting-state signal fluctuations in WM tracts show significant correlations with specific parcellated GM volumes. These observations support the notion that neural activities are encoded in WM circuits similarly to cortical responses.

scholarly journals Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent “Resting-State” Connectivity

Neuron ◽  
2017 ◽  
Vol 96 (4) ◽  
pp. 936-948.e3 ◽  
Author(s):  
Celine Mateo ◽  
Per M. Knutsen ◽  
Philbert S. Tsai ◽  
Andy Y. Shih ◽  
David Kleinfeld
Keyword(s):  
Neural Activity ◽  
Resting State ◽  
Blood Oxygenation Level Dependent ◽  
Blood Oxygenation ◽  
Blood Oxygenation Level ◽  
Oxygenation Level ◽  
Resting State Connectivity

scholarly journals Noninvasive Study of Neurovascular Coupling during Graded Neuronal Suppression

2007 ◽  
Vol 28 (2) ◽  
pp. 280-290 ◽  
Author(s):  
Nanyin Zhang ◽  
Zhongming Liu ◽  
Bin He ◽  
Wei Chen
Keyword(s):  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Neurovascular Coupling ◽  
Blood Oxygenation ◽  
Experimental Session ◽  
Paired Stimulus ◽  
Neuronal Excitation ◽  
Coupling Relationship ◽  
Oxygenation Level ◽  
Excitation Conditions

In this study, the neurovascular coupling relationship was noninvasively studied in the human visual cortex. Graded neuronal/hemodynamic suppression conditions were generated using a paired-stimulus paradigm. Visual evoked potential was measured to quantify neuronal activity. Hemodynamic activities were measured and quantified by perfusion and blood oxygenation level-dependent changes. All quantification was normalized to the same activation condition induced by a single stimulus paradigm within each experimental session. This experiment design eliminated the confounding factors such as anesthesia and inconsistent neurovascular coupling patterns within and/or among tasks. The results reveal that (i) there is a tight neurovascular coupling at graded neuronal suppression conditions; (ii) the neurovascular coupling relationship contains a subtle, but significant, nonlinear component; and (iii) the linear model, nevertheless, is still a good approximation reflecting the neurovascular coupling relationship. This study extends the range of the neurovascular coupling relationship from graded neuronal excitation conditions to graded neuronal suppression conditions.

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